RARE DISEASE
Follicular lymphoma
Follicular lymphoma
Follicular lymphoma
Drug discovery
67
drugs
With orphan designations
Overview
Follicular Lymphoma (FL) is an indolent B-cell non-Hodgkin lymphoma characterized by slow progression, frequent relapses, and incurability. It primarily affects older adults (median age 60–65) and is often diagnosed at advanced stages (III/IV). FL involves CD20+ B-cells with chromosomal t(14;18) translocations in 85% of cases, driving BCL2 overexpression [1][7][12]. Treatment strategies range from watchful waiting for asymptomatic patients to chemoimmunotherapy, targeted therapies (e.g., PI3K/EZH2 inhibitors), and emerging immunotherapies (e.g., CAR-T) [3][5][8]. The 5-year relative survival is 89.9%, but disease burden escalates with later treatment lines [2][4][9].
Burden
Clinical: 34% mortality at 3-year follow-up for ≥3L therapy; 20% experience early progression (POD24) [4][9][14].
Treatment lines: 66% receive ≥2 lines, 34% ≥3 lines over 20 years [9][19].
Economic: Mean annual costs rise to €22,230/patient with later lines, driven by hospitalizations and novel therapies [4][14].
Therapies
Categories: rare hematological diseases, rare neoplastic diseases, rare transplant-related disorders
Research Papers
3,432 drug discovery papers about Follicular lymphoma, with 1 first-in-class and 16 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
3,432 drug discovery papers about Follicular lymphoma, with 1 first-in-class and 16 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-08-13 | Follicular Lymphoma Arising in an Ileal Neobladder Presenting as a Large Pelvic Mass.
Secondary malignancies arising in intestinal segments used for urinary diversion are rare, and reports of malignant lymphoma are extremely limited. We report a rare case of follicular lymphoma arising in an ileal neobladder 20 years after radical cystectomy. An 81-year-old man had undergone radical cystectomy with ileal neobladder reconstruction for muscle-invasive bladder cancer (pT2bN0M0) 20 years earlier and had remained recurrence-free. Follow-up imaging incidentally revealed a large pelvic mass contiguous with the neobladder and multiple enlarged lymph nodes. Transurethral resection led to a diagnosis of follicular lymphoma. Treatment with bendamustine plus rituximab achieved marked tumor reduction without severe adverse events. Malignant lymphoma arising in urinary diversion organs is extremely rare. This case highlights the potential for late-onset lymphoid malignancies following urinary diversion and emphasizes the need for long-term clinical awareness of secondary malignancies in such patients.
2026-07-28 | A Multi-Targeted Strategy for Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma: Real-World Outcomes of the ViPOR Regimen.
Background/Objectives: Relapsed/refractory (R/R) B-cell non-Hodgkin lymphomas (B-NHLs) remain a major therapeutic challenge, particularly in patients with aggressive subtypes and limited treatment options after multiple lines of therapy. The ViPOR regimen, a multi-targeted combination of venetoclax, ibrutinib, prednisone, obinutuzumab, and lenalidomide, has demonstrated promising activity in early-phase studies; however, real-world data are limited. Methods: We conducted a retrospective, two-center study including patients with R/R B-NHL treated with the ViPOR regimen between January 2024 and April 2026. Clinical characteristics, treatment responses, survival outcomes, and safety data were analyzed. Results: A total of 14 patients were included, with a median age of 45 years and a median of 3.5 prior lines of therapy. Most patients had advanced-stage disease (71% stage IV), and 36% had primary refractory disease. The interim overall response rate (ORR) was 62%, including 31% complete response (CR) and 31% partial response. At the end of treatment, the ORR was 54%, with a CR rate of 54%. Radiotherapy was incorporated in selected patients with residual disease and contributed to response deepening. Six patients (43%) were successfully bridged to allogeneic stem cell transplantation, all in CR. Responses were notably more favorable in the activated B-cell (ABC) subtype compared to the germinal center subtype. The most common adverse events were neutropenia (57%) and diarrhea (36%), and the regimen demonstrated a manageable safety profile. During follow-up, 57% of patients remained alive. Conclusions: The ViPOR regimen demonstrated promising efficacy and acceptable safety in heavily pretreated R/R B-NHL, particularly in the ABC subtype. Its ability to induce deep responses and enable bridging to allogeneic stem cell transplantation highlights its potential role in real-world clinical practice. Larger prospective studies are warranted to confirm these findings.
2026-07-26 | Covalent Bruton's tyrosine kinase inhibitor HZ-A-018 in patients with relapsed or refractory B cell malignancies: A multicenter phase I study.
HZ-A-018 represents a highly selective, covalent, novel inhibitor targeting Bruton's tyrosine kinase (BTK). This multicenter, open-label phase I study enrolled 32 patients with relapsed/refractory B cell malignancies (including diffuse large B cell lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma, Waldenström macroglobulinemia, follicular lymphoma, mantle cell lymphoma, and marginal zone lymphoma) in dose-escalation and -expansion phases. Thirty-one patients received treatment: 15 in the dose-escalation phase (75-550 mg once daily) and 16 in the expansion phase (300 mg once daily). No dose-limiting toxicities or maximum tolerated dose were identified. The most common treatment-emergent adverse events included cytopenias, rash, and hypertension. Among 29 efficacy-evaluable patients, with a median follow-up of 4.9 months, the overall response rate was 44.8%. Pharmacokinetics revealed dose-proportional exposure, and median BTK occupancy in peripheral blood mononuclear cells surpassed 95% across all dose levels at steady state. HZ-A-018 demonstrated acceptable safety and antitumor activity, supporting further clinical development.
2026-07-23 | Epigenetic and Non-Epigenetic Functions of EZH2 in Tumor Development: Structural Basis, Signaling Network, and Targeted Intervention Strategies.
Enhancer of Zeste Homolog 2 (EZH2) is a histone methyltransferase that catalyzes the methylation of histone H3 lysine 27, a modification frequently dysregulated in various cancers. EZH2 plays critical roles in cell proliferation, differentiation, and gene silencing, and its abnormal overexpression is closely associated with tumor aggressiveness and poor prognosis. Inhibiting EZH2 can reactivate tumor suppressor genes and thereby suppress cancer cell growth and metastasis. Although several EZH2 inhibitors, including small molecules and nucleic acid drugs, have been developed and some have entered clinical trials, their specificity and potency still require further optimization. Tazemetostat is the first FDA-approved EZH2 inhibitor for relapsed or refractory follicular lymphoma, while other agents such as EPZ-6438 and GSK126 show promising preclinical antitumor activity. This review summarizes the association between EZH2 and tumors, and the mechanisms and pharmacological properties of EZH2 inhibitors. Future research directions and challenges are also discussed to facilitate the development of EZH2-targeted anticancer therapies strategies.
2026-07-17 | Management Strategies for Osseous Follicular Lymphoma of the Spine.
Primary spinal lymphoma accounts for less than 1% of spine tumors. Follicular lymphoma (FL), the most common indolent non-Hodgkin subtype, rarely involves the spine. Its indolent nature may delay diagnosis and require collaborative efforts to address diagnostic ambiguity, structural instability, and treatment. A 33-year-old male was transferred to our center with several months of progressive left leg pain and foot weakness in an L5/S1 distribution. History was notable for a sacral laminectomy four years prior for an epidural lesion diagnosed as a benign calcifying tumor with no subsequent adjuvant therapy or follow-up. Examination revealed mild left dorsiflexion and plantarflexion weakness, with intact rectal tone and sensation. Imaging demonstrated an enhancing lesion involving the L5 vertebral body with epidural extension from L5 to S1. CT-guided biopsy suggested lymphoma and was followed by surgical debulking and stabilization. Final pathology confirmed FL, and the patient received adjuvant bendamustine/rituximab with remission evidenced by resolution of pretreatment hypermetabolic foci on PET-CT with improved leg pain, strength, and absence of active disease at one-year follow-up. This case underscores the clinical and diagnostic challenges of FL. Barriers to timely adjuvant therapy heighten risks and underscore imperatives for multidisciplinary collaboration and close follow-up. Surgeons should typically advocate for biopsy or open surgery for a definitive diagnosis, stabilize fractures when necessary, and integrate oncology and radiation oncology input.
cell therapies
2026-07-30 | A distinct CAR-T cell phenotype mediates therapeutic response at limited doses.
Chimeric antigen receptor (CAR) T-cell therapies are typically administered at high doses to maximize durable clinical responses. However, manufacturing constraints can limit the production of sufficient cells to achieve the intended dose. Although some patients experience durable responses after receiving lower CAR-T cell doses, the mechanisms underlying efficacy at these limited cell numbers remain poorly understood. To address this, we performed deep phenotyping of anti-CD19 CAR-T cell products and their corresponding leukapheresis starting materials from a phase I/II dose-escalation trial. We also report the primary and secondary clinical outcomes of the diffuse large B-cell lymphoma, follicular lymphoma, and mantle cell lymphoma cohorts of the HD-CAR-1 basket trial (NCT03676504; EudraCT 2016-004808-60). Patients responding to low-dose CAR-T therapy showed dose-dependent enrichment of functional effector and effector memory-like CAR-T cells. The absolute number of these cells emerged as a robust biomarker of therapeutic response, valid across dose levels and CAR-T targets. Effective low-dose products were associated with high T-cell numbers and T-cell-supportive myeloid states in leukapheresis materials, whereas regulatory myeloid states promoted dysfunctional CAR-T cells and treatment failure. Our study provides insights into the phenotype, mechanisms, and biomarkers of CAR-T cells that drive therapeutic responses at low doses, with medical and socioeconomic implications.
2026-07-16 | Durable efficacy and manageable long-term safety of lisocabtagene maraleucel in 3L+ FL: 3-year update from TRANSCEND FL.
In the TRANSCEND FL primary analysis, lisocabtagene maraleucel (liso-cel) showed high response rates and favorable safety in patients with relapsed/refractory (R/R) follicular lymphoma (FL). Longer follow-up is needed to assess remission durability and long-term or late-onset toxicities. Here, we report 3-year follow-up results (median [range] on-study follow-up, 41.5 months [0.3‒54.0]) in patients with third-line or later (3L+) FL. Patients had R/R FL after ≥2 prior lines of combination systemic therapy, including an anti-CD20 antibody and an alkylator. A total of 107 patients received liso-cel and 103 were efficacy evaluable, with overall and complete response rates (95% CI) per independent review committee of 97% (92‒99) and 94% (88‒98), respectively. Medians were not reached for all time-to-event outcomes; estimated 36-month (95% CI) rates for duration of response, progression-free survival, time free from next treatment, and overall survival were 70% (60‒78), 68% (58‒76), 75% (70‒80), and 86% (78‒92), respectively. Response rates and 36-month time-to-event rates were consistent in high-risk subgroups, including patients with disease progression within 24 months of starting first-line immunochemotherapy, bulky disease, or double-refractory status. Longitudinal safety analyses showed decreasing grade ≥3 cytopenias and hypogammaglobulinemia (immunoglobulin G <500 mg/dL), with use of supportive care (transfusions, growth factors, intravenous immunoglobulin) mostly limited to the 3 months after infusion, and consistently low incidences of grade ≥3 infections in short- and long-term periods. At 3-year follow-up, a single liso-cel infusion delivered durable efficacy and high survival, including in high-risk subgroups, alongside a favorable long-term safety profile in patients with 3L+ FL. Clinicaltrials.gov: NCT04245839.
2026-07-16 | Long-term Remission of Severe Psoriasis Following CD19 CAR-T Cell Therapy for Follicular Lymphoma.
Psoriasis is a chronic, immune-mediated inflammatory disease in which durable, treatment-free remission is rarely achieved despite highly effective biologic therapies. We report a 60-year-old woman with a 49-year history of severe, treatment-refractory plaque psoriasis who developed complete and sustained disease clearance following autologous CD19-directed chimeric antigen receptor (CAR) T-cell therapy for follicular lymphoma. Psoriasis resolved within four weeks of CD19 CAR-T-cell therapy and has remained in remission for over 4.5 years without any psoriasis-directed treatment. This observation, together with emerging reports, suggests that deep tissue depletion of B-lymphoid lineage cells in psoriasis may induce long-term disease modification. Mechanistically, CD19 CAR-T therapy targets a broader spectrum of B-cell populations than anti-CD20 approaches, potentially disrupting pathogenic B-T cell interactions and autoreactive immune circuits. These findings challenge the prevailing T cell-centric paradigm of psoriasis and support exploration of B-cell-directed, immune reset strategies as a route towards durable remission or cure.
2026-07-05 | Efficacy and safety of CD19 CAR T-cell therapy in relapsed/refractory follicular lymphoma: A systematic review and meta-analysis.
Follicular lymphoma (FL) is an indolent B-cell non-Hodgkin lymphoma characterized by frequent relapses despite initial responsiveness to chemoimmunotherapy. CD19-directed chimeric antigen receptor (CAR) T-cell therapy has shown promising efficacy in relapsed or refractory disease, though safety concerns such as cytokine release syndrome (CRS) and neurological events remain. This study aimed to evaluate the efficacy and safety of CD19 CAR T-cell therapy in relapsed or refractory FL. A comprehensive search using six databases, including PubMed, Scopus, and Embase, was performed to identify relevant studies. Data on overall response rate (ORR), complete response rate (CRR), progression-free survival (PFS), duration of response (DOR), overall survival (OS), and adverse events, including CRS and neurological events, were extracted. Pooled estimates were calculated using the quality effects model. This review was registered in PROSPERO (CRD420251133655). Out of 2303 records initially identified, 6 studies met the inclusion criteria. The pooled efficacy analysis demonstrated an ORR of 93.5% (95% CI: 86.3-98.3%) and a CRR of 84.5% (95% CI: 72.6-93.6%). Regarding safety outcomes, the pooled estimate for CRS of any grade was 61.4% (95% CI: 45.0-76.6%). For neurological events, it was 33.6% (95% CI: 13.4-57.1%). Subgroup analyses identified prior therapy lines and CAR construct design as sources of heterogeneity. In conclusion, CD19 CAR T-cell therapy demonstrates high efficacy with a generally acceptable safety in relapsed or refractory FL, supporting its consideration for patients with limited treatment options while highlighting the need for further research on long-term outcomes.
2026-06-24 | Ten-Year Outcomes after CAR T-Cell Therapy for B-Cell Lymphomas.
Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy is a standard treatment for relapsed or refractory B-cell non-Hodgkin lymphomas. Long-term results and curative potential remain uncertain. We evaluated long-term outcomes in 38 patients with relapsed or refractory B-cell non-Hodgkin lymphomas (24 patients with large B-cell lymphoma and 14 with follicular lymphoma) who had been treated with CTL019 (now called tisagenlecleucel) - autologous T cells expressing CD19-directed, 4-1BB-costimulated chimeric receptors. Lymphoma-free survival was defined as the time from the tisagenlecleucel infusion to relapse or lymphoma-related death. The incidence of non-relapse-related death and second primary cancer was estimated with the Aalen-Johansen method. The data-cutoff date was October 1, 2025. At a median follow-up of 10.1 years (range, 7.9 to 11.5), no relapses had occurred beyond 5.4 years. The 10-year lymphoma-free survival was 32% (95% confidence interval [CI], 14 to 51) among patients with large B-cell lymphoma and 47% (95% CI, 20 to 71) among those with follicular lymphoma. In an analysis that included deaths from any cause, the 10-year progression-free survival was 17% (95% CI, 5 to 34) among patients with large B-cell lymphoma and 29% (95% CI, 9 to 52) among those with follicular lymphoma; the 10-year overall survival was 17% (95% CI, 5 to 34) and 50% (95% CI, 23 to 72), respectively. Persistent grade 2 or 3 neutropenia occurred in 2 patients (5%); no late anemia or thrombocytopenia was observed. A second primary cancer developed in 9 patients (10-year cumulative incidence, 21%). The 10-year non-relapse-related mortality was 18% (14% when deaths related to coronavirus disease 2019 were excluded). Higher CAR-transgene persistence appeared to be associated with long-term response. B-cell aplasia persisted in 44% of patients with a long-term response. Among patients with heavily pretreated B-cell non-Hodgkin lymphoma, a single infusion of tisagenlecleucel led to decade-long remissions (lymphoma-free survival) in approximately one third of the patients with large B-cell lymphomas and in nearly one half of those with follicular lymphoma. (Funded by the Richard Berman Family Innovations Center in CLL and Lymphomas and others; ClinicalTrials.gov number, NCT02030834.).
antibodies
2026-08-13 | Personalizing Maintenance Rituximab in Follicular Lymphoma: A Machine Learning Framework for Risk-Benefit Optimization.
Background: While maintenance rituximab therapy (MT) for follicular lymphoma improves progression-free survival, individual benefit varies, creating a critical need to avoid overtreatment and its associated burdens. Methods: We developed a double machine learning framework using a retrospective 404-patient cohort to estimate the individualized treatment effect of MT on the risk of disease progression within 24 months. Results: Our model revealed heterogeneity in treatment benefit, successfully distinguishing patients most likely to benefit from those who are not. A retrospective simulated application identified a "low-risk, low-benefit" subgroup that might potentially forgo MT. Furthermore, aligning historical clinical decisions with our model's recommendations was associated with a lower progression rate compared to nonalignment (14.8% vs. 38.0%). Extensive sensitivity analyses confirmed the robustness of this treatment heterogeneity against potential unmeasured confounding and temporal practice shifts. Conclusions: Supported by an updated interactive clinical decision tool, this data-driven framework provides a robust strategy to personalize MT by separating prognostic risk from predictive benefit. It serves as a hypothesis-generating template to guide future prospective risk-adapted trials and reduce unnecessary treatment in oncology.
2026-08-02 | Fixed Treatment Duration Mosunetuzumab in Patients With Relapsed or Refractory Follicular Lymphoma: Perspectives From US Advanced Practice Providers.
Mosunetuzumab is a CD20xCD3 T-cell engaging bispecific antibody that has demonstrated a manageable safety profile in patients with relapsed or refractory (R/R) non-Hodgkin lymphoma in a pivotal phase II study (GO29781; NCT02500407). Rapid identification and appropriate management of adverse events (AEs) are key for patients receiving mosunetuzumab, and advanced practice providers (APPs) play a vital role. Six APPs were surveyed, including nurse practitioners, a research nurse, clinical pharmacists, and physician assistants, from four US academic centers involved in the phase II GO29781 study of mosunetuzumab administered intravenously in patients with R/R follicular lymphoma. Advanced practice providers provided their perspectives and experiences on their roles in the education of staff and patients, and in the monitoring and management of AEs associated with mosunetuzumab treatment. APPs provided education to staff and patients around the signs and symptoms of potential AEs as well as mosunetuzumab's mechanism of action, route of administration, and dosing schedule. They were involved in monitoring patients for AEs using clinical assessments and laboratory tests and were responsible for managing AEs, ordering necessary interventions, deciding when to interrupt treatment, clearing patients for their next dose, and advising the wider medical team on steps for patient management. APPs play a key role as part of a multidisciplinary team to ensure the safety and comfort of patients receiving mosunetuzumab in the outpatient setting. The APP experiences presented here may be used to inform future clinical practice and care coordination for mosunetuzumab treatment.
2026-08-02 | Exposure-Response Analyses to Inform the Optimal Epcoritamab Monotherapy Dosing Regimen in Relapsed or Refractory Follicular Lymphoma.
Epcoritamab is approved for treating various relapsed/refractory (R/R) lymphomas. In a phase I/II study in R/R follicular lymphoma (FL) patients, epcoritamab demonstrated high response rates (EPCORE NHL-1: objective response rate [ORR]: 82.0%, complete response [CR] rate: 62.5% [N = 128]; EPCORE NHL-3: ORR: 95.2%, CR rate: 76.2% [N = 21]) with durable responses and a manageable safety profile with a 2-step step-up dosing (SUD) regimen (0.16/0.8/48 mg [full dose]; Cycles 1-3: once-weekly dosing [QW], Cycles 4-9: every 2-week dosing [Q2W], Cycles 10+: every 4-week dosing [Q4W]). A prior population pharmacokinetic model was updated and exposure-response analyses performed to support the selected dosing regimen (0.76-48 mg full doses evaluated). Higher epcoritamab exposure was associated with higher efficacy (ORR, CR rate, progression-free survival, overall survival; p < 0.05) with potential response rate plateau at 48-mg exposures. Initial response occurred in 96.2% of responders during QW with most maintaining/improving response during Q2W and Q4W, independent of Cycle 4+ exposure. No meaningful trends between epcoritamab exposure and treatment-emergent adverse events were identified, including cytokine release syndrome (CRS). Further optimization using a 3-step SUD regimen (0.16/0.8/3/48 mg), with adequate hydration and dexamethasone prophylaxis in Cycle 1, lowered CRS frequency and severity compared with the 2-step SUD regimen. Similar pharmacokinetics and B-cell depletion occurred with 3-step and 2-step SUD regimens. Median IL-6 levels remained consistently low after each Cycle-1 dose and beyond with the 3-step but not 2-step SUD regimen. These analyses support and confirm the recommended 3-step SUD regimen with 48 mg full epcoritamab dose administered QW-Q2W-Q4W in patients with R/R FL. ClinicalTrials.gov: NCT03625037, NCT04542824.
2026-07-30 | Follicular Lymphoma: Novel Therapies and Strategies for Optimal Therapeutic Sequencing.
Follicular lymphoma (FL) is the most common indolent non-Hodgkin lymphoma, characterized by a relapsing and remitting course and a median overall survival exceeding 15-20 years with modern therapy. While chemoimmunotherapy remains the cornerstone of frontline management, the rapid approval of novel agents, including bispecific antibodies, CAR T-cell products, and antibody-drug conjugates, has fundamentally reshaped the relapsed/refractory (R/R) landscape. This review summarizes current evidence across the treatment continuum and propose a practical, risk-adapted sequencing framework. Bispecific antibodies (mosunetuzumab, epcoritamab) have demonstrated durable complete responses in heavily pretreated FL, with manageable toxicity profiles. CAR T-cell therapy (axicabtagene ciloleucel, lisocabtagene maraleucel, and tisagenlecleucel) are approved in R/R FL after two or more prior lines, offering high response rates albeit notable logistal and safety considerations. Frontline trials incorporating lenalidomide-rituximab have established chemotherapy-free option with long-term outcomes comparable to chemoimmunotherapy. Emerging data on antibody-drug conjugates and bispecific antibody combination therapy continue to expand the therapeutic arsenal. Despite favorable long-term outcomes for many patients with FL, relapse remains common and remission typically shortens with successive lines of therapy. The growing number of effective agents with distinct mechanisms of action creates both opportunity and complexity. Evidence-based sequencing strategies that account for prior therapy exposure, patient fitness and mechanism-specific considerations are increasingly critical to maximizing outcomes across the disease trajectory.
2026-07-23 | Integrating Multi-Omics Mendelian Randomization and Functional Validation to Identify Novel Apoptosis Regulators in Follicular Lymphoma.
IntroductionDysregulation of apoptosis is a hallmark of follicular lymphoma (FL), yet the causal genetic drivers remain incompletely understood. This study aimed to identify causal apoptosis-related genes in FL and validate their functional roles.MethodsWe conducted a multi-omics Mendelian randomization (MR) study, integrating summary statistics from a large-scale FL genome-wide association study with data on methylation (mQTL), expression (eQTL), and protein (pQTL) quantitative trait loci. Summary data-based MR (SMR) and colocalization analyses were used to identify candidate causal genes. Independent external transcriptomic cohorts were utilized to validate the gene correlations, and evaluate the clinical prognostic relevance of the identified candidates. Key findings were then validated in FL patient tissues using RT-qPCR, and the functional role and downstream molecular mechanisms of the top candidate gene were systematically characterized through in vitro phenotypic characterization, drug sensitivity testing, and mechanistic signaling analyses.ResultsOur MR analysis identified several genes with causal links to FL risk, with integrative analysis highlighting IER3IP1, PRKCZ, and CD40. Notably, PRKCZ and CD40 exhibited significant correlation, whereas IER3IP1 displayed an independent regulatory pattern. Clinical tissue validation confirmed that IER3IP1 mRNA levels were significantly elevated in FL patient tissues. Functional studies in an FL cell line demonstrated that IER3IP1 acts as an oncogene, promoting proliferation, colony formation, and migration while inhibiting apoptosis. Mechanistically, IER3IP1 depletion promoted FOXO1-mediated transcriptional upregulation of CD20 via the XBP1/FOXO1 signaling axis, which concomitantly activated the intrinsic apoptotic pathway and significantly enhanced the sensitivity of FL cells to Rituximab-mediated cytotoxicity and apoptosis.Additionally, survival analysis revealed that CD40 serves as a strong prognostic indicator, with its low expression correlated with poorer progression-free survival and overall survival in FL patients.ConclusionsThis study provides the genetic and functional evidence establishing IER3IP1 as a novel causal oncogene in the pathogenesis of FL. Our findings elucidate the critical role of the IER3IP1-mediated XBP1/FOXO1/CD20 axis in targeted therapy resistance, highlighting IER3IP1 as a promising therapeutic target to restore apoptotic activity and improve Rituximab sensitivity.
vaccines
2024-07-29 | Neoantigen landscape supports feasibility of personalized cancer vaccine for follicular lymphoma.
Personalized cancer vaccines designed to target neoantigens represent a promising new treatment paradigm in oncology. In contrast to classical idiotype vaccines, we hypothesized that "polyvalent" vaccines could be engineered for the personalized treatment of follicular lymphoma (FL) using neoantigen discovery by combined whole-exome sequencing (WES) and RNA sequencing (RNA-seq). Fifty-eight tumor samples from 57 patients with FL underwent WES and RNA-seq. Somatic and B-cell clonotype neoantigens were predicted and filtered to identify high-quality neoantigens. B-cell clonality was determined by the alignment of B-cell receptor (BCR) CDR3 regions from RNA-seq data, grouping at the protein level, and comparison with the BCR repertoire from healthy individuals using RNA-seq data. An average of 52 somatic mutations per patient (range, 2-172) were identified, and ≥2 (median, 15) high-quality neoantigens were predicted for 56 of 58 FL samples. The predicted neoantigen peptides were composed of missense mutations (77%), indels (9%), gene fusions (3%), and BCR sequences (11%). Building off of these preclinical analyses, we initiated a pilot clinical trial using personalized neoantigen vaccination combined with PD-1 blockade in patients with relapsed or refractory FL (#NCT03121677). Synthetic long peptide vaccines targeting predicted high-quality neoantigens were successfully synthesized for and administered to all 4 patients enrolled. Initial results demonstrate feasibility, safety, and potential immunologic and clinical responses. Our study suggests that a genomics-driven personalized cancer vaccine strategy is feasible for patients with FL, and this may overcome prior challenges in the field. This trial was registered at www.ClinicalTrials.gov as #NCT03121677.
2024-07-22 | A phase I trial of vaccination with lethally irradiated lymphoma cells admixed with granulocyte-macrophage colony-stimulating factor secreting K562 cells for the treatment of follicular lymphoma.
Several vaccine strategies have been tested for the treatment of follicular lymphoma; however, none have proven successful. In a phase I dose-escalation protocol, we developed a vaccine consisting of lethally irradiated whole lymphoma cells admixed with K562 cells that constitutively secreted granulocyte-macrophage colony-stimulating factor (GM-K562)(ClinicalTrials.gov identifier: NCT00487305). Patients with grade 1, 2, or 3 A follicular lymphoma were divided into 2 study tiers based on prior treatment and received a maximum of 6 vaccines. Vaccines contained dose levels of 5 × 106 or 1 × 107 GM-K562 cells admixed with autologous tumor cells at doses ranging from 1 × 105 to 5 × 107.Correlative studies did not demonstrate a significant immune response as assessed by delayed-type hypersensitivity reactions, B and T cell subsets, and natural killer cell subsets. Future vaccine studies should focus on identifying lymphoma-specific immunogenic proteins and modifying the vaccine immune adjuvant.
2024-03-28 | Therapeutic Vaccines for Follicular Lymphoma: A Systematic Review.
(1) Background: We aimed to estimate the pooled effectiveness and safety of vaccination in follicular lymphoma (FL) and discuss implications for immunotherapy development. (2) Methods: We included randomized trials (RCTs) of therapeutic vaccines in patients with FL. Progression-free survival (PFS) was the primary outcome. We searched databases (PubMed, Embase, Scopus, Web of Science Core, medRxiv) and registries (PROSPERO, CENTRAL, ClinicalTrials.gov, EuCTR, WHO ICTRP) and conducted online, citation, and manual searches. We assessed risks of bias across outcomes using RoB 2.0 and across studies using ROB-ME and a contour-enhanced funnel plot. (3) Results: Three RCTs were included (813 patients, both previously treated and untreated). Patients with a complete or partial response after chemotherapy were randomized to either a patient-specific recombinant idiotype keyhole limpet hemocyanin (Id-KLH) vaccine plus granulocyte-macrophage colony-stimulating factor (GM-CSF) or placebo immunotherapy (KLH + GM-CSF). Meta-analyses showed that PFS was worse with the vaccine, but not significantly: hazard ratio, 1.09 (95% CI 0.91-1.30). The GRADE certainty of evidence was moderate. Adverse event data were mixed. (4) Conclusions: We are moderately certain that Id-KLH results in little to no difference in PFS in FL. (5) Funding: Russian Science Foundation grant #22-25-00516. (6) Registration: PROSPERO CRD42023457528.
2023-09-05 | Tenascin-R Autoimmunity: Isolated Tremor Reversed with Immunotherapy.
Autoimmune movement disorders are increasingly recognized, but isolated tremor is extremely rare. We describe a 70-year-old male with rapidly progressive, severe postural and intention tremor and weight loss. His cerebrospinal fluid was inflammatory and harbored a neural tissue-restricted antibody. The autoantigen was identified by immunoprecipitation and mass spectrometry and confirmed by antigen-specific assays to be specific for tenascin-R. He was investigated for cancer and diagnosed with follicular lymphoma that expressed tenascin-R suggesting a paraneoplastic origin; cancer treatment and immunotherapy led to complete recovery. With this individualized patient approach and antibody discovery, we expand the spectrum of antibodies accompanying autoimmune hyperkinetic movement disorders. ANN NEUROL 2023;94:502-507.
2022-03-07 | Rituximab-treated patients with lymphoma develop strong CD8 T-cell responses following COVID-19 vaccination.
Summary B‐cell depletion induced by anti‐cluster of differentiation 20 (CD20) monoclonal antibody (mAb) therapy of patients with lymphoma is expected to impair humoral responses to severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) vaccination, but effects on CD8 T‐cell responses are unknown. Here, we investigated humoral and CD8 T‐cell responses following two vaccinations in patients with lymphoma undergoing anti‐CD20‐mAb therapy as single agent or in combination with chemotherapy or other anti‐neoplastic agents during the last 9 months prior to inclusion, and in healthy age‐matched blood donors. Antibody measurements showed that seven of 110 patients had antibodies to the receptor‐binding domain of the SARS‐CoV‐2 Spike protein 3–6 weeks after the second dose of vaccination. Peripheral blood CD8 T‐cell responses against prevalent human leucocyte antigen (HLA) class I SARS‐CoV‐2 epitopes were determined by peptide‐HLA multimer analysis. Strong CD8 T‐cell responses were observed in samples from 20/29 patients (69%) and 12/16 (75%) controls, with similar median response magnitudes in the groups and some of the strongest responses observed in patients. We conclude that despite the absence of humoral immune responses in fully SARS‐CoV‐2‐vaccinated, anti‐CD20‐treated patients with lymphoma, their CD8 T‐cell responses reach similar frequencies and magnitudes as for controls. Patients with lymphoma on B‐cell depleting therapies are thus likely to benefit from current coronavirus disease 2019 (COVID‐19) vaccines, and development of vaccines aimed at eliciting T‐cell responses to non‐Spike epitopes might provide improved protection.
other
2025-10-16 | Proteomic Profiling of Limited-Stage Follicular Lymphoma Reveals Differentially Expressed Proteins Linked to Disease Progression Post-Radiation Therapy.
Follicular lymphoma (FL) is the most common indolent lymphoma. Despite a generally favorable prognosis and long-term survival for many patients, FL remains incurable, with disease progression occurring in approximately half of limited-stage FL cases. In this study, we employed high-throughput mass spectrometry-based proteomics to explore the differential protein expression in diagnostic lymphoma biopsies from 26 limited-stage FL patients. Of these, 9 patients experienced subsequent disease progression (sp-FL), while 17 did not (np-FL). A total of 1940 proteins were identified, with 78 showing significant differential expression between progressing and non-progressing cases. Unsupervised clustering analyses were able to separate the two patient groups based on these differential protein profiles. Notably, proteins involved in metabolism, immune regulation, and apoptosis were downregulated in sp-FL samples. Among the identified proteins, caspase 4 and 8 (CASP4 and CASP8) were further evaluated. The low expression of CASP4 in the diagnostic lymphoma tissue correlated with shorter progression-free survival (PFS) (p < 0.001), primarily with this difference apparent in the expression profiles in the intrafollicular areas (p = 0.015). Similarly, low CASP8 expression was associated with inferior PFS (p = 0.031). Interestingly, addressing the expression pattern for advanced-stage FL patients, the low protein expression of both CASP4 and CASP8 was also found to be associated with progressing cases, suggesting their potential role in disease pathogenesis independent of the disease stage. With further research, the expression pattern of CASP4 and CASP8 may enable the early prediction of disease progression in FL patients, which may ultimately improve patient stratification and allow for more individualized treatment strategies.
2025-07-11 | Galectin-9 treatment is cytotoxic for B cell lymphoma by disrupting autophagy.
The main cause of death for patients with non-Hodgkin lymphoma (NHL) remains therapy resistant relapses. Chemoresistance is commonly associated with apoptosis defects and upregulated autophagy. Therefore, novel therapeutic options that do not rely on apoptosis and target autophagy would be of interest to treat NHL. An agent that may fulfill these requirements is the glycan-binding protein Galectin-9 (Gal-9). A panel of B cell lymphoma NHL cell lines, including diffuse large B cell lymphoma (DLBCL), mantle cell lymphoma (MCL), Burkitt's lymphoma (BL), and (chemoresistant) follicular lymphoma (FL), were treated with Gal-9 after which cell counts and cell viability were determined. Basal mRNA and protein expression levels were respectively determined by RTqPCR and western blot. The impact of Gal-9 treatment on the autophagy pathway was determined using lysotracker, Cyto-ID and western blot (targeting LAMP2, p62, LC3B-I/LC3B-II). Treatment with Gal-9 reduced total cell counts and cell viability of various DLBCL, MCL, BL and FL cell lines. Gal-9-induced cell death was associated with the inhibition of autophagy, as demonstrated by the accumulation of LC3B-II and p62. In addition, Gal-9-sensitive cells expressed lower basal protein levels of LC3B-I as compared to cells that responded less to this lectin. Furthermore, Gal-9 was cytotoxic for chemoresistant Sc-1 cells (Sc-1-RES), which were even more sensitive toward Gal-9 treatment than the parental cells (Sc-1-PAR). Gal-9 is a potent inducer of B cell lymphoma cell dead by inhibiting the proper execution of autophagy.
2025-03-18 | Temporal trends in time toxicity of R-CHOP: a nationwide hospital-based database analysis in Japan.
While the prognosis of patients with cancer has improved, the time burden of treatment has recently been recognized as time toxicity; although, the actual clinical situation remains largely unexplored. This retrospective study aimed to elucidate the time toxicity of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in patients with B-cell lymphoma and the factors influencing it. We used a nationwide hospital-based database between January 2010 and November 2021 in Japan. We extracted the claims data of patients with diffuse large B-cell lymphoma and follicular lymphoma who were hospitalized and/or visited hospitals for chemotherapy. Among the 7760 R-CHOP administered to 2006 patients, the rate of outpatient therapy increased over time (2010-2015: 17.9%; 2016-2021: 31.8%). In 2016, the median length of hospitalization was the shortest at 13 days (IQR 8-19), which coincided with the peak use of pegylated granulocyte colony-stimulating factor (Peg-G-CSF) during hospitalization in 2015-2016, likely driven by changes in the insurance system. In multivariate analysis, the factors associated with longer hospital stays were older age and poor activities of daily living, whereas the use of Peg-G-CSF, a reduced-dose regimen, and treatment at cancer-designated hospitals were associated with shorter stays. The time toxicity of R-CHOP has improved and may be influenced by the patient's condition, adequate supportive care, changes in the insurance system, and center-specific treatment proficiency.
2024-09-08 | Hypogammaglobulinemia and Anti-CD20 Therapy-Induced Acute Thrombocytopenia: Perhaps More than a Coincidence?
The development of secondary hypogammaglobulinemia (sHGG) because of tumor treatment and/or the primary underlying hematologic disorder holds substantial clinical significance. B-cell-derived malignancies and anti-CD20 monoclonal antibodies (mAbs) represent important risk factors for the development of sHGG. In addition, the occurrence of acute thrombocytopenia (AT) induced by anti-CD20 therapy is a known, albeit rare, phenomenon. A 54-year-old patient experiencing the first relapse of classical follicular lymphoma has commenced salvage therapy following the R-DHAP protocol. After rituximab infusion, platelet count dropped from 116 × 109/L to 13 × 109/L within 24 h. Reduced immunoglobulin G levels indicated moderate HGG; thus, we immediately administered intravenous immunoglobulins (IVIg). Within 5 days after initiation of IVIg, platelet count increased and stabilized at >50 × 109/L. It seems possible that anti-CD20 mAbs act like or activate similar mechanisms as autoantibodies in immune thrombocytopenia (ITP). Assuming that anti-CD20 therapy-induced AT is an ITP-like condition, HGG could be considered a potential risk factor. Thus, appropriate treatment of HGG with IVIg prior to anti-CD20 mAb therapy could potentially alleviate anti-CD20 therapy-induced AT.
2024-09-04 | Efficacy and Safety of Bendamustine-Rituximab as Frontline Therapy for Indolent Non-Hodgkin Lymphoma: A Real-World, Single-Center, Retrospective Study.
Background The use of bendamustine with an anti-CD20 monoclonal antibody as frontline therapy for indolent non-Hodgkin lymphoma (NHL) has become a standard of care. We aimed to evaluate the real-world efficacy and safety of bendamustine-rituximab (BR) frontline therapy for indolent NHL. Patients and methods Patients with indolent NHL treated with frontline BR therapy in Hôpital du Sacré-Coeur de Montréal, from January 2015 to August 2018 were included in this retrospective study. Results Our cohort included 42 adults with a median age of 63 years. Follicular lymphoma was the most common histology (n = 31, 74%). Most patients had advanced disease (Lugano stage III or IV, 88%). The overall response rate was 84% (complete response = 62% and partial response = 22%). Median progression-free survival (PFS) was not reached. At 30 months, PFS was 74.8% and overall survival was 90%. Grade 3-4 neutropenia occurred in 21% of patients. Infection-related adverse events were observed in 17 patients (40%). Most were grade 1 and 2 events (84%). One case of grade 5 progressive multifocal leukoencephalopathy related to John Cunningham (JC) virus reactivation was observed. The most common non-infectious-related adverse events were mild nausea and fatigue. Conclusions The efficacy and safety of BR treatment for indolent NHL were comparable in our real-life cohort compared to prior studies. This supports BR as a standard of care for indolent NHL. Future studies should assess whether the use of granulocyte-colony stimulating factors as primary prophylaxis effectively mitigates the hematological and infection-related adverse events related to BR therapy.
small molecules
2026-08-13 | Follicular Lymphoma Arising in an Ileal Neobladder Presenting as a Large Pelvic Mass.
Secondary malignancies arising in intestinal segments used for urinary diversion are rare, and reports of malignant lymphoma are extremely limited. We report a rare case of follicular lymphoma arising in an ileal neobladder 20 years after radical cystectomy. An 81-year-old man had undergone radical cystectomy with ileal neobladder reconstruction for muscle-invasive bladder cancer (pT2bN0M0) 20 years earlier and had remained recurrence-free. Follow-up imaging incidentally revealed a large pelvic mass contiguous with the neobladder and multiple enlarged lymph nodes. Transurethral resection led to a diagnosis of follicular lymphoma. Treatment with bendamustine plus rituximab achieved marked tumor reduction without severe adverse events. Malignant lymphoma arising in urinary diversion organs is extremely rare. This case highlights the potential for late-onset lymphoid malignancies following urinary diversion and emphasizes the need for long-term clinical awareness of secondary malignancies in such patients.
2026-07-28 | A Multi-Targeted Strategy for Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma: Real-World Outcomes of the ViPOR Regimen.
Background/Objectives: Relapsed/refractory (R/R) B-cell non-Hodgkin lymphomas (B-NHLs) remain a major therapeutic challenge, particularly in patients with aggressive subtypes and limited treatment options after multiple lines of therapy. The ViPOR regimen, a multi-targeted combination of venetoclax, ibrutinib, prednisone, obinutuzumab, and lenalidomide, has demonstrated promising activity in early-phase studies; however, real-world data are limited. Methods: We conducted a retrospective, two-center study including patients with R/R B-NHL treated with the ViPOR regimen between January 2024 and April 2026. Clinical characteristics, treatment responses, survival outcomes, and safety data were analyzed. Results: A total of 14 patients were included, with a median age of 45 years and a median of 3.5 prior lines of therapy. Most patients had advanced-stage disease (71% stage IV), and 36% had primary refractory disease. The interim overall response rate (ORR) was 62%, including 31% complete response (CR) and 31% partial response. At the end of treatment, the ORR was 54%, with a CR rate of 54%. Radiotherapy was incorporated in selected patients with residual disease and contributed to response deepening. Six patients (43%) were successfully bridged to allogeneic stem cell transplantation, all in CR. Responses were notably more favorable in the activated B-cell (ABC) subtype compared to the germinal center subtype. The most common adverse events were neutropenia (57%) and diarrhea (36%), and the regimen demonstrated a manageable safety profile. During follow-up, 57% of patients remained alive. Conclusions: The ViPOR regimen demonstrated promising efficacy and acceptable safety in heavily pretreated R/R B-NHL, particularly in the ABC subtype. Its ability to induce deep responses and enable bridging to allogeneic stem cell transplantation highlights its potential role in real-world clinical practice. Larger prospective studies are warranted to confirm these findings.
2026-07-26 | Covalent Bruton's tyrosine kinase inhibitor HZ-A-018 in patients with relapsed or refractory B cell malignancies: A multicenter phase I study.
HZ-A-018 represents a highly selective, covalent, novel inhibitor targeting Bruton's tyrosine kinase (BTK). This multicenter, open-label phase I study enrolled 32 patients with relapsed/refractory B cell malignancies (including diffuse large B cell lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma, Waldenström macroglobulinemia, follicular lymphoma, mantle cell lymphoma, and marginal zone lymphoma) in dose-escalation and -expansion phases. Thirty-one patients received treatment: 15 in the dose-escalation phase (75-550 mg once daily) and 16 in the expansion phase (300 mg once daily). No dose-limiting toxicities or maximum tolerated dose were identified. The most common treatment-emergent adverse events included cytopenias, rash, and hypertension. Among 29 efficacy-evaluable patients, with a median follow-up of 4.9 months, the overall response rate was 44.8%. Pharmacokinetics revealed dose-proportional exposure, and median BTK occupancy in peripheral blood mononuclear cells surpassed 95% across all dose levels at steady state. HZ-A-018 demonstrated acceptable safety and antitumor activity, supporting further clinical development.
2026-07-23 | Epigenetic and Non-Epigenetic Functions of EZH2 in Tumor Development: Structural Basis, Signaling Network, and Targeted Intervention Strategies.
Enhancer of Zeste Homolog 2 (EZH2) is a histone methyltransferase that catalyzes the methylation of histone H3 lysine 27, a modification frequently dysregulated in various cancers. EZH2 plays critical roles in cell proliferation, differentiation, and gene silencing, and its abnormal overexpression is closely associated with tumor aggressiveness and poor prognosis. Inhibiting EZH2 can reactivate tumor suppressor genes and thereby suppress cancer cell growth and metastasis. Although several EZH2 inhibitors, including small molecules and nucleic acid drugs, have been developed and some have entered clinical trials, their specificity and potency still require further optimization. Tazemetostat is the first FDA-approved EZH2 inhibitor for relapsed or refractory follicular lymphoma, while other agents such as EPZ-6438 and GSK126 show promising preclinical antitumor activity. This review summarizes the association between EZH2 and tumors, and the mechanisms and pharmacological properties of EZH2 inhibitors. Future research directions and challenges are also discussed to facilitate the development of EZH2-targeted anticancer therapies strategies.
2026-07-17 | Management Strategies for Osseous Follicular Lymphoma of the Spine.
Primary spinal lymphoma accounts for less than 1% of spine tumors. Follicular lymphoma (FL), the most common indolent non-Hodgkin subtype, rarely involves the spine. Its indolent nature may delay diagnosis and require collaborative efforts to address diagnostic ambiguity, structural instability, and treatment. A 33-year-old male was transferred to our center with several months of progressive left leg pain and foot weakness in an L5/S1 distribution. History was notable for a sacral laminectomy four years prior for an epidural lesion diagnosed as a benign calcifying tumor with no subsequent adjuvant therapy or follow-up. Examination revealed mild left dorsiflexion and plantarflexion weakness, with intact rectal tone and sensation. Imaging demonstrated an enhancing lesion involving the L5 vertebral body with epidural extension from L5 to S1. CT-guided biopsy suggested lymphoma and was followed by surgical debulking and stabilization. Final pathology confirmed FL, and the patient received adjuvant bendamustine/rituximab with remission evidenced by resolution of pretreatment hypermetabolic foci on PET-CT with improved leg pain, strength, and absence of active disease at one-year follow-up. This case underscores the clinical and diagnostic challenges of FL. Barriers to timely adjuvant therapy heighten risks and underscore imperatives for multidisciplinary collaboration and close follow-up. Surgeons should typically advocate for biopsy or open surgery for a definitive diagnosis, stabilize fractures when necessary, and integrate oncology and radiation oncology input.
cell therapies
2026-07-30 | A distinct CAR-T cell phenotype mediates therapeutic response at limited doses.
Chimeric antigen receptor (CAR) T-cell therapies are typically administered at high doses to maximize durable clinical responses. However, manufacturing constraints can limit the production of sufficient cells to achieve the intended dose. Although some patients experience durable responses after receiving lower CAR-T cell doses, the mechanisms underlying efficacy at these limited cell numbers remain poorly understood. To address this, we performed deep phenotyping of anti-CD19 CAR-T cell products and their corresponding leukapheresis starting materials from a phase I/II dose-escalation trial. We also report the primary and secondary clinical outcomes of the diffuse large B-cell lymphoma, follicular lymphoma, and mantle cell lymphoma cohorts of the HD-CAR-1 basket trial (NCT03676504; EudraCT 2016-004808-60). Patients responding to low-dose CAR-T therapy showed dose-dependent enrichment of functional effector and effector memory-like CAR-T cells. The absolute number of these cells emerged as a robust biomarker of therapeutic response, valid across dose levels and CAR-T targets. Effective low-dose products were associated with high T-cell numbers and T-cell-supportive myeloid states in leukapheresis materials, whereas regulatory myeloid states promoted dysfunctional CAR-T cells and treatment failure. Our study provides insights into the phenotype, mechanisms, and biomarkers of CAR-T cells that drive therapeutic responses at low doses, with medical and socioeconomic implications.
2026-07-16 | Durable efficacy and manageable long-term safety of lisocabtagene maraleucel in 3L+ FL: 3-year update from TRANSCEND FL.
In the TRANSCEND FL primary analysis, lisocabtagene maraleucel (liso-cel) showed high response rates and favorable safety in patients with relapsed/refractory (R/R) follicular lymphoma (FL). Longer follow-up is needed to assess remission durability and long-term or late-onset toxicities. Here, we report 3-year follow-up results (median [range] on-study follow-up, 41.5 months [0.3‒54.0]) in patients with third-line or later (3L+) FL. Patients had R/R FL after ≥2 prior lines of combination systemic therapy, including an anti-CD20 antibody and an alkylator. A total of 107 patients received liso-cel and 103 were efficacy evaluable, with overall and complete response rates (95% CI) per independent review committee of 97% (92‒99) and 94% (88‒98), respectively. Medians were not reached for all time-to-event outcomes; estimated 36-month (95% CI) rates for duration of response, progression-free survival, time free from next treatment, and overall survival were 70% (60‒78), 68% (58‒76), 75% (70‒80), and 86% (78‒92), respectively. Response rates and 36-month time-to-event rates were consistent in high-risk subgroups, including patients with disease progression within 24 months of starting first-line immunochemotherapy, bulky disease, or double-refractory status. Longitudinal safety analyses showed decreasing grade ≥3 cytopenias and hypogammaglobulinemia (immunoglobulin G <500 mg/dL), with use of supportive care (transfusions, growth factors, intravenous immunoglobulin) mostly limited to the 3 months after infusion, and consistently low incidences of grade ≥3 infections in short- and long-term periods. At 3-year follow-up, a single liso-cel infusion delivered durable efficacy and high survival, including in high-risk subgroups, alongside a favorable long-term safety profile in patients with 3L+ FL. Clinicaltrials.gov: NCT04245839.
2026-07-16 | Long-term Remission of Severe Psoriasis Following CD19 CAR-T Cell Therapy for Follicular Lymphoma.
Psoriasis is a chronic, immune-mediated inflammatory disease in which durable, treatment-free remission is rarely achieved despite highly effective biologic therapies. We report a 60-year-old woman with a 49-year history of severe, treatment-refractory plaque psoriasis who developed complete and sustained disease clearance following autologous CD19-directed chimeric antigen receptor (CAR) T-cell therapy for follicular lymphoma. Psoriasis resolved within four weeks of CD19 CAR-T-cell therapy and has remained in remission for over 4.5 years without any psoriasis-directed treatment. This observation, together with emerging reports, suggests that deep tissue depletion of B-lymphoid lineage cells in psoriasis may induce long-term disease modification. Mechanistically, CD19 CAR-T therapy targets a broader spectrum of B-cell populations than anti-CD20 approaches, potentially disrupting pathogenic B-T cell interactions and autoreactive immune circuits. These findings challenge the prevailing T cell-centric paradigm of psoriasis and support exploration of B-cell-directed, immune reset strategies as a route towards durable remission or cure.
2026-07-05 | Efficacy and safety of CD19 CAR T-cell therapy in relapsed/refractory follicular lymphoma: A systematic review and meta-analysis.
Follicular lymphoma (FL) is an indolent B-cell non-Hodgkin lymphoma characterized by frequent relapses despite initial responsiveness to chemoimmunotherapy. CD19-directed chimeric antigen receptor (CAR) T-cell therapy has shown promising efficacy in relapsed or refractory disease, though safety concerns such as cytokine release syndrome (CRS) and neurological events remain. This study aimed to evaluate the efficacy and safety of CD19 CAR T-cell therapy in relapsed or refractory FL. A comprehensive search using six databases, including PubMed, Scopus, and Embase, was performed to identify relevant studies. Data on overall response rate (ORR), complete response rate (CRR), progression-free survival (PFS), duration of response (DOR), overall survival (OS), and adverse events, including CRS and neurological events, were extracted. Pooled estimates were calculated using the quality effects model. This review was registered in PROSPERO (CRD420251133655). Out of 2303 records initially identified, 6 studies met the inclusion criteria. The pooled efficacy analysis demonstrated an ORR of 93.5% (95% CI: 86.3-98.3%) and a CRR of 84.5% (95% CI: 72.6-93.6%). Regarding safety outcomes, the pooled estimate for CRS of any grade was 61.4% (95% CI: 45.0-76.6%). For neurological events, it was 33.6% (95% CI: 13.4-57.1%). Subgroup analyses identified prior therapy lines and CAR construct design as sources of heterogeneity. In conclusion, CD19 CAR T-cell therapy demonstrates high efficacy with a generally acceptable safety in relapsed or refractory FL, supporting its consideration for patients with limited treatment options while highlighting the need for further research on long-term outcomes.
2026-06-24 | Ten-Year Outcomes after CAR T-Cell Therapy for B-Cell Lymphomas.
Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy is a standard treatment for relapsed or refractory B-cell non-Hodgkin lymphomas. Long-term results and curative potential remain uncertain. We evaluated long-term outcomes in 38 patients with relapsed or refractory B-cell non-Hodgkin lymphomas (24 patients with large B-cell lymphoma and 14 with follicular lymphoma) who had been treated with CTL019 (now called tisagenlecleucel) - autologous T cells expressing CD19-directed, 4-1BB-costimulated chimeric receptors. Lymphoma-free survival was defined as the time from the tisagenlecleucel infusion to relapse or lymphoma-related death. The incidence of non-relapse-related death and second primary cancer was estimated with the Aalen-Johansen method. The data-cutoff date was October 1, 2025. At a median follow-up of 10.1 years (range, 7.9 to 11.5), no relapses had occurred beyond 5.4 years. The 10-year lymphoma-free survival was 32% (95% confidence interval [CI], 14 to 51) among patients with large B-cell lymphoma and 47% (95% CI, 20 to 71) among those with follicular lymphoma. In an analysis that included deaths from any cause, the 10-year progression-free survival was 17% (95% CI, 5 to 34) among patients with large B-cell lymphoma and 29% (95% CI, 9 to 52) among those with follicular lymphoma; the 10-year overall survival was 17% (95% CI, 5 to 34) and 50% (95% CI, 23 to 72), respectively. Persistent grade 2 or 3 neutropenia occurred in 2 patients (5%); no late anemia or thrombocytopenia was observed. A second primary cancer developed in 9 patients (10-year cumulative incidence, 21%). The 10-year non-relapse-related mortality was 18% (14% when deaths related to coronavirus disease 2019 were excluded). Higher CAR-transgene persistence appeared to be associated with long-term response. B-cell aplasia persisted in 44% of patients with a long-term response. Among patients with heavily pretreated B-cell non-Hodgkin lymphoma, a single infusion of tisagenlecleucel led to decade-long remissions (lymphoma-free survival) in approximately one third of the patients with large B-cell lymphomas and in nearly one half of those with follicular lymphoma. (Funded by the Richard Berman Family Innovations Center in CLL and Lymphomas and others; ClinicalTrials.gov number, NCT02030834.).
antibodies
2026-08-13 | Personalizing Maintenance Rituximab in Follicular Lymphoma: A Machine Learning Framework for Risk-Benefit Optimization.
Background: While maintenance rituximab therapy (MT) for follicular lymphoma improves progression-free survival, individual benefit varies, creating a critical need to avoid overtreatment and its associated burdens. Methods: We developed a double machine learning framework using a retrospective 404-patient cohort to estimate the individualized treatment effect of MT on the risk of disease progression within 24 months. Results: Our model revealed heterogeneity in treatment benefit, successfully distinguishing patients most likely to benefit from those who are not. A retrospective simulated application identified a "low-risk, low-benefit" subgroup that might potentially forgo MT. Furthermore, aligning historical clinical decisions with our model's recommendations was associated with a lower progression rate compared to nonalignment (14.8% vs. 38.0%). Extensive sensitivity analyses confirmed the robustness of this treatment heterogeneity against potential unmeasured confounding and temporal practice shifts. Conclusions: Supported by an updated interactive clinical decision tool, this data-driven framework provides a robust strategy to personalize MT by separating prognostic risk from predictive benefit. It serves as a hypothesis-generating template to guide future prospective risk-adapted trials and reduce unnecessary treatment in oncology.
2026-08-02 | Fixed Treatment Duration Mosunetuzumab in Patients With Relapsed or Refractory Follicular Lymphoma: Perspectives From US Advanced Practice Providers.
Mosunetuzumab is a CD20xCD3 T-cell engaging bispecific antibody that has demonstrated a manageable safety profile in patients with relapsed or refractory (R/R) non-Hodgkin lymphoma in a pivotal phase II study (GO29781; NCT02500407). Rapid identification and appropriate management of adverse events (AEs) are key for patients receiving mosunetuzumab, and advanced practice providers (APPs) play a vital role. Six APPs were surveyed, including nurse practitioners, a research nurse, clinical pharmacists, and physician assistants, from four US academic centers involved in the phase II GO29781 study of mosunetuzumab administered intravenously in patients with R/R follicular lymphoma. Advanced practice providers provided their perspectives and experiences on their roles in the education of staff and patients, and in the monitoring and management of AEs associated with mosunetuzumab treatment. APPs provided education to staff and patients around the signs and symptoms of potential AEs as well as mosunetuzumab's mechanism of action, route of administration, and dosing schedule. They were involved in monitoring patients for AEs using clinical assessments and laboratory tests and were responsible for managing AEs, ordering necessary interventions, deciding when to interrupt treatment, clearing patients for their next dose, and advising the wider medical team on steps for patient management. APPs play a key role as part of a multidisciplinary team to ensure the safety and comfort of patients receiving mosunetuzumab in the outpatient setting. The APP experiences presented here may be used to inform future clinical practice and care coordination for mosunetuzumab treatment.
2026-08-02 | Exposure-Response Analyses to Inform the Optimal Epcoritamab Monotherapy Dosing Regimen in Relapsed or Refractory Follicular Lymphoma.
Epcoritamab is approved for treating various relapsed/refractory (R/R) lymphomas. In a phase I/II study in R/R follicular lymphoma (FL) patients, epcoritamab demonstrated high response rates (EPCORE NHL-1: objective response rate [ORR]: 82.0%, complete response [CR] rate: 62.5% [N = 128]; EPCORE NHL-3: ORR: 95.2%, CR rate: 76.2% [N = 21]) with durable responses and a manageable safety profile with a 2-step step-up dosing (SUD) regimen (0.16/0.8/48 mg [full dose]; Cycles 1-3: once-weekly dosing [QW], Cycles 4-9: every 2-week dosing [Q2W], Cycles 10+: every 4-week dosing [Q4W]). A prior population pharmacokinetic model was updated and exposure-response analyses performed to support the selected dosing regimen (0.76-48 mg full doses evaluated). Higher epcoritamab exposure was associated with higher efficacy (ORR, CR rate, progression-free survival, overall survival; p < 0.05) with potential response rate plateau at 48-mg exposures. Initial response occurred in 96.2% of responders during QW with most maintaining/improving response during Q2W and Q4W, independent of Cycle 4+ exposure. No meaningful trends between epcoritamab exposure and treatment-emergent adverse events were identified, including cytokine release syndrome (CRS). Further optimization using a 3-step SUD regimen (0.16/0.8/3/48 mg), with adequate hydration and dexamethasone prophylaxis in Cycle 1, lowered CRS frequency and severity compared with the 2-step SUD regimen. Similar pharmacokinetics and B-cell depletion occurred with 3-step and 2-step SUD regimens. Median IL-6 levels remained consistently low after each Cycle-1 dose and beyond with the 3-step but not 2-step SUD regimen. These analyses support and confirm the recommended 3-step SUD regimen with 48 mg full epcoritamab dose administered QW-Q2W-Q4W in patients with R/R FL. ClinicalTrials.gov: NCT03625037, NCT04542824.
2026-07-30 | Follicular Lymphoma: Novel Therapies and Strategies for Optimal Therapeutic Sequencing.
Follicular lymphoma (FL) is the most common indolent non-Hodgkin lymphoma, characterized by a relapsing and remitting course and a median overall survival exceeding 15-20 years with modern therapy. While chemoimmunotherapy remains the cornerstone of frontline management, the rapid approval of novel agents, including bispecific antibodies, CAR T-cell products, and antibody-drug conjugates, has fundamentally reshaped the relapsed/refractory (R/R) landscape. This review summarizes current evidence across the treatment continuum and propose a practical, risk-adapted sequencing framework. Bispecific antibodies (mosunetuzumab, epcoritamab) have demonstrated durable complete responses in heavily pretreated FL, with manageable toxicity profiles. CAR T-cell therapy (axicabtagene ciloleucel, lisocabtagene maraleucel, and tisagenlecleucel) are approved in R/R FL after two or more prior lines, offering high response rates albeit notable logistal and safety considerations. Frontline trials incorporating lenalidomide-rituximab have established chemotherapy-free option with long-term outcomes comparable to chemoimmunotherapy. Emerging data on antibody-drug conjugates and bispecific antibody combination therapy continue to expand the therapeutic arsenal. Despite favorable long-term outcomes for many patients with FL, relapse remains common and remission typically shortens with successive lines of therapy. The growing number of effective agents with distinct mechanisms of action creates both opportunity and complexity. Evidence-based sequencing strategies that account for prior therapy exposure, patient fitness and mechanism-specific considerations are increasingly critical to maximizing outcomes across the disease trajectory.
2026-07-23 | Integrating Multi-Omics Mendelian Randomization and Functional Validation to Identify Novel Apoptosis Regulators in Follicular Lymphoma.
IntroductionDysregulation of apoptosis is a hallmark of follicular lymphoma (FL), yet the causal genetic drivers remain incompletely understood. This study aimed to identify causal apoptosis-related genes in FL and validate their functional roles.MethodsWe conducted a multi-omics Mendelian randomization (MR) study, integrating summary statistics from a large-scale FL genome-wide association study with data on methylation (mQTL), expression (eQTL), and protein (pQTL) quantitative trait loci. Summary data-based MR (SMR) and colocalization analyses were used to identify candidate causal genes. Independent external transcriptomic cohorts were utilized to validate the gene correlations, and evaluate the clinical prognostic relevance of the identified candidates. Key findings were then validated in FL patient tissues using RT-qPCR, and the functional role and downstream molecular mechanisms of the top candidate gene were systematically characterized through in vitro phenotypic characterization, drug sensitivity testing, and mechanistic signaling analyses.ResultsOur MR analysis identified several genes with causal links to FL risk, with integrative analysis highlighting IER3IP1, PRKCZ, and CD40. Notably, PRKCZ and CD40 exhibited significant correlation, whereas IER3IP1 displayed an independent regulatory pattern. Clinical tissue validation confirmed that IER3IP1 mRNA levels were significantly elevated in FL patient tissues. Functional studies in an FL cell line demonstrated that IER3IP1 acts as an oncogene, promoting proliferation, colony formation, and migration while inhibiting apoptosis. Mechanistically, IER3IP1 depletion promoted FOXO1-mediated transcriptional upregulation of CD20 via the XBP1/FOXO1 signaling axis, which concomitantly activated the intrinsic apoptotic pathway and significantly enhanced the sensitivity of FL cells to Rituximab-mediated cytotoxicity and apoptosis.Additionally, survival analysis revealed that CD40 serves as a strong prognostic indicator, with its low expression correlated with poorer progression-free survival and overall survival in FL patients.ConclusionsThis study provides the genetic and functional evidence establishing IER3IP1 as a novel causal oncogene in the pathogenesis of FL. Our findings elucidate the critical role of the IER3IP1-mediated XBP1/FOXO1/CD20 axis in targeted therapy resistance, highlighting IER3IP1 as a promising therapeutic target to restore apoptotic activity and improve Rituximab sensitivity.
vaccines
2024-07-29 | Neoantigen landscape supports feasibility of personalized cancer vaccine for follicular lymphoma.
Personalized cancer vaccines designed to target neoantigens represent a promising new treatment paradigm in oncology. In contrast to classical idiotype vaccines, we hypothesized that "polyvalent" vaccines could be engineered for the personalized treatment of follicular lymphoma (FL) using neoantigen discovery by combined whole-exome sequencing (WES) and RNA sequencing (RNA-seq). Fifty-eight tumor samples from 57 patients with FL underwent WES and RNA-seq. Somatic and B-cell clonotype neoantigens were predicted and filtered to identify high-quality neoantigens. B-cell clonality was determined by the alignment of B-cell receptor (BCR) CDR3 regions from RNA-seq data, grouping at the protein level, and comparison with the BCR repertoire from healthy individuals using RNA-seq data. An average of 52 somatic mutations per patient (range, 2-172) were identified, and ≥2 (median, 15) high-quality neoantigens were predicted for 56 of 58 FL samples. The predicted neoantigen peptides were composed of missense mutations (77%), indels (9%), gene fusions (3%), and BCR sequences (11%). Building off of these preclinical analyses, we initiated a pilot clinical trial using personalized neoantigen vaccination combined with PD-1 blockade in patients with relapsed or refractory FL (#NCT03121677). Synthetic long peptide vaccines targeting predicted high-quality neoantigens were successfully synthesized for and administered to all 4 patients enrolled. Initial results demonstrate feasibility, safety, and potential immunologic and clinical responses. Our study suggests that a genomics-driven personalized cancer vaccine strategy is feasible for patients with FL, and this may overcome prior challenges in the field. This trial was registered at www.ClinicalTrials.gov as #NCT03121677.
2024-07-22 | A phase I trial of vaccination with lethally irradiated lymphoma cells admixed with granulocyte-macrophage colony-stimulating factor secreting K562 cells for the treatment of follicular lymphoma.
Several vaccine strategies have been tested for the treatment of follicular lymphoma; however, none have proven successful. In a phase I dose-escalation protocol, we developed a vaccine consisting of lethally irradiated whole lymphoma cells admixed with K562 cells that constitutively secreted granulocyte-macrophage colony-stimulating factor (GM-K562)(ClinicalTrials.gov identifier: NCT00487305). Patients with grade 1, 2, or 3 A follicular lymphoma were divided into 2 study tiers based on prior treatment and received a maximum of 6 vaccines. Vaccines contained dose levels of 5 × 106 or 1 × 107 GM-K562 cells admixed with autologous tumor cells at doses ranging from 1 × 105 to 5 × 107.Correlative studies did not demonstrate a significant immune response as assessed by delayed-type hypersensitivity reactions, B and T cell subsets, and natural killer cell subsets. Future vaccine studies should focus on identifying lymphoma-specific immunogenic proteins and modifying the vaccine immune adjuvant.
2024-03-28 | Therapeutic Vaccines for Follicular Lymphoma: A Systematic Review.
(1) Background: We aimed to estimate the pooled effectiveness and safety of vaccination in follicular lymphoma (FL) and discuss implications for immunotherapy development. (2) Methods: We included randomized trials (RCTs) of therapeutic vaccines in patients with FL. Progression-free survival (PFS) was the primary outcome. We searched databases (PubMed, Embase, Scopus, Web of Science Core, medRxiv) and registries (PROSPERO, CENTRAL, ClinicalTrials.gov, EuCTR, WHO ICTRP) and conducted online, citation, and manual searches. We assessed risks of bias across outcomes using RoB 2.0 and across studies using ROB-ME and a contour-enhanced funnel plot. (3) Results: Three RCTs were included (813 patients, both previously treated and untreated). Patients with a complete or partial response after chemotherapy were randomized to either a patient-specific recombinant idiotype keyhole limpet hemocyanin (Id-KLH) vaccine plus granulocyte-macrophage colony-stimulating factor (GM-CSF) or placebo immunotherapy (KLH + GM-CSF). Meta-analyses showed that PFS was worse with the vaccine, but not significantly: hazard ratio, 1.09 (95% CI 0.91-1.30). The GRADE certainty of evidence was moderate. Adverse event data were mixed. (4) Conclusions: We are moderately certain that Id-KLH results in little to no difference in PFS in FL. (5) Funding: Russian Science Foundation grant #22-25-00516. (6) Registration: PROSPERO CRD42023457528.
2023-09-05 | Tenascin-R Autoimmunity: Isolated Tremor Reversed with Immunotherapy.
Autoimmune movement disorders are increasingly recognized, but isolated tremor is extremely rare. We describe a 70-year-old male with rapidly progressive, severe postural and intention tremor and weight loss. His cerebrospinal fluid was inflammatory and harbored a neural tissue-restricted antibody. The autoantigen was identified by immunoprecipitation and mass spectrometry and confirmed by antigen-specific assays to be specific for tenascin-R. He was investigated for cancer and diagnosed with follicular lymphoma that expressed tenascin-R suggesting a paraneoplastic origin; cancer treatment and immunotherapy led to complete recovery. With this individualized patient approach and antibody discovery, we expand the spectrum of antibodies accompanying autoimmune hyperkinetic movement disorders. ANN NEUROL 2023;94:502-507.
2022-03-07 | Rituximab-treated patients with lymphoma develop strong CD8 T-cell responses following COVID-19 vaccination.
Summary B‐cell depletion induced by anti‐cluster of differentiation 20 (CD20) monoclonal antibody (mAb) therapy of patients with lymphoma is expected to impair humoral responses to severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) vaccination, but effects on CD8 T‐cell responses are unknown. Here, we investigated humoral and CD8 T‐cell responses following two vaccinations in patients with lymphoma undergoing anti‐CD20‐mAb therapy as single agent or in combination with chemotherapy or other anti‐neoplastic agents during the last 9 months prior to inclusion, and in healthy age‐matched blood donors. Antibody measurements showed that seven of 110 patients had antibodies to the receptor‐binding domain of the SARS‐CoV‐2 Spike protein 3–6 weeks after the second dose of vaccination. Peripheral blood CD8 T‐cell responses against prevalent human leucocyte antigen (HLA) class I SARS‐CoV‐2 epitopes were determined by peptide‐HLA multimer analysis. Strong CD8 T‐cell responses were observed in samples from 20/29 patients (69%) and 12/16 (75%) controls, with similar median response magnitudes in the groups and some of the strongest responses observed in patients. We conclude that despite the absence of humoral immune responses in fully SARS‐CoV‐2‐vaccinated, anti‐CD20‐treated patients with lymphoma, their CD8 T‐cell responses reach similar frequencies and magnitudes as for controls. Patients with lymphoma on B‐cell depleting therapies are thus likely to benefit from current coronavirus disease 2019 (COVID‐19) vaccines, and development of vaccines aimed at eliciting T‐cell responses to non‐Spike epitopes might provide improved protection.
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2025-10-16 | Proteomic Profiling of Limited-Stage Follicular Lymphoma Reveals Differentially Expressed Proteins Linked to Disease Progression Post-Radiation Therapy.
Follicular lymphoma (FL) is the most common indolent lymphoma. Despite a generally favorable prognosis and long-term survival for many patients, FL remains incurable, with disease progression occurring in approximately half of limited-stage FL cases. In this study, we employed high-throughput mass spectrometry-based proteomics to explore the differential protein expression in diagnostic lymphoma biopsies from 26 limited-stage FL patients. Of these, 9 patients experienced subsequent disease progression (sp-FL), while 17 did not (np-FL). A total of 1940 proteins were identified, with 78 showing significant differential expression between progressing and non-progressing cases. Unsupervised clustering analyses were able to separate the two patient groups based on these differential protein profiles. Notably, proteins involved in metabolism, immune regulation, and apoptosis were downregulated in sp-FL samples. Among the identified proteins, caspase 4 and 8 (CASP4 and CASP8) were further evaluated. The low expression of CASP4 in the diagnostic lymphoma tissue correlated with shorter progression-free survival (PFS) (p < 0.001), primarily with this difference apparent in the expression profiles in the intrafollicular areas (p = 0.015). Similarly, low CASP8 expression was associated with inferior PFS (p = 0.031). Interestingly, addressing the expression pattern for advanced-stage FL patients, the low protein expression of both CASP4 and CASP8 was also found to be associated with progressing cases, suggesting their potential role in disease pathogenesis independent of the disease stage. With further research, the expression pattern of CASP4 and CASP8 may enable the early prediction of disease progression in FL patients, which may ultimately improve patient stratification and allow for more individualized treatment strategies.
2025-07-11 | Galectin-9 treatment is cytotoxic for B cell lymphoma by disrupting autophagy.
The main cause of death for patients with non-Hodgkin lymphoma (NHL) remains therapy resistant relapses. Chemoresistance is commonly associated with apoptosis defects and upregulated autophagy. Therefore, novel therapeutic options that do not rely on apoptosis and target autophagy would be of interest to treat NHL. An agent that may fulfill these requirements is the glycan-binding protein Galectin-9 (Gal-9). A panel of B cell lymphoma NHL cell lines, including diffuse large B cell lymphoma (DLBCL), mantle cell lymphoma (MCL), Burkitt's lymphoma (BL), and (chemoresistant) follicular lymphoma (FL), were treated with Gal-9 after which cell counts and cell viability were determined. Basal mRNA and protein expression levels were respectively determined by RTqPCR and western blot. The impact of Gal-9 treatment on the autophagy pathway was determined using lysotracker, Cyto-ID and western blot (targeting LAMP2, p62, LC3B-I/LC3B-II). Treatment with Gal-9 reduced total cell counts and cell viability of various DLBCL, MCL, BL and FL cell lines. Gal-9-induced cell death was associated with the inhibition of autophagy, as demonstrated by the accumulation of LC3B-II and p62. In addition, Gal-9-sensitive cells expressed lower basal protein levels of LC3B-I as compared to cells that responded less to this lectin. Furthermore, Gal-9 was cytotoxic for chemoresistant Sc-1 cells (Sc-1-RES), which were even more sensitive toward Gal-9 treatment than the parental cells (Sc-1-PAR). Gal-9 is a potent inducer of B cell lymphoma cell dead by inhibiting the proper execution of autophagy.
2025-03-18 | Temporal trends in time toxicity of R-CHOP: a nationwide hospital-based database analysis in Japan.
While the prognosis of patients with cancer has improved, the time burden of treatment has recently been recognized as time toxicity; although, the actual clinical situation remains largely unexplored. This retrospective study aimed to elucidate the time toxicity of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in patients with B-cell lymphoma and the factors influencing it. We used a nationwide hospital-based database between January 2010 and November 2021 in Japan. We extracted the claims data of patients with diffuse large B-cell lymphoma and follicular lymphoma who were hospitalized and/or visited hospitals for chemotherapy. Among the 7760 R-CHOP administered to 2006 patients, the rate of outpatient therapy increased over time (2010-2015: 17.9%; 2016-2021: 31.8%). In 2016, the median length of hospitalization was the shortest at 13 days (IQR 8-19), which coincided with the peak use of pegylated granulocyte colony-stimulating factor (Peg-G-CSF) during hospitalization in 2015-2016, likely driven by changes in the insurance system. In multivariate analysis, the factors associated with longer hospital stays were older age and poor activities of daily living, whereas the use of Peg-G-CSF, a reduced-dose regimen, and treatment at cancer-designated hospitals were associated with shorter stays. The time toxicity of R-CHOP has improved and may be influenced by the patient's condition, adequate supportive care, changes in the insurance system, and center-specific treatment proficiency.
2024-09-08 | Hypogammaglobulinemia and Anti-CD20 Therapy-Induced Acute Thrombocytopenia: Perhaps More than a Coincidence?
The development of secondary hypogammaglobulinemia (sHGG) because of tumor treatment and/or the primary underlying hematologic disorder holds substantial clinical significance. B-cell-derived malignancies and anti-CD20 monoclonal antibodies (mAbs) represent important risk factors for the development of sHGG. In addition, the occurrence of acute thrombocytopenia (AT) induced by anti-CD20 therapy is a known, albeit rare, phenomenon. A 54-year-old patient experiencing the first relapse of classical follicular lymphoma has commenced salvage therapy following the R-DHAP protocol. After rituximab infusion, platelet count dropped from 116 × 109/L to 13 × 109/L within 24 h. Reduced immunoglobulin G levels indicated moderate HGG; thus, we immediately administered intravenous immunoglobulins (IVIg). Within 5 days after initiation of IVIg, platelet count increased and stabilized at >50 × 109/L. It seems possible that anti-CD20 mAbs act like or activate similar mechanisms as autoantibodies in immune thrombocytopenia (ITP). Assuming that anti-CD20 therapy-induced AT is an ITP-like condition, HGG could be considered a potential risk factor. Thus, appropriate treatment of HGG with IVIg prior to anti-CD20 mAb therapy could potentially alleviate anti-CD20 therapy-induced AT.
2024-09-04 | Efficacy and Safety of Bendamustine-Rituximab as Frontline Therapy for Indolent Non-Hodgkin Lymphoma: A Real-World, Single-Center, Retrospective Study.
Background The use of bendamustine with an anti-CD20 monoclonal antibody as frontline therapy for indolent non-Hodgkin lymphoma (NHL) has become a standard of care. We aimed to evaluate the real-world efficacy and safety of bendamustine-rituximab (BR) frontline therapy for indolent NHL. Patients and methods Patients with indolent NHL treated with frontline BR therapy in Hôpital du Sacré-Coeur de Montréal, from January 2015 to August 2018 were included in this retrospective study. Results Our cohort included 42 adults with a median age of 63 years. Follicular lymphoma was the most common histology (n = 31, 74%). Most patients had advanced disease (Lugano stage III or IV, 88%). The overall response rate was 84% (complete response = 62% and partial response = 22%). Median progression-free survival (PFS) was not reached. At 30 months, PFS was 74.8% and overall survival was 90%. Grade 3-4 neutropenia occurred in 21% of patients. Infection-related adverse events were observed in 17 patients (40%). Most were grade 1 and 2 events (84%). One case of grade 5 progressive multifocal leukoencephalopathy related to John Cunningham (JC) virus reactivation was observed. The most common non-infectious-related adverse events were mild nausea and fatigue. Conclusions The efficacy and safety of BR treatment for indolent NHL were comparable in our real-life cohort compared to prior studies. This supports BR as a standard of care for indolent NHL. Future studies should assess whether the use of granulocyte-colony stimulating factors as primary prophylaxis effectively mitigates the hematological and infection-related adverse events related to BR therapy.
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Drug Discovery Landscape
67 orphan drug designations for Follicular lymphoma, including 21 approved therapies.
67 orphan drug designations for Follicular lymphoma, including 21 approved therapies.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
microbiome-based therapeutic peptide cancer immunotherapy composed of 5 synthetic peptides | peptides | FDA | 2026-05-20 | — | Enterome SA |
cell therapy product derived from an allogeneic hematopoietic stem cell donor and expressed anti-CD19 chimeric antigen receptor, T cell receptor of invariant natural killer T cells, and interleukin-15 | cell therapies | FDA | 2026-03-02 | — | Shanghai Allovanta Biotechnology Co., Ltd. |
surovatamig | antibodies | FDA | 2026-02-20 | — | AstraZeneca Pharmaceuticals LP |
small molecule bifunctional cereblon-dependent ligand directed degrader (LDD) of BCL6 | small molecules | FDA | 2026-02-13 | — | Bristol Myers Squibb |
Surovatamig | antibodies | EMA | 2026-01-09 | — | AstraZeneca AB |
allogeneic CRISPR/Cas9-mediated genetically modified CAR T cells targeting CD19 antigen | cell therapies | FDA | 2025-04-04 | — | CRISPR Therapeutics, Inc. |
Tafasitamab [Minjuvi] | antibodies | EMA | 2025-02-26 | 2025-12-16 | Incyte Biosciences Distribution B.V. |
orally available BTK-targeting chimeric degradation activation compound designed to degrade wildtype BTK and multiple mutant forms | small molecules | FDA | 2024-12-17 | — | BeOne Medicines USA, Inc. |
recombinant humanized anti-CD3/CD19 bispecific antibody | antibodies | FDA | 2024-04-22 | — | Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. |
Golcadomide hydrochloride | small molecules | EMA | 2023-12-13 | — | Bristol-Myers Squibb Pharma EEIG |
2-[(3S)-2,6-dioxopiperidin-3-yl]-4-{[(2-fluoro-4-{[3-(morpholin-4-yl)azetidin-1-yl]methyl} phenyl) methyl]amino}-1H-isoindole-1,3(2H)-dione-hydrogen chloride (1/1) | small molecules | FDA | 2023-01-25 | — | Celgene Coporation |
zanubrutinib [Brukinsa] | small molecules | FDA | 2022-11-08 | 2024-03-07 | BeOne Medicines USA, Inc. |
Imvotamab | antibodies | FDA | 2022-10-31 | — | IGM Biosciences, Inc. |
Edited allogeneic chimeric antigen receptor T Cells (CAR-T) | cell therapies | FDA | 2022-09-01 | — | Caribou Biosciences, Inc. |
Odronextamab [Ordspono] | antibodies | EMA | 2022-07-18 | — | Regeneron Ireland Designated Activity Company |
Epcoritamab [Tepkinly] | antibodies | EMA | 2022-06-21 | — | Abbvie Deutschland GmbH & Co. KG |
epcoritamab-bysp [Epkinly] | antibodies | FDA | 2022-03-01 | 2024-06-26 | Genmab US, Inc. |
Anti- FcgammaRIIB Antibody | antibodies | FDA | 2022-01-18 | — | BioInvent International AB |
Mosunetuzumab [Lunsumio] | antibodies | EMA | 2021-11-12 | 2022-06-07 | Roche Registration GmbH |
Zandelisib | small molecules | FDA | 2021-11-09 | — | MEI Pharma, Inc. |
Tisagenlecleucel [Kymriah] | cell therapies | EMA | 2021-07-19 | 2022-05-03 | Novartis Europharm Limited |
an autologous Chimeric Antigen Receptors (CAR) T-cell therapy expressing CD19/CD20 bi-specific CAR | cell therapies | FDA | 2021-05-17 | — | Janssen Research & Development, LLC |
4-{4-{[6-(4-Chlorophenyl)spiro[3.5]non-6-en-7-yl]methyl}-piperazin-1-yl}-N-{{3-nitro-4-[((2S)-1,4-dioxan-2-ylmethyl)amino]phenyl}sulfonyl}-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide | small molecules | FDA | 2021-01-19 | — | Ascentage Pharma Group Inc. |
tafasitamab-cxix [Monjuvi] | antibodies | FDA | 2021-01-07 | 2025-06-18 | Incyte Corporation |
tisagenlecleucel [Kymriah] | cell therapies | FDA | 2020-09-16 | 2022-05-27 | Novartis Pharmaceuticals Corporation |
umbralisib [Ukoniq] | small molecules | FDA | 2020-03-04 | 2021-02-05 | TG Therapeutics, Inc. |
Parsaclisib | small molecules | FDA | 2019-09-25 | — | Incyte Corporation |
apilimod dimesylate | small molecules | FDA | 2019-07-01 | — | AI Therapeutics, Inc. |
6-{[(1R,2S)-2-aminocyclohexyl]amino-7-fluoro-4-(1-methyl-1H-pyrazol-4-yl)-1,2-dihydro-3H-pyrrolo[3,4-c]pyridin-3-one monocitrate | small molecules | FDA | 2019-02-25 | — | Wells Therapeutics, Inc. |
mosunetuzumab-axgb [Lunsumio] | antibodies | FDA | 2018-12-17 | 2022-12-22 | Genentech, Inc. |
mosunetuzumab-axgb [Lunsumio Velo] | antibodies | FDA | 2018-12-17 | 2025-12-19 | Genentech, Inc. |
N-[5-(6-fluoro-8-{[4-(2-hydroxypropan-2-yl)piperidin-1-yl]methyl}-2-morpholinoquinazolin-4-yl)-2-methoxypyridin-3-yl]methanesulfonamide | small molecules | FDA | 2018-10-10 | — | Shanghai Yingli Pharmaceutical Co., Ltd. |
Lisocabtagene maraleucel [Breyanzi] | cell therapies | EMA | 2018-05-25 | — | Bristol-Myers Squibb Pharma EEIG |
Tazemetostat | small molecules | EMA | 2018-03-21 | — | Ipsen Pharma |
avadomide | small molecules | FDA | 2018-03-12 | — | Celgene, a wholly owned subsidiary of Bristol-Myers Squibb |
humanized IgG4-based anti-CD20 x anti-CD3 bispecific monoclonal antibody | antibodies | FDA | 2018-01-25 | — | Regeneron Pharmaceuticals, Inc. |
tazemetostat [Tazverik] | small molecules | FDA | 2017-11-14 | 2020-06-18 | Epizyme, Inc. |
GLUCOPYRANOSYL LIPID A | small molecules | EMA | 2017-10-13 | — | [INACTIVE] Immune Design Limited |
lisocabtagene maraleucel [Breyanzi] | cell therapies | FDA | 2017-09-07 | 2021-02-05 | Juno Therapeutics, Inc., a Bristol-Myers Squibb Company |
pembrolizumab | antibodies | FDA | 2017-06-06 | — | Merck, Sharp & Dohme Corp |
Glucopyranosyl lipid A stable emulsion | small molecules | FDA | 2017-02-14 | — | Immune Design Corp. |
rituximab and recombinant human hyaluronidase [Rituxan SC] | antibodies | FDA | 2016-08-22 | 2017-06-22 | Genentech, Inc. |
axicabtagene ciloleucel [Yescarta] | cell therapies | FDA | 2016-04-25 | 2017-10-18 | Kite Pharma, Inc. |
Autologous T cells transduced with retroviral vector encoding an anti-CD19 CD28/CD3-zeta chimeric antigen receptor [Yescarta] | cell therapies | EMA | 2015-11-11 | 2022-06-23 | Kite Pharma EU B.V. |
daratumumab | antibodies | FDA | 2015-08-06 | — | Janssen Research & Development, LLC |
Obinutuzumab [Gazyvaro] | antibodies | EMA | 2015-06-19 | 2016-06-15 | Roche Registration GmbH |
obinutuzumab [GAZYVA] | antibodies | FDA | 2015-04-15 | 2016-02-26 | Genentech Inc., a member of the Roche Group |
copanlisib [ALIQOPA] | small molecules | FDA | 2015-02-05 | 2017-09-14 | Bayer US LLC |
ibrutinib | small molecules | FDA | 2014-09-08 | — | Pharmacyclics, LLC |
177Lu-tetraxetan-tetulomab | antibodies | EMA | 2014-06-04 | — | Nordic Nanovector AS |
177Lu-tetraxetan-tetulomab | antibodies | FDA | 2014-05-14 | — | Nordic Nanovector AS |
Ibrutinib [Imbruvica] | small molecules | EMA | 2013-12-18 | — | Janssen Cilag International |
idelalisib [Zydelig] | small molecules | FDA | 2013-09-26 | 2014-07-23 | Gilead Sciences, Inc. |
lenalidomide [Revlimid] | small molecules | FDA | 2013-09-17 | 2019-05-28 | Celgene Corporation |
duvelisib [COPIKTRA] | small molecules | FDA | 2013-08-01 | 2018-09-24 | Secura Bio, Inc. |
Duvelisib [Copiktra] | small molecules | EMA | 2013-07-17 | — | [INACTIVE] Verastem Europe GmbH |
Idelalisib | small molecules | EMA | 2013-07-17 | — | Gilead Sciences International Limited |
Lenalidomide [Revlimid] | small molecules | EMA | 2013-01-24 | — | Celgene Europe B.V. |
humanized IgG1 monoclonal anti-CD20 antibody | antibodies | FDA | 2011-05-26 | — | MENTRIK Biotech, LLC |
bortezomib | small molecules | FDA | 2011-01-04 | — | Millennium Pharmaceuticals, Inc. |
dasiprotimut-T | vaccines | FDA | 2009-10-28 | — | Biovest International, Inc. |
4, 5 dibromorhodamine methyl ester | small molecules | FDA | 2008-10-30 | — | Kiadis Pharma Netherlands B.V. |
pralatrexate | small molecules | FDA | 2008-10-20 | — | Acrotech Biopharma LLC |
Autologous tumor-derived immunoglobulin idiotype coupled to keyhole limpet haemocyanin | proteins | EMA | 2006-08-28 | — | Biovest Europe Limited |
Recombinant histidine-tagged idiotype immunoglobulin Fab fragment of clonal B-cell receptors | proteins | EMA | 2004-12-23 | — | CellGenix GmbH |
IODINE (131I) TOSITUMOMAB [Beximab] | other | EMA | 2003-02-14 | — | Glaxosmithkline Research & Development Limited |
IODINE (131I) TOSITUMOMAB [Beximab] | antibodies | EMA | 2003-02-14 | — | Glaxosmithkline Research & Development Limited |
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