RARE DISEASE
Splenic marginal zone lymphoma
Splenic marginal zone lymphoma
Splenic marginal zone lymphoma
Synonyms: SMZL
Synonyms: SMZL
Synonyms: SMZL
Drug discovery
12
drugs
With orphan designations
Overview
Splenic marginal zone lymphoma (SMZL) is a rare, indolent B-cell non-Hodgkin lymphoma primarily involving the spleen, bone marrow, and peripheral blood. It presents with splenomegaly, cytopenias, and lymphocytosis (often with villous lymphocytes). Diagnosis requires excluding morphologic mimics through immunophenotyping (CD5−, CD10−, CD20+). Approximately 20-30% of cases associate with hepatitis C virus. While median survival exceeds 10 years, 10-20% transform to diffuse large B-cell lymphoma (DLBCL), and 30% experience aggressive disease. First-line therapy typically involves rituximab ± chemotherapy, with splenectomy reserved for select cases [1][3][5][14].
Burden
Prognosis: 5-year survival 77%, declining to 60% at 10 years; DLBCL transformation reduces median survival to <4 years [7][14][17].
Morbidity: Splenomegaly-related complications (pain, cytopenias) in 70% of patients; autoimmune manifestations in 20% [1][5][14].
Challenges: Lack of randomized trials due to rarity, relapse rates >50%, and morbidity risks from splenectomy [3][8][18].
Therapies
Asymptomatic/low tumor burden: Observation with monitoring [5][11][16].
Symptomatic disease: Rituximab monotherapy (90% response rate) ± maintenance; splenectomy for bulky splenomegaly/cytopenias in surgical candidates [3][8][13].
High-risk/transformed disease: Rituximab-chemo combinations (e.g., R-bendamustine) or novel agents (e.g., zanubrutinib for relapsed/refractory cases) [10][11][14].
Categories: rare hematological diseases, rare neoplastic diseases, rare transplant-related disorders
Research Papers
355 drug discovery papers about Splenic marginal zone lymphoma, with 1 first-in-class and 6 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
355 drug discovery papers about Splenic marginal zone lymphoma, with 1 first-in-class and 6 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-09-01 | Trends in Survival of Marginal Zone Lymphoma by Treatment Era in the United States
ABSTRACT Marginal zone lymphoma (MZL) comprises three biologically and clinically distinct subtypes. Prior population-based studies have demonstrated improving survival trends for extranodal (EMZL) and nodal (NMZL) subtypes, but not for splenic MZL (SMZL); however, these analyses largely predate the use of novel targeted therapies. Using the SEER-17 database, we identified 40,438 adults diagnosed with MZL between 2000 and 2023. Patients were stratified by diagnosis era: 2000–2008 (rituximab era), 2009–2016 (bendamustine era), and 2017–2023 (novel therapies era). Three-year age-standardized relative survival (RS) was estimated using the Pohar-Perme method. Cumulative incidence of MZL-specific death and death from other causes were estimated using Gray's method, and adjusted subdistribution hazard ratios (SHR) were obtained from Fine-Gray models. Three-year RS improved across eras for all subtypes: EMZL (91.9% to 93.8% to 94.9%), NMZL (85.4% to 89.1% to 90.7%), and SMZL (87.1% to 89.9% to 90.5%). The 5-year cumulative incidence of MZL-specific death for the overall cohort decreased from 12.1% (2000–2008) to 9.2% (2009–2016) and 8.4% (2017–2023, P <0.001), while death from other causes remained stable across eras (P=0.308). In adjusted models, patients diagnosed in 2017–2023 had approximately half the risk of MZL-specific death compared to 2000–2008 (SHR=0.52, 95%CI=0.48–0.57), with consistent improvements across all subtypes (interaction P=0.319). MZL-specific survival has improved steadily across all three subtypes from 2000 to 2023, including SMZL where prior analyses had shown no improvement. The gains were not attributable to a single therapeutic introduction, suggesting a cumulative benefit of evolving management strategies.
2026-08-25 | Real-world effectiveness and safety of Zanubrutinib in Spanish patients with relapsed/refractory marginal zone lymphoma.
There is no established standard treatment of relapsed/refractory (R/R) marginal zone lymphoma (MZL). Zanubrutinib was approved in this setting based on the phase II MAGNOLIA trial. We retrospectively evaluated the characteristics and outcomes of 118 real-world patients in Spain with R/R MZL treated with zanubrutinib after at least one prior anti-CD20-based regimen. The median age at zanubrutinib initiation was 75 years, and 56% were female. MZL subtypes included splenic (55.3%), MALT (18.9%), nodal (19.8%), and non-classifiable (6%). The median number of prior lines of therapy (LoT) was 1.5 (range 1-7); 26% were refractory to the immediately preceding line, and 59% were POD24 to frontline. Thirty-one patients (26.3%) would not have met MAGNOLIA eligibility criteria, 68% had cardiovascular comorbidities, and 28% were receiving antithrombotic therapy. The overall and complete response rates were 76% and 22.2%, respectively, with no differences according to MZL subtype, age, POD24, or MAGNOLIA eligibility. Fewer prior LoT were associated with higher and deeper responses. With a median follow-up of 14 months, 1-year progression-free and overall survival were 79.4% and 86.8%, respectively. Zanubrutinib responders and patients with stable disease presented better outcomes than cases with progressing disease (p < 0.01). Adverse events (AEs) were reported in 34.1% of patients (grade ≥ 3 in 14.4%). MAGNOLIA-ineligible patients experienced a higher incidence of AEs, and bleeding events were more frequent among patients receiving anticoagulant therapy (p = 0.04). Overall, zanubrutinib demonstrated favorable effectiveness and safety in real-world R/R MZL, with improved outcomes when administered earlier in the disease.
2026-03-23 | Marginal Zone Lymphoma: 2026 Update on Diagnosis and Management.
Marginal zone lymphoma (MZL) is a heterogeneous group of indolent mature B-cell neoplasms with classically three major subtypes: nodal, splenic, and extranodal MZL of mucosa-associated lymphoid tissue (MALT). Diagnosis and disease evaluation of MZL is further advanced by the use of genomic testing and PET/CT with emerging evidence for the use of circulating tumor DNA. The RECLASS classification system proposed a hierarchical approach to classifying MZL while the FIL-NF10 investigators introduced a fourth MZL subtype, disseminated MZL. Though the prognosis of MZL varies between subtypes and stages, the MZL IPI and FLIPI24 indices can be used for prognostication. Frontline treatment of MZL varies between localized disease and advanced-stage diseases. The former favor the use of local therapies such as radiotherapy and anti-microbial in certain subtypes with a selective role of rituximab monotherapy. The latter requires systemic immunotherapy ± chemotherapy with emerging data for cytotoxic-free and covalent Bruton tyrosine kinase inhibitor (cBTKi)-based regimens. cBTKi and immunomodulators are established in relapsed/refractory MZL, while data for antibody-drug conjugates, T-cell engagers, and potentially CAR T-cell therapies are maturing.
2026-02-04 | Indolent Lymphomas and Leukemia
This study examines the clinical characteristics and outcomes of dogs diagnosed with splenic marginal zone lymphoma (SMZL). Drawing on a retrospective review of medical records from 56 dogs treated between 2000 and 2010, the analysis focuses on survival times, treatment protocols, and adverse events. The findings indicate that SMZL in dogs is generally indolent, with a median survival time exceeding 1000 days post-diagnosis. However, significant variability in outcomes is observed based on treatment modalities, with chemotherapy and surgical intervention yielding differing efficacy. The study highlights the importance of individualized treatment plans, as dogs receiving combination therapies demonstrated improved progression-free survival compared to those treated with single-agent protocols. Additionally, the research identifies specific clinical markers, such as the presence of B-cell receptor rearrangements, which correlate with better responses to therapy. The implications of these findings underscore the need for further prospective studies to standardize treatment guidelines and optimize patient outcomes in canine SMZL.
2025-11-03 | Genetic analysis and clinical correlations in marginal zone lymphoma
Abstract Background: Marginal zone lymphoma (MZL) is a heterogeneous group of indolent B-cell malignancies with distinct molecular landscapes across its subtypes (extranodal/MALT, splenic, nodal, and disseminate). Genetic characteristics of MZL and its clinical relevance were not well defined. This study aims to explore subtype-specific genetic signatures and their clinical correlations in a retro-prospective MZL cohort Methods: We retrospectively analyzed MZL patients who underwent targeted Next-Generation Sequencing(NGS) panel for lymphoproliferative disorders at our institution and examining their mutational profiles and correlations with clinical characteristics and outcomes. Results:From December 2017 and August 2024, 136 MZL patients with NGS testing results underwent systemic treatment in our center. The median age was 63 years (range 30–92) and the male-to-female ratio was 1.1. This cohort comprised 52(38.2%) MALT/EMZL, 7(5.2%) NMZL, 65 (47.8%)SMZL and 12(8.8%) dissMZL patients, respectively. The most frequently detected mutations were MYD88L265P(13.2%),TP53 (12.5%), CXCR4 (6.6%), DNMT3A (6.6%), EP300 (6.6%), TET2 (5.9%),TNFAIP3 (5.1%)，in descending order of frequency. No associations were found between mutations and clinical features such as Ann Arbor stage or MZL-IPI. However, patients with large B cell transformation showed higher frequencies of EP300 (22.2% vs. 4.3%, p=0.019) and EZH2 (11.1% vs. 0.1%, p=0.017) mutations. TNFAIP3 mutations varied significantly across subtypes: 0% (MALT/EMZL), 14.3% (NMZL), 9.2% (SMZL), and 0% (dissMZL) (p=0.045). With median follow-up of 65.3months(range 2.2-262), the 5-year PFS and OS rates were 46.1% (95% CI 36.8–57.5) and 85.2% (78.5–92.4), respectively. Progression of disease within 24 months was observed in 27.4% of patients. TP53 mutations adversely impacted OS (HR 2.85, 95% CI 1.17–6.95; p=0.014) but not PFS. No other mutations predicted survival. Conclusion: This study delineates the distinct mutational landscape of MZL, revealing subtype-specific patterns (TNFAIP3 variation) and transformation-associated alterations (EP300/EZH2). The adverse impact of TP53 mutations on OS underscores its prognostic value, while the 27.4% POD24 rate highlights unmet needs in high-risk subsets. These findings advocate for integrating molecular profiling (particularly TP53, EP300, and TNFAIP3) with clinical indices like MZL-IPI to refine risk stratification and guide targeted therapy development in MZL.
proteins
2026-05-01 | C32-21 Unmasking the Swell: Recurrent Acquired Angioedema as a Manifestation of Marginal Zone Lymphoma
Abstract Introduction Acquired angioedema (AAE) due to C1-esterase inhibitor (C1-INH) deficiency is a rare, potentially fatal disorder caused by increased bradykinin activity leading to vascular permeability and submucosal edema. Unlike hereditary angioedema, AAE typically presents later in life, lacks a family history, and is frequently associated with underlying B-cell lymphoproliferative disorders or autoimmune diseases. Among these, splenic marginal zone lymphoma (MZL) is disproportionately represented, highlighting a paraneoplastic link between complement consumption and tumor activity. Because bradykinin-mediated angioedema does not respond to epinephrine, corticosteroids, or antihistamines, recognition and disease-specific management are crucial to avoid airway compromise. Case Description A 65-year-old woman with newly diagnosed splenic MZL presented with her third episode of sudden tongue swelling now accompanied by progressive dysarthria, drooling, and respiratory distress. In the emergency department, she was administered 1g intravenous (IV) Tranexamic acid, 20 mg IV Famotidine, 50 mg IV Diphenhydramine, and 125 mg IV Methylprednisolone without improvement. Worsening edema necessitated emergent endotracheal intubation for impending airway obstruction.In the intensive care unit, she was treated with intravenous corticosteroids, diphenhydramine, famotidine, and received two units of fresh frozen plasma. Complement studies revealed a low C1q level (<2 mg/dL), and markedly reduced C1 esterase inhibitor assay ( 7%), confirming acquired C1-INH deficiency. C4 level was also depressed, and autoimmune serologies were negative. Following stabilization, she self-extubated without rebound swelling and was discharged with hematology follow-up for ongoing lymphoma-directed therapy and referral to Allergy-Immunology. Discussion This case underscores a rare but clinically significant manifestation of AAE in the setting of splenic MZL. Adult-onset, recurrent, non-pruritic angioedema unresponsive to conventional histaminergic therapies should prompt evaluation for bradykinin-mediated etiologies. Diagnostic confirmation relies on complement testing, specifically, low C1q and C1-INH levels with normal C1-INH gene sequence, distinguishing AAE from hereditary forms. Acute management centers on airway protection and targeted therapy such as plasma-derived or recombinant C1-INH, icatibant (a bradykinin B2-receptor antagonist), or ecallantide (a kallikrein inhibitor), when available. FFP remains a pragmatic option in resource-limited settings. Long-term control depends on treating the underlying lymphoproliferative disorder, which can normalize complement levels and prevent recurrence.Heightened clinical awareness of AAE in patients with unexplained angioedema and concurrent B-cell malignancies can prevent morbidity and mortality through timely diagnosis and multidisciplinary management. This abstract is funded by: none
2025-11-03 | A phase II investigator-initiated frontline trial of evorpacept (ALX148), lenalidomide and rituximab for high tumor burden indolent b-cell non-Hodgkin lymphoma
Abstract Introduction . We have recently completed a phase I trial of evorpacept (formerly known as ALX148), a novel high-affinity signal regulatory protein (SIRP)a fusion protein that blocks cluster of differentiation (CD)47, in combination with lenalidomide and rituximab (R2) in patients with relapsed refractory indolent B-cell non-Hodgkin lymphoma (iNHL). The combination was safe, no dose limiting toxicity was observed at a dose of 60 mg/Kg on day (D) 1 of a 28-day cycle, and more than 80% of patients experienced a complete response (CR). We present here a phase 2 study investigating the efficacy of this regimen in patients with previously untreated and high tumor burden iNHL. Methods. This single arm phase II study (NCT05025800) was conducted between January and November 2025 (data cut-off 07/2025). Adult patients with previously untreated and advanced stage iNHL, who met indication for treatment according to The Groupe d'Etude des Lymphomes Folliculaires (GELF) criteria were included. Evorpacept was administered intravenously (IV), in a 28-day cycle, for 6 cycles, at the recommended phase 2 dose of 60 mg/Kg on D1; rituximab IV was given weekly during cycle 1, and on D1 during cycles 2-6; lenalidomide was given orally on D1-21 during cycles 1-6. Toxicity was evaluated according to Common Terminology Criteria for Adverse Events (CTCAE) version 5. The primary endpoint was best CR rate per Lugano 2014 criteria. Results. Twenty-four patients were included in the study, and all were evaluable for safety and efficacy. Median age was 64 (33-76) and 13 (54%) were male; 14 (58%) had follicular lymphoma, including 5 patients with grade 3A, and 10 (42%) had marginal zone lymphoma (MZL), including 4 with extra-nodal, 4 with nodal, and 2 with splenic subtype; median largest lymph node size was 3.6 cm (range, 1.5-7.5 cm), median maximum standardized uptake volume was 7.1 (range, 3-32), and all patients had intermediate-high Follicular Lymphoma International Prognostic Index (FLIPI). Median number of cycles was 6 (range, 3-6), and all patients had completed treatment at time of data cut-off. The most common (> 1 patient) grade 3-4 adverse events included: neutropenia (29%), all resolved with growth factor, infections (12.5%), alanine transferase (ALT) increase (12.5%), aspartate transferase (AST) increase (12.5%), and infusion related reaction (8%). Ten (42%) patients required a dose reduction in lenalidomide, mainly due to infections, but none in evorpacept; 2 (8%) patients discontinued lenalidomide and 1 (4%) evorpacept, due to AST/ALT elevation. Twenty-two (92%) patients achieved CR, 2 (8%) partial response, and overall response rate was 100%. After a median follow-up of 10 months (95% confidence interval, 9-12 months), 2 patients have progressed (1 with likely baseline transformed MZL), with a 1-year progression-free survival rate of 87%. At most recent follow-up no patients have died, and 1-year overall survival rate was 100%. Conclusions. The addition of evorpacept to R2 is a safe and effective frontline non-chemotherapy regimen for iNHL patients, resulting in high CR rates. While longer follow-up matures, serial blood samples are being evaluated for circulating tumor DNA by phased variant enrichment and detection sequencing (PhasED-seq) to determine the minimal residual disease eradication rate with this novel regimen.
2020-09-30 | Splenic Hematopoietic and Stromal Cells in Cancer Progression
Tumor-derived secretory factors orchestrate splenic hematopoietic and stromal cells to fuel metastasis. The spleen acts as a reservoir site for hematopoietic stem and progenitor cells, which are rapidly exploited as myeloid-derived suppressor cells at the cost of tumor-reactive lymphoid cells. Splenic erythroid progenitor cells and mesenchymal stromal cells contribute directly and indirectly to both tumor immune escape and the metastatic cascade. Animal models provide valuable mechanistic insights, but their translation to a clinical setting highlights specific challenges and open issues. In this review, we envision the exploitation of the spleen as a source for novel biomarkers and therapeutic approaches.
2020-07-01 | Marginal zone lymphoma expression of histidine‐rich glycoprotein correlates with improved survival
The abundant hepatocyte-expressed plasma protein histidine-rich glycoprotein (HRG) enhances antitumor immunity by polarizing inflammatory and immune cells in several mouse models, however, the clinical relevance of HRG in human cancer is poorly explored. The expression and role of HRG in human B-cell lymphomas was investigated in order to find new tools for prognosis and treatment.Immunohistochemical (IHC) analysis and RNA hybridization of tissue microarrays showed that (i) HRG was expressed by tumor cells in marginal zone lymphoma (MZL), in 36% of 59 cases. Expression was also detected in follicular lymphoma (22%), mantle cell lymphoma (19%), and indiffuse large B-cell lymphoma (DLBCL;5%) while primary CNS lymphoma (PCNSL) lacked expression of HRG. (ii) MZL patients positive for HRG showed a superior overall survival outcome (HR = 0.086, 95% CI = 0.014-0.518, P-value = .007), indicating a protective role for HRG independent of stage, age and sex. (iii) HRG-expressing MZL displayed significantly increased transcript and protein levels of the host defense peptide alpha defensin 1. In addition, global transcript analyses showed significant changes in gene ontology terms relating to immunity and inflammation, however, infiltration of immune and inflammatory cells detected by IHC was unaffected by HRG expression.HRG expression by MZL tumor cells correlates with an altered transcription profile and improved overall survival.
2015-02-02 | Success of interferon α therapy in a patient with hepatitis C virus-negative splenic marginal zone lymphoma associated with polycythemia vera
Splenic marginal zone lymphoma (SMZL) is a rare indolent lymphoma accounting for fewer than 1% of non-Hodgkin lymphomas. This chronic lymphoproliferative disorder (LPD) is characterized by spleen e...
cell therapies
2026-02-16 | Lisocabtagene maraleucel in patients with relapsed or refractory marginal zone lymphoma (TRANSCEND FL): primary analysis results from the global, multicohort, single-arm, phase 2 study.
Effective treatments with deep and durable responses for relapsed or refractory marginal zone lymphoma (MZL) are lacking. The objective of the primary analysis from the MZL cohort of TRANSCEND FL was to evaluate the efficacy and safety of the CD19-directed chimeric antigen receptor (CAR) T-cell therapy lisocabtagene maraleucel. In this phase 2, single-arm, multicohort study, patients from 30 sites in the USA, Canada, Europe, and Japan with relapsed or refractory MZL who had at least two previous lines of systemic therapy were eligible to receive lisocabtagene maraleucel (100 × 106 CAR+ T cells). Bridging therapy was allowed. The primary endpoint was overall response rate per independent review committee by CT by use of Lugano 2014 criteria (null hypothesis ≤50%). This study is registered with ClinicalTrials.gov, NCT04245839, and is ongoing. Of 77 leukapheresed patients recruited between November 11, 2020, and August 24, 2023, 67 received lisocabtagene maraleucel and 66 were efficacy evaluable. MZL subtypes included nodal (n=32 [48%]), splenic (n=18 [27%]), and extranodal-mucosa-associated lymphoid tissue (n=17 [25%]). Median (IQR) previous lines of systemic therapy was 3 (2-4). Median on-study follow-up was 24·1 months. The primary endpoint was met, with an overall response rate of 95% (n=63; 95% CI, 87·3-99·1; one-sided p<0·0001). All patients experienced a treatment-related adverse event. Grade 3 cytokine release syndrome or neurological events occurred in three (4%) patients each (no grade 4-5 events). 11 (16%) patients had grade ≥3 infections: six (9%) patients during the 90-day treatment-emergent period and seven (10%) during the post-treatment-emergent period. In patients with relapsed or refractory MZL, lisocabtagene maraleucel showed high rates of durable responses. The safety profile was manageable, with no new safety signals. These results support lisocabtagene maraleucel as a new treatment option for patients with relapsed or refractory MZL. Celgene, a Bristol-Myers Squibb Company.
2023-08-31 | IBCL-318 Epidemiological, Clinical, Histopathologic and Therapeutic Characteristics of Marginal Zone Lymphoma: Experience of the Hematology Department of Casablanca in Morocco
factors impairing T-cell function in sMZL.Our findings highlight the importance of maintaining healthy T-cell pools as a predictor of long-term disease-free intervals and support a rationale for earlier use of T-cell-based therapies.
2018-07-09 | High‐dose therapy and autologous stem cell transplantation in marginal zone lymphomas: a retrospective study by the EBMT Lymphoma Working Party and FIL‐GITMO
The role of autologous stem cell transplantation (ASCT) in patients with marginal zone lymphoma (MZL) is debatable. This study investigated the outcome and prognostic factors affecting the outcome of patients undergoing ASCT for MZL. Eligible patients had non-transformed nodal, extra-nodal (MALT) or splenic MZL (SMZL), aged ≥18 years, who underwent a first ASCT between1994 and 2013 and were reported to the European Society for Blood and Marrow Transplantation, Fondazione Italiana Linfomi or Gruppo Italiano Trapianto Di Midollo Osseo registries. The study included 199 patients, [111 MALT lymphoma, 55 nodal MZL (NMZL) and 33 SMZL]. Median age at transplantation was 56 years. The median number of prior therapies was 2 (range 1-8), including rituximab in 71%. 95% had chemosensitive disease. 89% received a chemotherapy-based high-dose regimen. There were no significant differences in patient and transplant characteristics between the 3 histological subtypes except for a lower percentage of patients previously treated with rituximab in the MALT sub-group and more transplants performed in recent years in the other sub-groups. After a median follow-up of 5 years, 5-year cumulative incidence of relapse/progression and non-relapse mortality were 38% and 9%, respectively. Five-year event-free survival (EFS) and overall survival (OS) were 53% and 73%, respectively. Five-year cumulative incidence of second malignancies was 6%. Multivariate analysis revealed age ≥65 years was associated with a shorter EFS and OS. In addition, patients with SMZL had a shorter OS than those with MALT. ASCT may provide clinical benefit in MZL patients who have failed multiple lines of chemoimmunotherapy.
2018-03-23 | Allogeneic hematopoietic cell transplant for relapsed-refractory, marginal zone lymphoma: a single-center experience
A subset of marginal zone lymphoma (MZL) has an aggressive clinical course and role of allogeneic hematopoietic cell transplant (allo-HCT) is not well defined for these patients. MZL includes three...
2017-02-22 | Role of Allogeneic Stem Cell Transplantation in Aggressive Marginal Zone Lymphoma—Single Center Experience
Introduction: Marginal zone B cell lymphoma (MZBCL) is a non-Hodgkin lymphoma, which usually behaves in an indolent manner. However, a subset of patients with this lymphoma has an aggressive clinical course characterized by advanced stage of disease, resistance to standard therapies, and rapid progression. Role of allogeneic-SCT (allo-SCT) is not well defined in management of this subtype of non-Hodgkin lymphoma. We performed a single-institution retrospective study to assess the therapeutic outcomes of allo-SCT in relapsed/refractory MZBCL. Methods: We identified the patients with biopsy-proven MZBCL and aggressive clinical course, who underwent allo-SCT at our institution between 2001 and 2013. Patient's clinical and treatment data was collected by comprehensive chart review. Cases complicated by second malignancy and transformed lymphoma were excluded. Results: A total of six patients with MZBCL underwent allo-SCT during the study period. The median age was 49 years and the median follow-up period was 88.9 months. Five patients had relapsed/refractory disease and one had primary refractory disease. Patients had a median of 3 prior therapies before allo-SCT. The pathology was extranodal MZBCL in 3 patients, splenic MZBCL in 2 patients and nodal MZBCL in 1 patient. Four patients presented with Ann Arbor stage IV disease, and other two with stage II and III each. Rituximab-based chemoimmunotherapy was the first-line treatment in 4 patients and the other two patients received rituximab alone. Three patients achieved complete response to the initial treatment with median progression free survival (PFS) of 7 months. Table 1 shows therapeutic outcomes of first line treatments and allo-SCT. Four patients had reduced intensity conditioning (RIC) and two patients received myeloablative conditioning. Calcineurin inhibitor (CNI) based graft versus host disease (GVHD) prophylaxis was used in all patients. Median survival from the allo-SCT and overall survival (OS) from the diagnosis were 77.8 months and 98 months (Figure 1). No relapses were identified post allo-SCT during the study period. No statistically significant correlation was seen between OS and age, type of MZBCL (extranodal versus splenic), PFS with first-line therapy, or type of conditioning regimen. Incidence of acute and chronic GVHD was 60% and 20%. Two patients remained disease-free and alive at 96.9 and 77.8 months from the date of allo-SCT. Two patients died of infection during the follow-up period.Table 1Initial treatment and allo-SCT outcomes of the patients with MZBCLFigure 1Overall survival of the patients with MZBCL who underwent allo-SCT.View Large Image Figure ViewerDownload Hi-res image Download (PPT) Conclusion: MZBCL appears to be quite sensitive to graft versus lymphoma effect. Our findings indicate that allo-SCT is feasible with reasonable transplant related mortality in this difficult-to-treat patient population and should be considered in eligible patients.
antibodies
2026-08-31 | Survival after first relapse in marginal zone lymphomas: Prospective data from the international observational NF10 study.
While marginal zone lymphoma (MZL) is generally indolent, outcomes following relapse remain poorly defined. This study utilized the indolent Non Follicular 10 (NF10) prospective database to characterize survival and identify prognostic drivers in patients failing initial systemic therapy. The study analysed 122 patients with relapsed MZL. The primary end-point was progression-free survival from first relapse (2PFS), with survival after relapse (SAR) as the secondary end-point. The median 2PFS was 24 months, with a 2-year 2PFS rate of 49% and a 2-year SAR rate of 66%. Multivariable analysis identified advanced age, progression of disease within 24 months (POD24) and high MZL International Prognostic Index (MZL-IPI) scores as significant predictors of inferior survival. Patients with splenic and disseminated subtypes also demonstrated worse outcomes. Relapse following systemic therapy often marks a transition to an aggressive clinical course. Time to progression and the MZL-IPI are robust tools for risk stratification, highlighting an urgent need for novel therapeutic strategies for high-risk relapsed MZL populations.
2026-07-17 | Acquired Hemophilia A Revealing Occult Splenic Marginal Zone Lymphoma.
BACKGROUND Acquired hemophilia A is a rare autoimmune bleeding disorder caused by inhibitory autoantibodies against coagulation factor VIII and is associated with significant morbidity and mortality. Although malignancy-associated acquired hemophilia A is well recognized, its presentation as the initial manifestation of an otherwise clinically subtle indolent B-cell lymphoma, such as splenic marginal zone lymphoma, remains exceedingly uncommon. We report a case highlighting the importance of recognizing acquired factor VIII inhibitors, evaluating for underlying lymphoproliferative disorders, and the potential role of rituximab monotherapy in achieving control of both the inhibitor and the underlying lymphoma. CASE REPORT A 77-year-old man presented with spontaneous bruising and an isolated prolonged activated partial thromboplastin time that failed to correct on mixing studies. Further evaluation demonstrated markedly reduced factor VIII activity, a factor VIII inhibitor, diffuse splenomegaly, and flow cytometry and bone marrow biopsy findings most consistent with splenic marginal zone lymphoma. Treatment with activated prothrombin complex concentrate, corticosteroids, and rituximab resulted in normalization of coagulation parameters, recovery of factor VIII activity, decline in inhibitor titers, resolution of bleeding manifestations, and sustained clinical stability without recurrent bleeding or evidence of lymphoma progression. CONCLUSIONS This case highlights acquired hemophilia A as a rare paraneoplastic manifestation of splenic marginal zone lymphoma and emphasizes the importance of evaluating for an underlying lymphoproliferative disorder in older adults presenting with newly identified factor VIII inhibitors, particularly in the setting of cytopenias or splenomegaly. It also demonstrates that rituximab-based therapy can effectively achieve sustained remission of both the inhibitor and the underlying indolent lymphoma.
2026-06-17 | Splenic Marginal Zone Lymphoma Presenting with Progressive Splenic Infarction and Acute Cholestatic Liver Injury- a Case Report
Abstract Background Splenic marginal zone lymphoma (SMZL) is a rare, indolent non-Hodgkin lymphoma. Progressive splenic infarction and acute cholestatic liver injury are uncommon complications, and their concurrent presentation has not been previously reported. Case Description A 76-year-old woman with remote breast cancer history and chronic splenomegaly with pancytopenia presented with worsening left-sided abdominal pain. Labs revealed pancytopenia and cholestatic liver injury. CT demonstrated a 22-cm spleen with multiple wedge-shaped infarcts and mildly heterogeneous hepatic enhancement. PET/CT showed diffuse splenic hypermetabolism, hypermetabolic periportal lymph nodes, and mildly increased bone marrow FDG uptake. Hemolysis workup including direct antiglobulin test and cold agglutinin titer was negative. Hepatitis B and C serologies were negative. D-dimer was markedly elevated at 3,840 ng/mL. MRCP excluded biliary obstruction. Percutaneous splenic core biopsy revealed nodular and intrasinusoidal infiltration by atypical B lymphocytes. Immunohistochemistry showed CD20, PAX5, and IgM positivity with kappa restriction; CD5, CD10, CD23, CD103, and cyclin D1 were negative. CD21 highlighted follicular dendritic cell meshworks colonized by neoplastic cells. The patient was staged as Ann Arbor stage IV. Rituximab monotherapy was initiated with clinical improvement. At 6-month follow-up, liver function normalized, cytopenias resolved, splenic size decreased from 22 to 17 cm, and PET/CT demonstrated partial metabolic response. Significance This is the first reported case of SMZL with concurrent splenic infarction and cholestatic liver injury. It highlights the diagnostic utility of splenic core biopsy with an expanded immunohistochemical panel and the efficacy of rituximab monotherapy in this clinical context.
2026-05-13 | Beyond Hypersplenism: Splenic Marginal Zone Lymphoma in an Older Adult with Hemoglobin E/Beta-Thalassemia.
With improvements in blood safety and availability, along with broad access to safe and effective iron chelation, outcomes for patients with thalassemia have greatly improved over recent decades. Previously a predominantly pediatric condition, thalassemia is now increasingly encountered in an aging population. We describe an adult man with HbE/β-thalassemia whose course was complicated by progressive splenomegaly and cytopenias, initially attributed to his underlying thalassemia. Further evaluation, however, revealed splenic marginal zone lymphoma. After the initiation of anti-B-cell therapy, he experienced rapid clinical improvement and was able to avoid surgical splenectomy. This case highlights how complications ascribed to thalassemia can overlap with other diagnoses that may become more prevalent with age, and demonstrates the importance of maintaining a broad differential when symptoms progress despite appropriate thalassemia-directed management.
2026-05-01 | B53-11 Refractory Antiphospholipid Syndrome Presenting as a Splenic Infarct and Mesenteric Mass - A Challenging Diagnosis
Abstract Introduction Antiphospholipid syndrome (APS) is an autoimmune prothrombotic disorder that often affects young women. It is recognized by the presence of antiphospholipid antibodies, including anticardiolipin antibodies (aCL), lupus anticoagulant (LA), and anti-beta-2-glycoprotein I (aβ2GPI) antibodies in the setting of venous or arterial thrombosis or pregnancy morbidity. APS can be primary or secondary to autoimmune diseases, drugs, infections, or malignancy. Clinicians should maintain a high index of suspicion for secondary APS, especially in older patients or those with progressive thrombosis despite adequate anticoagulation. This report presents an anticoagulant-refractory case of APS in a 60-year-old woman that was ultimately driven by an underlying lymphoproliferative disorder. Case Presentation A 60-year-old woman with hypertension, atrial fibrillation, chronic obstructive pulmonary disease (COPD), obstructive sleep apnea (OSA), gout, gastroesophageal reflux disease (GERD), and fatty liver disease presented with left upper quadrant abdominal pain associated with nausea, vomiting, and early satiety. A computerized tomography (CT) scan revealed splenomegaly with splenic infarcts. Coagulation studies showed a normal prothrombin time (PT), prolonged activated partial thromboplastin time (aPTT), and mild thrombocytopenia. The mixing study demonstrated persistently elevated aPTT. Complete blood count showed anemia and leukopenia. Haptoglobin was low, complement level was normal, and antinuclear antibody (ANA) was elevated. Autoimmune serology confirmed persistently elevated aCL, elevated aβ2GPI antibody, and LA. Since diagnosis, her course was marked by failure to respond to a direct oral anticoagulant and subsequently to warfarin, as evidenced by progressive splenomegaly and the appearance of new splenic infarcts. She was therefore transitioned to subcutaneous enoxaparin, but her symptoms did not improve. Repeat imaging showed a new enhancing right lower mesenteric mass of unclear etiology. Peripheral blood smear showed relative lymphocytosis, although the morphology was not diagnostic for chronic lymphocytic leukemia. Flow cytometry demonstrated involvement by a CD5-negative, CD10-negative kappa-restricted B-cell lymphoproliferative disorder. Bone marrow biopsy confirmed a monotypic CD5-negative, CD10-negative B-cell population most consistent with splenic marginal zone lymphoma. Discussion Late-onset APS that continues to cause recurrent arterial and venous thrombosis with organ infarction despite appropriate anticoagulation should raise suspicion for a secondary driver, including a paraneoplastic process. In this patient, the refractory thrombotic behavior was related to an underlying lymphoproliferative disorder. Adequate anticoagulation could not be achieved without addressing the driving malignancy. She was started on rituximab 375 mg/m² intravenously (IV) weekly in addition to therapeutic enoxaparin 80 mg subcutaneously twice daily and aspirin 81 mg daily, resulting in clinical improvement. This abstract is funded by: None
other
2025-09-22 | A hidden clue behind angioedema in an elderly patient.
Acquired angioedema (AAE) is a rare, potentially life-threatening condition caused by bradykinin, typically presenting as recurrent, non-pitting facial swelling without urticaria. Unlike hereditary forms, acquired angioedema arises later in life and may be associated with underlying B-cell lymphoproliferative disorders. We report a 62-year-old woman with persistent antihistamine-unresponsive facial angioedema, fatigue, and moderate splenomegaly, which led to further work-up for AAE. Low C4 and C1 inhibitor (C1-INH) was detected, with normal C1q levels. Given the presence of splenomegaly and cytopenia, further evaluation of lymphoproliferative disease was pursued. Bone marrow biopsy confirmed splenic marginal zone lymphoma (SMZL), and rituximab-based chemotherapy resulted in full remission of both lymphoma and angioedema. This case highlights the importance of evaluating elderly patients with unexplained angioedema and organomegaly for hidden lymphoproliferative disease. Treating the underlying disease can resolve symptoms and improve outcomes.
2022-04-30 | Development of an Antigen Delivery System for a B Cell-Targeted Vaccine as an Alternative to Dendritic Cell-Targeted Vaccines
Vaccines have contributed to the prevention of infectious diseases for a long time. Pathogen-derived antigens and adjuvants in vaccine formulations stimulate immune cells to elicit humoral and cellular immune responses against pathogens. Achieving highly immune responses with decreased adverse effects requires the development of a system that can deliver antigens to specific immune cells. Dendritic cells (DCs) are well-known professional antigen presenting cells (APCs) that initiate acquired immune responses by presenting antigens to T cells. Accordingly, DC-targeted vaccines have been investigated and applied in clinical trials for the treatment of infectious diseases and for chronic diseases such as cancers. In addition to DCs, B lymphocytes are regarded as professional APCs despite their primary role in humoral immunity. Therefore, B cell-targeted vaccines are also expected to elicit both humoral and cellular immune responses. In this review we summarize the basic functions of DCs and B cells as APCs. We also provide information on DC and B cell targeted vaccines in preclinical and clinical settings. Finally, we introduce our novel antigen delivery system that targets splenic marginal zone B cells and the ability of this system to act as a novel vaccine that elicits both humoral and cellular immune responses.
small molecules
2026-09-01 | Trends in Survival of Marginal Zone Lymphoma by Treatment Era in the United States
ABSTRACT Marginal zone lymphoma (MZL) comprises three biologically and clinically distinct subtypes. Prior population-based studies have demonstrated improving survival trends for extranodal (EMZL) and nodal (NMZL) subtypes, but not for splenic MZL (SMZL); however, these analyses largely predate the use of novel targeted therapies. Using the SEER-17 database, we identified 40,438 adults diagnosed with MZL between 2000 and 2023. Patients were stratified by diagnosis era: 2000–2008 (rituximab era), 2009–2016 (bendamustine era), and 2017–2023 (novel therapies era). Three-year age-standardized relative survival (RS) was estimated using the Pohar-Perme method. Cumulative incidence of MZL-specific death and death from other causes were estimated using Gray's method, and adjusted subdistribution hazard ratios (SHR) were obtained from Fine-Gray models. Three-year RS improved across eras for all subtypes: EMZL (91.9% to 93.8% to 94.9%), NMZL (85.4% to 89.1% to 90.7%), and SMZL (87.1% to 89.9% to 90.5%). The 5-year cumulative incidence of MZL-specific death for the overall cohort decreased from 12.1% (2000–2008) to 9.2% (2009–2016) and 8.4% (2017–2023, P <0.001), while death from other causes remained stable across eras (P=0.308). In adjusted models, patients diagnosed in 2017–2023 had approximately half the risk of MZL-specific death compared to 2000–2008 (SHR=0.52, 95%CI=0.48–0.57), with consistent improvements across all subtypes (interaction P=0.319). MZL-specific survival has improved steadily across all three subtypes from 2000 to 2023, including SMZL where prior analyses had shown no improvement. The gains were not attributable to a single therapeutic introduction, suggesting a cumulative benefit of evolving management strategies.
2026-08-25 | Real-world effectiveness and safety of Zanubrutinib in Spanish patients with relapsed/refractory marginal zone lymphoma.
There is no established standard treatment of relapsed/refractory (R/R) marginal zone lymphoma (MZL). Zanubrutinib was approved in this setting based on the phase II MAGNOLIA trial. We retrospectively evaluated the characteristics and outcomes of 118 real-world patients in Spain with R/R MZL treated with zanubrutinib after at least one prior anti-CD20-based regimen. The median age at zanubrutinib initiation was 75 years, and 56% were female. MZL subtypes included splenic (55.3%), MALT (18.9%), nodal (19.8%), and non-classifiable (6%). The median number of prior lines of therapy (LoT) was 1.5 (range 1-7); 26% were refractory to the immediately preceding line, and 59% were POD24 to frontline. Thirty-one patients (26.3%) would not have met MAGNOLIA eligibility criteria, 68% had cardiovascular comorbidities, and 28% were receiving antithrombotic therapy. The overall and complete response rates were 76% and 22.2%, respectively, with no differences according to MZL subtype, age, POD24, or MAGNOLIA eligibility. Fewer prior LoT were associated with higher and deeper responses. With a median follow-up of 14 months, 1-year progression-free and overall survival were 79.4% and 86.8%, respectively. Zanubrutinib responders and patients with stable disease presented better outcomes than cases with progressing disease (p < 0.01). Adverse events (AEs) were reported in 34.1% of patients (grade ≥ 3 in 14.4%). MAGNOLIA-ineligible patients experienced a higher incidence of AEs, and bleeding events were more frequent among patients receiving anticoagulant therapy (p = 0.04). Overall, zanubrutinib demonstrated favorable effectiveness and safety in real-world R/R MZL, with improved outcomes when administered earlier in the disease.
2026-03-23 | Marginal Zone Lymphoma: 2026 Update on Diagnosis and Management.
Marginal zone lymphoma (MZL) is a heterogeneous group of indolent mature B-cell neoplasms with classically three major subtypes: nodal, splenic, and extranodal MZL of mucosa-associated lymphoid tissue (MALT). Diagnosis and disease evaluation of MZL is further advanced by the use of genomic testing and PET/CT with emerging evidence for the use of circulating tumor DNA. The RECLASS classification system proposed a hierarchical approach to classifying MZL while the FIL-NF10 investigators introduced a fourth MZL subtype, disseminated MZL. Though the prognosis of MZL varies between subtypes and stages, the MZL IPI and FLIPI24 indices can be used for prognostication. Frontline treatment of MZL varies between localized disease and advanced-stage diseases. The former favor the use of local therapies such as radiotherapy and anti-microbial in certain subtypes with a selective role of rituximab monotherapy. The latter requires systemic immunotherapy ± chemotherapy with emerging data for cytotoxic-free and covalent Bruton tyrosine kinase inhibitor (cBTKi)-based regimens. cBTKi and immunomodulators are established in relapsed/refractory MZL, while data for antibody-drug conjugates, T-cell engagers, and potentially CAR T-cell therapies are maturing.
2026-02-04 | Indolent Lymphomas and Leukemia
This study examines the clinical characteristics and outcomes of dogs diagnosed with splenic marginal zone lymphoma (SMZL). Drawing on a retrospective review of medical records from 56 dogs treated between 2000 and 2010, the analysis focuses on survival times, treatment protocols, and adverse events. The findings indicate that SMZL in dogs is generally indolent, with a median survival time exceeding 1000 days post-diagnosis. However, significant variability in outcomes is observed based on treatment modalities, with chemotherapy and surgical intervention yielding differing efficacy. The study highlights the importance of individualized treatment plans, as dogs receiving combination therapies demonstrated improved progression-free survival compared to those treated with single-agent protocols. Additionally, the research identifies specific clinical markers, such as the presence of B-cell receptor rearrangements, which correlate with better responses to therapy. The implications of these findings underscore the need for further prospective studies to standardize treatment guidelines and optimize patient outcomes in canine SMZL.
2025-11-03 | Genetic analysis and clinical correlations in marginal zone lymphoma
Abstract Background: Marginal zone lymphoma (MZL) is a heterogeneous group of indolent B-cell malignancies with distinct molecular landscapes across its subtypes (extranodal/MALT, splenic, nodal, and disseminate). Genetic characteristics of MZL and its clinical relevance were not well defined. This study aims to explore subtype-specific genetic signatures and their clinical correlations in a retro-prospective MZL cohort Methods: We retrospectively analyzed MZL patients who underwent targeted Next-Generation Sequencing(NGS) panel for lymphoproliferative disorders at our institution and examining their mutational profiles and correlations with clinical characteristics and outcomes. Results:From December 2017 and August 2024, 136 MZL patients with NGS testing results underwent systemic treatment in our center. The median age was 63 years (range 30–92) and the male-to-female ratio was 1.1. This cohort comprised 52(38.2%) MALT/EMZL, 7(5.2%) NMZL, 65 (47.8%)SMZL and 12(8.8%) dissMZL patients, respectively. The most frequently detected mutations were MYD88L265P(13.2%),TP53 (12.5%), CXCR4 (6.6%), DNMT3A (6.6%), EP300 (6.6%), TET2 (5.9%),TNFAIP3 (5.1%)，in descending order of frequency. No associations were found between mutations and clinical features such as Ann Arbor stage or MZL-IPI. However, patients with large B cell transformation showed higher frequencies of EP300 (22.2% vs. 4.3%, p=0.019) and EZH2 (11.1% vs. 0.1%, p=0.017) mutations. TNFAIP3 mutations varied significantly across subtypes: 0% (MALT/EMZL), 14.3% (NMZL), 9.2% (SMZL), and 0% (dissMZL) (p=0.045). With median follow-up of 65.3months(range 2.2-262), the 5-year PFS and OS rates were 46.1% (95% CI 36.8–57.5) and 85.2% (78.5–92.4), respectively. Progression of disease within 24 months was observed in 27.4% of patients. TP53 mutations adversely impacted OS (HR 2.85, 95% CI 1.17–6.95; p=0.014) but not PFS. No other mutations predicted survival. Conclusion: This study delineates the distinct mutational landscape of MZL, revealing subtype-specific patterns (TNFAIP3 variation) and transformation-associated alterations (EP300/EZH2). The adverse impact of TP53 mutations on OS underscores its prognostic value, while the 27.4% POD24 rate highlights unmet needs in high-risk subsets. These findings advocate for integrating molecular profiling (particularly TP53, EP300, and TNFAIP3) with clinical indices like MZL-IPI to refine risk stratification and guide targeted therapy development in MZL.
proteins
2026-05-01 | C32-21 Unmasking the Swell: Recurrent Acquired Angioedema as a Manifestation of Marginal Zone Lymphoma
Abstract Introduction Acquired angioedema (AAE) due to C1-esterase inhibitor (C1-INH) deficiency is a rare, potentially fatal disorder caused by increased bradykinin activity leading to vascular permeability and submucosal edema. Unlike hereditary angioedema, AAE typically presents later in life, lacks a family history, and is frequently associated with underlying B-cell lymphoproliferative disorders or autoimmune diseases. Among these, splenic marginal zone lymphoma (MZL) is disproportionately represented, highlighting a paraneoplastic link between complement consumption and tumor activity. Because bradykinin-mediated angioedema does not respond to epinephrine, corticosteroids, or antihistamines, recognition and disease-specific management are crucial to avoid airway compromise. Case Description A 65-year-old woman with newly diagnosed splenic MZL presented with her third episode of sudden tongue swelling now accompanied by progressive dysarthria, drooling, and respiratory distress. In the emergency department, she was administered 1g intravenous (IV) Tranexamic acid, 20 mg IV Famotidine, 50 mg IV Diphenhydramine, and 125 mg IV Methylprednisolone without improvement. Worsening edema necessitated emergent endotracheal intubation for impending airway obstruction.In the intensive care unit, she was treated with intravenous corticosteroids, diphenhydramine, famotidine, and received two units of fresh frozen plasma. Complement studies revealed a low C1q level (<2 mg/dL), and markedly reduced C1 esterase inhibitor assay ( 7%), confirming acquired C1-INH deficiency. C4 level was also depressed, and autoimmune serologies were negative. Following stabilization, she self-extubated without rebound swelling and was discharged with hematology follow-up for ongoing lymphoma-directed therapy and referral to Allergy-Immunology. Discussion This case underscores a rare but clinically significant manifestation of AAE in the setting of splenic MZL. Adult-onset, recurrent, non-pruritic angioedema unresponsive to conventional histaminergic therapies should prompt evaluation for bradykinin-mediated etiologies. Diagnostic confirmation relies on complement testing, specifically, low C1q and C1-INH levels with normal C1-INH gene sequence, distinguishing AAE from hereditary forms. Acute management centers on airway protection and targeted therapy such as plasma-derived or recombinant C1-INH, icatibant (a bradykinin B2-receptor antagonist), or ecallantide (a kallikrein inhibitor), when available. FFP remains a pragmatic option in resource-limited settings. Long-term control depends on treating the underlying lymphoproliferative disorder, which can normalize complement levels and prevent recurrence.Heightened clinical awareness of AAE in patients with unexplained angioedema and concurrent B-cell malignancies can prevent morbidity and mortality through timely diagnosis and multidisciplinary management. This abstract is funded by: none
2025-11-03 | A phase II investigator-initiated frontline trial of evorpacept (ALX148), lenalidomide and rituximab for high tumor burden indolent b-cell non-Hodgkin lymphoma
Abstract Introduction . We have recently completed a phase I trial of evorpacept (formerly known as ALX148), a novel high-affinity signal regulatory protein (SIRP)a fusion protein that blocks cluster of differentiation (CD)47, in combination with lenalidomide and rituximab (R2) in patients with relapsed refractory indolent B-cell non-Hodgkin lymphoma (iNHL). The combination was safe, no dose limiting toxicity was observed at a dose of 60 mg/Kg on day (D) 1 of a 28-day cycle, and more than 80% of patients experienced a complete response (CR). We present here a phase 2 study investigating the efficacy of this regimen in patients with previously untreated and high tumor burden iNHL. Methods. This single arm phase II study (NCT05025800) was conducted between January and November 2025 (data cut-off 07/2025). Adult patients with previously untreated and advanced stage iNHL, who met indication for treatment according to The Groupe d'Etude des Lymphomes Folliculaires (GELF) criteria were included. Evorpacept was administered intravenously (IV), in a 28-day cycle, for 6 cycles, at the recommended phase 2 dose of 60 mg/Kg on D1; rituximab IV was given weekly during cycle 1, and on D1 during cycles 2-6; lenalidomide was given orally on D1-21 during cycles 1-6. Toxicity was evaluated according to Common Terminology Criteria for Adverse Events (CTCAE) version 5. The primary endpoint was best CR rate per Lugano 2014 criteria. Results. Twenty-four patients were included in the study, and all were evaluable for safety and efficacy. Median age was 64 (33-76) and 13 (54%) were male; 14 (58%) had follicular lymphoma, including 5 patients with grade 3A, and 10 (42%) had marginal zone lymphoma (MZL), including 4 with extra-nodal, 4 with nodal, and 2 with splenic subtype; median largest lymph node size was 3.6 cm (range, 1.5-7.5 cm), median maximum standardized uptake volume was 7.1 (range, 3-32), and all patients had intermediate-high Follicular Lymphoma International Prognostic Index (FLIPI). Median number of cycles was 6 (range, 3-6), and all patients had completed treatment at time of data cut-off. The most common (> 1 patient) grade 3-4 adverse events included: neutropenia (29%), all resolved with growth factor, infections (12.5%), alanine transferase (ALT) increase (12.5%), aspartate transferase (AST) increase (12.5%), and infusion related reaction (8%). Ten (42%) patients required a dose reduction in lenalidomide, mainly due to infections, but none in evorpacept; 2 (8%) patients discontinued lenalidomide and 1 (4%) evorpacept, due to AST/ALT elevation. Twenty-two (92%) patients achieved CR, 2 (8%) partial response, and overall response rate was 100%. After a median follow-up of 10 months (95% confidence interval, 9-12 months), 2 patients have progressed (1 with likely baseline transformed MZL), with a 1-year progression-free survival rate of 87%. At most recent follow-up no patients have died, and 1-year overall survival rate was 100%. Conclusions. The addition of evorpacept to R2 is a safe and effective frontline non-chemotherapy regimen for iNHL patients, resulting in high CR rates. While longer follow-up matures, serial blood samples are being evaluated for circulating tumor DNA by phased variant enrichment and detection sequencing (PhasED-seq) to determine the minimal residual disease eradication rate with this novel regimen.
2020-09-30 | Splenic Hematopoietic and Stromal Cells in Cancer Progression
Tumor-derived secretory factors orchestrate splenic hematopoietic and stromal cells to fuel metastasis. The spleen acts as a reservoir site for hematopoietic stem and progenitor cells, which are rapidly exploited as myeloid-derived suppressor cells at the cost of tumor-reactive lymphoid cells. Splenic erythroid progenitor cells and mesenchymal stromal cells contribute directly and indirectly to both tumor immune escape and the metastatic cascade. Animal models provide valuable mechanistic insights, but their translation to a clinical setting highlights specific challenges and open issues. In this review, we envision the exploitation of the spleen as a source for novel biomarkers and therapeutic approaches.
2020-07-01 | Marginal zone lymphoma expression of histidine‐rich glycoprotein correlates with improved survival
The abundant hepatocyte-expressed plasma protein histidine-rich glycoprotein (HRG) enhances antitumor immunity by polarizing inflammatory and immune cells in several mouse models, however, the clinical relevance of HRG in human cancer is poorly explored. The expression and role of HRG in human B-cell lymphomas was investigated in order to find new tools for prognosis and treatment.Immunohistochemical (IHC) analysis and RNA hybridization of tissue microarrays showed that (i) HRG was expressed by tumor cells in marginal zone lymphoma (MZL), in 36% of 59 cases. Expression was also detected in follicular lymphoma (22%), mantle cell lymphoma (19%), and indiffuse large B-cell lymphoma (DLBCL;5%) while primary CNS lymphoma (PCNSL) lacked expression of HRG. (ii) MZL patients positive for HRG showed a superior overall survival outcome (HR = 0.086, 95% CI = 0.014-0.518, P-value = .007), indicating a protective role for HRG independent of stage, age and sex. (iii) HRG-expressing MZL displayed significantly increased transcript and protein levels of the host defense peptide alpha defensin 1. In addition, global transcript analyses showed significant changes in gene ontology terms relating to immunity and inflammation, however, infiltration of immune and inflammatory cells detected by IHC was unaffected by HRG expression.HRG expression by MZL tumor cells correlates with an altered transcription profile and improved overall survival.
2015-02-02 | Success of interferon α therapy in a patient with hepatitis C virus-negative splenic marginal zone lymphoma associated with polycythemia vera
Splenic marginal zone lymphoma (SMZL) is a rare indolent lymphoma accounting for fewer than 1% of non-Hodgkin lymphomas. This chronic lymphoproliferative disorder (LPD) is characterized by spleen e...
cell therapies
2026-02-16 | Lisocabtagene maraleucel in patients with relapsed or refractory marginal zone lymphoma (TRANSCEND FL): primary analysis results from the global, multicohort, single-arm, phase 2 study.
Effective treatments with deep and durable responses for relapsed or refractory marginal zone lymphoma (MZL) are lacking. The objective of the primary analysis from the MZL cohort of TRANSCEND FL was to evaluate the efficacy and safety of the CD19-directed chimeric antigen receptor (CAR) T-cell therapy lisocabtagene maraleucel. In this phase 2, single-arm, multicohort study, patients from 30 sites in the USA, Canada, Europe, and Japan with relapsed or refractory MZL who had at least two previous lines of systemic therapy were eligible to receive lisocabtagene maraleucel (100 × 106 CAR+ T cells). Bridging therapy was allowed. The primary endpoint was overall response rate per independent review committee by CT by use of Lugano 2014 criteria (null hypothesis ≤50%). This study is registered with ClinicalTrials.gov, NCT04245839, and is ongoing. Of 77 leukapheresed patients recruited between November 11, 2020, and August 24, 2023, 67 received lisocabtagene maraleucel and 66 were efficacy evaluable. MZL subtypes included nodal (n=32 [48%]), splenic (n=18 [27%]), and extranodal-mucosa-associated lymphoid tissue (n=17 [25%]). Median (IQR) previous lines of systemic therapy was 3 (2-4). Median on-study follow-up was 24·1 months. The primary endpoint was met, with an overall response rate of 95% (n=63; 95% CI, 87·3-99·1; one-sided p<0·0001). All patients experienced a treatment-related adverse event. Grade 3 cytokine release syndrome or neurological events occurred in three (4%) patients each (no grade 4-5 events). 11 (16%) patients had grade ≥3 infections: six (9%) patients during the 90-day treatment-emergent period and seven (10%) during the post-treatment-emergent period. In patients with relapsed or refractory MZL, lisocabtagene maraleucel showed high rates of durable responses. The safety profile was manageable, with no new safety signals. These results support lisocabtagene maraleucel as a new treatment option for patients with relapsed or refractory MZL. Celgene, a Bristol-Myers Squibb Company.
2023-08-31 | IBCL-318 Epidemiological, Clinical, Histopathologic and Therapeutic Characteristics of Marginal Zone Lymphoma: Experience of the Hematology Department of Casablanca in Morocco
factors impairing T-cell function in sMZL.Our findings highlight the importance of maintaining healthy T-cell pools as a predictor of long-term disease-free intervals and support a rationale for earlier use of T-cell-based therapies.
2018-07-09 | High‐dose therapy and autologous stem cell transplantation in marginal zone lymphomas: a retrospective study by the EBMT Lymphoma Working Party and FIL‐GITMO
The role of autologous stem cell transplantation (ASCT) in patients with marginal zone lymphoma (MZL) is debatable. This study investigated the outcome and prognostic factors affecting the outcome of patients undergoing ASCT for MZL. Eligible patients had non-transformed nodal, extra-nodal (MALT) or splenic MZL (SMZL), aged ≥18 years, who underwent a first ASCT between1994 and 2013 and were reported to the European Society for Blood and Marrow Transplantation, Fondazione Italiana Linfomi or Gruppo Italiano Trapianto Di Midollo Osseo registries. The study included 199 patients, [111 MALT lymphoma, 55 nodal MZL (NMZL) and 33 SMZL]. Median age at transplantation was 56 years. The median number of prior therapies was 2 (range 1-8), including rituximab in 71%. 95% had chemosensitive disease. 89% received a chemotherapy-based high-dose regimen. There were no significant differences in patient and transplant characteristics between the 3 histological subtypes except for a lower percentage of patients previously treated with rituximab in the MALT sub-group and more transplants performed in recent years in the other sub-groups. After a median follow-up of 5 years, 5-year cumulative incidence of relapse/progression and non-relapse mortality were 38% and 9%, respectively. Five-year event-free survival (EFS) and overall survival (OS) were 53% and 73%, respectively. Five-year cumulative incidence of second malignancies was 6%. Multivariate analysis revealed age ≥65 years was associated with a shorter EFS and OS. In addition, patients with SMZL had a shorter OS than those with MALT. ASCT may provide clinical benefit in MZL patients who have failed multiple lines of chemoimmunotherapy.
2018-03-23 | Allogeneic hematopoietic cell transplant for relapsed-refractory, marginal zone lymphoma: a single-center experience
A subset of marginal zone lymphoma (MZL) has an aggressive clinical course and role of allogeneic hematopoietic cell transplant (allo-HCT) is not well defined for these patients. MZL includes three...
2017-02-22 | Role of Allogeneic Stem Cell Transplantation in Aggressive Marginal Zone Lymphoma—Single Center Experience
Introduction: Marginal zone B cell lymphoma (MZBCL) is a non-Hodgkin lymphoma, which usually behaves in an indolent manner. However, a subset of patients with this lymphoma has an aggressive clinical course characterized by advanced stage of disease, resistance to standard therapies, and rapid progression. Role of allogeneic-SCT (allo-SCT) is not well defined in management of this subtype of non-Hodgkin lymphoma. We performed a single-institution retrospective study to assess the therapeutic outcomes of allo-SCT in relapsed/refractory MZBCL. Methods: We identified the patients with biopsy-proven MZBCL and aggressive clinical course, who underwent allo-SCT at our institution between 2001 and 2013. Patient's clinical and treatment data was collected by comprehensive chart review. Cases complicated by second malignancy and transformed lymphoma were excluded. Results: A total of six patients with MZBCL underwent allo-SCT during the study period. The median age was 49 years and the median follow-up period was 88.9 months. Five patients had relapsed/refractory disease and one had primary refractory disease. Patients had a median of 3 prior therapies before allo-SCT. The pathology was extranodal MZBCL in 3 patients, splenic MZBCL in 2 patients and nodal MZBCL in 1 patient. Four patients presented with Ann Arbor stage IV disease, and other two with stage II and III each. Rituximab-based chemoimmunotherapy was the first-line treatment in 4 patients and the other two patients received rituximab alone. Three patients achieved complete response to the initial treatment with median progression free survival (PFS) of 7 months. Table 1 shows therapeutic outcomes of first line treatments and allo-SCT. Four patients had reduced intensity conditioning (RIC) and two patients received myeloablative conditioning. Calcineurin inhibitor (CNI) based graft versus host disease (GVHD) prophylaxis was used in all patients. Median survival from the allo-SCT and overall survival (OS) from the diagnosis were 77.8 months and 98 months (Figure 1). No relapses were identified post allo-SCT during the study period. No statistically significant correlation was seen between OS and age, type of MZBCL (extranodal versus splenic), PFS with first-line therapy, or type of conditioning regimen. Incidence of acute and chronic GVHD was 60% and 20%. Two patients remained disease-free and alive at 96.9 and 77.8 months from the date of allo-SCT. Two patients died of infection during the follow-up period.Table 1Initial treatment and allo-SCT outcomes of the patients with MZBCLFigure 1Overall survival of the patients with MZBCL who underwent allo-SCT.View Large Image Figure ViewerDownload Hi-res image Download (PPT) Conclusion: MZBCL appears to be quite sensitive to graft versus lymphoma effect. Our findings indicate that allo-SCT is feasible with reasonable transplant related mortality in this difficult-to-treat patient population and should be considered in eligible patients.
antibodies
2026-08-31 | Survival after first relapse in marginal zone lymphomas: Prospective data from the international observational NF10 study.
While marginal zone lymphoma (MZL) is generally indolent, outcomes following relapse remain poorly defined. This study utilized the indolent Non Follicular 10 (NF10) prospective database to characterize survival and identify prognostic drivers in patients failing initial systemic therapy. The study analysed 122 patients with relapsed MZL. The primary end-point was progression-free survival from first relapse (2PFS), with survival after relapse (SAR) as the secondary end-point. The median 2PFS was 24 months, with a 2-year 2PFS rate of 49% and a 2-year SAR rate of 66%. Multivariable analysis identified advanced age, progression of disease within 24 months (POD24) and high MZL International Prognostic Index (MZL-IPI) scores as significant predictors of inferior survival. Patients with splenic and disseminated subtypes also demonstrated worse outcomes. Relapse following systemic therapy often marks a transition to an aggressive clinical course. Time to progression and the MZL-IPI are robust tools for risk stratification, highlighting an urgent need for novel therapeutic strategies for high-risk relapsed MZL populations.
2026-07-17 | Acquired Hemophilia A Revealing Occult Splenic Marginal Zone Lymphoma.
BACKGROUND Acquired hemophilia A is a rare autoimmune bleeding disorder caused by inhibitory autoantibodies against coagulation factor VIII and is associated with significant morbidity and mortality. Although malignancy-associated acquired hemophilia A is well recognized, its presentation as the initial manifestation of an otherwise clinically subtle indolent B-cell lymphoma, such as splenic marginal zone lymphoma, remains exceedingly uncommon. We report a case highlighting the importance of recognizing acquired factor VIII inhibitors, evaluating for underlying lymphoproliferative disorders, and the potential role of rituximab monotherapy in achieving control of both the inhibitor and the underlying lymphoma. CASE REPORT A 77-year-old man presented with spontaneous bruising and an isolated prolonged activated partial thromboplastin time that failed to correct on mixing studies. Further evaluation demonstrated markedly reduced factor VIII activity, a factor VIII inhibitor, diffuse splenomegaly, and flow cytometry and bone marrow biopsy findings most consistent with splenic marginal zone lymphoma. Treatment with activated prothrombin complex concentrate, corticosteroids, and rituximab resulted in normalization of coagulation parameters, recovery of factor VIII activity, decline in inhibitor titers, resolution of bleeding manifestations, and sustained clinical stability without recurrent bleeding or evidence of lymphoma progression. CONCLUSIONS This case highlights acquired hemophilia A as a rare paraneoplastic manifestation of splenic marginal zone lymphoma and emphasizes the importance of evaluating for an underlying lymphoproliferative disorder in older adults presenting with newly identified factor VIII inhibitors, particularly in the setting of cytopenias or splenomegaly. It also demonstrates that rituximab-based therapy can effectively achieve sustained remission of both the inhibitor and the underlying indolent lymphoma.
2026-06-17 | Splenic Marginal Zone Lymphoma Presenting with Progressive Splenic Infarction and Acute Cholestatic Liver Injury- a Case Report
Abstract Background Splenic marginal zone lymphoma (SMZL) is a rare, indolent non-Hodgkin lymphoma. Progressive splenic infarction and acute cholestatic liver injury are uncommon complications, and their concurrent presentation has not been previously reported. Case Description A 76-year-old woman with remote breast cancer history and chronic splenomegaly with pancytopenia presented with worsening left-sided abdominal pain. Labs revealed pancytopenia and cholestatic liver injury. CT demonstrated a 22-cm spleen with multiple wedge-shaped infarcts and mildly heterogeneous hepatic enhancement. PET/CT showed diffuse splenic hypermetabolism, hypermetabolic periportal lymph nodes, and mildly increased bone marrow FDG uptake. Hemolysis workup including direct antiglobulin test and cold agglutinin titer was negative. Hepatitis B and C serologies were negative. D-dimer was markedly elevated at 3,840 ng/mL. MRCP excluded biliary obstruction. Percutaneous splenic core biopsy revealed nodular and intrasinusoidal infiltration by atypical B lymphocytes. Immunohistochemistry showed CD20, PAX5, and IgM positivity with kappa restriction; CD5, CD10, CD23, CD103, and cyclin D1 were negative. CD21 highlighted follicular dendritic cell meshworks colonized by neoplastic cells. The patient was staged as Ann Arbor stage IV. Rituximab monotherapy was initiated with clinical improvement. At 6-month follow-up, liver function normalized, cytopenias resolved, splenic size decreased from 22 to 17 cm, and PET/CT demonstrated partial metabolic response. Significance This is the first reported case of SMZL with concurrent splenic infarction and cholestatic liver injury. It highlights the diagnostic utility of splenic core biopsy with an expanded immunohistochemical panel and the efficacy of rituximab monotherapy in this clinical context.
2026-05-13 | Beyond Hypersplenism: Splenic Marginal Zone Lymphoma in an Older Adult with Hemoglobin E/Beta-Thalassemia.
With improvements in blood safety and availability, along with broad access to safe and effective iron chelation, outcomes for patients with thalassemia have greatly improved over recent decades. Previously a predominantly pediatric condition, thalassemia is now increasingly encountered in an aging population. We describe an adult man with HbE/β-thalassemia whose course was complicated by progressive splenomegaly and cytopenias, initially attributed to his underlying thalassemia. Further evaluation, however, revealed splenic marginal zone lymphoma. After the initiation of anti-B-cell therapy, he experienced rapid clinical improvement and was able to avoid surgical splenectomy. This case highlights how complications ascribed to thalassemia can overlap with other diagnoses that may become more prevalent with age, and demonstrates the importance of maintaining a broad differential when symptoms progress despite appropriate thalassemia-directed management.
2026-05-01 | B53-11 Refractory Antiphospholipid Syndrome Presenting as a Splenic Infarct and Mesenteric Mass - A Challenging Diagnosis
Abstract Introduction Antiphospholipid syndrome (APS) is an autoimmune prothrombotic disorder that often affects young women. It is recognized by the presence of antiphospholipid antibodies, including anticardiolipin antibodies (aCL), lupus anticoagulant (LA), and anti-beta-2-glycoprotein I (aβ2GPI) antibodies in the setting of venous or arterial thrombosis or pregnancy morbidity. APS can be primary or secondary to autoimmune diseases, drugs, infections, or malignancy. Clinicians should maintain a high index of suspicion for secondary APS, especially in older patients or those with progressive thrombosis despite adequate anticoagulation. This report presents an anticoagulant-refractory case of APS in a 60-year-old woman that was ultimately driven by an underlying lymphoproliferative disorder. Case Presentation A 60-year-old woman with hypertension, atrial fibrillation, chronic obstructive pulmonary disease (COPD), obstructive sleep apnea (OSA), gout, gastroesophageal reflux disease (GERD), and fatty liver disease presented with left upper quadrant abdominal pain associated with nausea, vomiting, and early satiety. A computerized tomography (CT) scan revealed splenomegaly with splenic infarcts. Coagulation studies showed a normal prothrombin time (PT), prolonged activated partial thromboplastin time (aPTT), and mild thrombocytopenia. The mixing study demonstrated persistently elevated aPTT. Complete blood count showed anemia and leukopenia. Haptoglobin was low, complement level was normal, and antinuclear antibody (ANA) was elevated. Autoimmune serology confirmed persistently elevated aCL, elevated aβ2GPI antibody, and LA. Since diagnosis, her course was marked by failure to respond to a direct oral anticoagulant and subsequently to warfarin, as evidenced by progressive splenomegaly and the appearance of new splenic infarcts. She was therefore transitioned to subcutaneous enoxaparin, but her symptoms did not improve. Repeat imaging showed a new enhancing right lower mesenteric mass of unclear etiology. Peripheral blood smear showed relative lymphocytosis, although the morphology was not diagnostic for chronic lymphocytic leukemia. Flow cytometry demonstrated involvement by a CD5-negative, CD10-negative kappa-restricted B-cell lymphoproliferative disorder. Bone marrow biopsy confirmed a monotypic CD5-negative, CD10-negative B-cell population most consistent with splenic marginal zone lymphoma. Discussion Late-onset APS that continues to cause recurrent arterial and venous thrombosis with organ infarction despite appropriate anticoagulation should raise suspicion for a secondary driver, including a paraneoplastic process. In this patient, the refractory thrombotic behavior was related to an underlying lymphoproliferative disorder. Adequate anticoagulation could not be achieved without addressing the driving malignancy. She was started on rituximab 375 mg/m² intravenously (IV) weekly in addition to therapeutic enoxaparin 80 mg subcutaneously twice daily and aspirin 81 mg daily, resulting in clinical improvement. This abstract is funded by: None
other
2025-09-22 | A hidden clue behind angioedema in an elderly patient.
Acquired angioedema (AAE) is a rare, potentially life-threatening condition caused by bradykinin, typically presenting as recurrent, non-pitting facial swelling without urticaria. Unlike hereditary forms, acquired angioedema arises later in life and may be associated with underlying B-cell lymphoproliferative disorders. We report a 62-year-old woman with persistent antihistamine-unresponsive facial angioedema, fatigue, and moderate splenomegaly, which led to further work-up for AAE. Low C4 and C1 inhibitor (C1-INH) was detected, with normal C1q levels. Given the presence of splenomegaly and cytopenia, further evaluation of lymphoproliferative disease was pursued. Bone marrow biopsy confirmed splenic marginal zone lymphoma (SMZL), and rituximab-based chemotherapy resulted in full remission of both lymphoma and angioedema. This case highlights the importance of evaluating elderly patients with unexplained angioedema and organomegaly for hidden lymphoproliferative disease. Treating the underlying disease can resolve symptoms and improve outcomes.
2022-04-30 | Development of an Antigen Delivery System for a B Cell-Targeted Vaccine as an Alternative to Dendritic Cell-Targeted Vaccines
Vaccines have contributed to the prevention of infectious diseases for a long time. Pathogen-derived antigens and adjuvants in vaccine formulations stimulate immune cells to elicit humoral and cellular immune responses against pathogens. Achieving highly immune responses with decreased adverse effects requires the development of a system that can deliver antigens to specific immune cells. Dendritic cells (DCs) are well-known professional antigen presenting cells (APCs) that initiate acquired immune responses by presenting antigens to T cells. Accordingly, DC-targeted vaccines have been investigated and applied in clinical trials for the treatment of infectious diseases and for chronic diseases such as cancers. In addition to DCs, B lymphocytes are regarded as professional APCs despite their primary role in humoral immunity. Therefore, B cell-targeted vaccines are also expected to elicit both humoral and cellular immune responses. In this review we summarize the basic functions of DCs and B cells as APCs. We also provide information on DC and B cell targeted vaccines in preclinical and clinical settings. Finally, we introduce our novel antigen delivery system that targets splenic marginal zone B cells and the ability of this system to act as a novel vaccine that elicits both humoral and cellular immune responses.
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Drug Discovery Landscape
12 orphan drug designations for Splenic marginal zone lymphoma, including 5 approved therapies.
12 orphan drug designations for Splenic marginal zone lymphoma, including 5 approved therapies.
Drug | Therapy type | Orphan designation | Clinical trial status | Sponsor |
|---|---|---|---|---|
odronextamab | antibodies | FDA | Regeneron Pharmaceuticals, Inc. | |
tafasitamab-cxix | antibodies | FDA | Incyte Corporation | |
lisocabtagene maraleucel [Breyanzi] | cell therapies | FDA | Approved | Juno Therapeutics, Inc., a Bristol-Myers Squibb Company |
zanubrutinib [Brukinsa] | small molecules | FDA | Approved | BeOne Medicines USA, Inc. |
parsaclisib | small molecules | FDA | Incyte Corporation | |
umbralisib [Ukoniq] | small molecules | FDA | Approved | TG Therapeutics, Inc. |
obinutuzumab | antibodies | FDA | Genentech Inc., a member of the Roche Group | |
copanlisib | small molecules | FDA | Bayer HealthCare Pharmaceuticals, Inc. | |
lenalidomide [Revlimid] | small molecules | FDA | Approved | Celgene Corporation |
obinutuzumab | antibodies | FDA | Genentech, Inc. | |
ibrutinib [Imbruvica] | small molecules | FDA | Approved | Pharmacyclics, LLC |
idelalisib | small molecules | FDA | Gilead Sciences, Inc. |
“Terminated” – programs with discontinued clinical trials, or with no updates reported for 5 years after completion or 12 years after the last trial started.
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