2026-07-16 | Malignancy-Associated Hemophagocytic Lymphohistiocytosis: Clinical Characteristics, Treatment Patterns, and Survival Outcomes in a Tertiary Care Center Cohort.
Malignancy-associated hemophagocytic lymphohistiocytosis (M-HLH) carries a poor prognosis and is often complicated by overlapping infection, cytopenias, organ failure, and progressive disease. We retrospectively analyzed 49 adults with M-HLH at a single tertiary cancer center (2013-2026), summarizing malignancy spectrum, diagnostic features, treatment, and survival outcomes. HLH probability was assessed by HScore and modified HLH-2004 criteria. Lymphoma was the main underlying disease (34/49; 69.4%), led by aggressive B-cell (17/49; 34.7%) and T-cell NHL (12/49; 24.5%). HLH coincided with initial malignancy recognition in 17 of 49 patients (34.7%). The median HScore was 231 (IQR 202-256); 44 of 49 patients (89.8%) met the ≥ 169 threshold, and 42 of 49 patients (85.7%) fulfilled ≥ 5 of 7 modified HLH-2004 criteria. HLH-directed therapy included corticosteroids (41/49; 83.7%), etoposide (21/49; 42.9%), and anakinra (16/49; 32.7%); 21 of 49 patients (42.9%) received concurrent malignancy-directed chemotherapy. Mortality was 59.2% (29/49) with a median overall survival of 56 days (median follow-up 612 days for the cohort; 574 days among survivors, n = 20). De novo presentation carried substantially lower mortality than HLH in previously known malignancy (23.5% vs. 78.1%; hazard ratio [HR] 5.38, 95% confidence interval [CI], 1.85-15.61; P = .002). Malignancy-directed chemotherapy was associated with lower mortality than HLH-directed therapy alone (HR 3.11, 95% CI, 1.36-7.09; P = .007). All 6 patients with invasive mold infection died. M-HLH was predominantly lymphoma-associated, met diagnostic criteria with high probability, and carried poor short-term survival. De novo presentation had better outcomes, likely because lymphoma-directed chemotherapy can simultaneously address the underlying malignant trigger and the hyperinflammatory state. Invasive mold infection was uniformly fatal, illustrating the lethal combination of profound immunosuppression and uncontrolled opportunistic infection in this setting.
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2026-06-23 | Bendamustine-based lymphodepletion prior to CAR T-cell therapy: a systematic review.
Lymphodepletion (LD) is a critical prerequisite for successful chimeric antigen receptor T-cell (CAR-T) therapy. While fludarabine and cyclophosphamide (Flu/Cy) remain the standard LD regimen, bendamustine has emerged as a potential alternative due to its distinct immunomodulatory properties and more favorable toxicity profile. This systematic review evaluates the safety, efficacy, and feasibility of bendamustine-based LD in patients undergoing CAR-T therapy for hematologic malignancies. A comprehensive literature search was conducted through January 2026 across PubMed, Embase, Web of Science, and clinical trial registries. Studies were eligible if they reported clinical outcomes following bendamustine-based lymphodepletion prior to CD19-, CD30-, or BCMA-directed CAR-T therapy. Extracted endpoints included overall response rate (ORR), complete response rate (CRR), progression-free survival (PFS), overall survival (OS), and treatment-related toxicities. Eighteen studies comprising over 1400 patients were included. Across disease indications-including B- and T-cell non-Hodgkin lymphoma, Hodgkin lymphoma (HL), and multiple myeloma (MM)-ORRs ranged from 50% to 88%, with CRRs up to 74%. Compared with Flu/Cy, bendamustine-based LD demonstrated comparable efficacy while being associated with significantly lower rates of cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and grade ≥3 cytopenias. Additionally, bendamustine facilitated outpatient CAR-T delivery, with reduced hospitalization and intensive care unit (ICU) utilization. However, prior exposure to bendamustine before leukapheresis was associated with inferior CAR-T outcomes. Bendamustine-based LD represents a safe and effective alternative to Flu/Cy, particularly in outpatient settings and in patients at higher risk of treatment-related toxicity. However, the current evidence is largely derived from retrospective and non-randomized studies. Prospective, comparative trials are warranted to validate these findings and to better define the optimal LD strategy across disease types and CAR-T platforms.
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2026-06-15 | A rare collision tumor of lymphoepithelioma-like carcinoma and t-cell lymphoma: a case report.
We report a rare case of a collision tumor in a patient concurrently diagnosed with lymphoepithelioma-like carcinoma (LELC) and T-cell non-Hodgkin lymphoma (NHL-T). The patient was a 61-year-old male presenting with a one-week history of low back pain. Positron emission tomography-computed tomography (PET-CT) revealed hypermetabolic masses in the anterior mediastinum, adjacent to right cardiophrenic angle, in the retroperitoneum, and adjacent to the left iliac vessels in the pelvis. The puncture biopsy of the mass adjacent to the cardiophrenic angle suggested LELC coexisting with NHL-T. The patient was treated with a combination regimen of a PD-1 inhibitor and platinum-based chemotherapy, but disease progression was observed. Subsequent biopsy of the pelvic mass confirmed the presence of NHL-T. The treatment regimen was then modified to include a PD-1 inhibitor, bortezomib, and ICE (ifosfamide, carboplatin, etoposide) chemotherapy. After two cycles, the response was assessed as partial remission. The patient remains on ongoing therapy. This case highlights diagnostic challenges and provides insights into the management of such rare collision tumors.
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2026-05-27 | Novel transposon BAFF CAR-T cells (LMY-920) for non-Hodgkin lymphoma (NHL).
2563 Background: CAR-T cells targeting CD19 using scFv-based CARs have been effective and approved to treat lymphoma. Response rates are high, but a significant number of patients fail to respond or relapse. This has been linked to T cell exhaustion, immune dysregulation, and/or epitope loss. To overcome this, we developed a CAR-T cell product expressing a BAFF-ligand (LMY-920). The CAR consists of truncated human BAFF on a 3rd generation CAR backbone with CD28, OX40, and CD3z intracellular signaling domains. The BAFF-ligand domain confers ability to bind the 3 BAFF receptors (BAFFR/BR3, TACI and BCMA). These are attractive tumor-associated antigens being variably expressed in all B-lineage malignancies such as B cell NHL, chronic lymphocytic leukemia (CLL), hairy cell leukemia and multiple myeloma (MM), and are important for B-cell survival, reducing the chance of antigen escape. Additionally, they are expressed on B-lineage cells involved in antibody-mediated autoimmune diseases. BAFF ligand interactions are lower affinity than scFv interactions, potentially reducing T-cell exhaustion. The novel TcBuster transposon system is used to improve manufacturing time, efficiency, cost, and safety. Methods: Patients with refractory B cell NHL are treated in this study (NCT05312801). Autologous LMY-920 CAR-T cells are manufactured, then patients receive 3 days of fludarabine (30 mg/m 2 /d) and cyclophosphamide (500 mg/m 2 /d) lymphodepletion. LMY-920 is administered intravenously in a 3+3 dose escalation design from 1-8 x 10 6 BAFF-CAR-T cells/kg. Response is assessed using the Lugano criteria. CAR-T expansion and biologic characteristics are assessed. Results: Five patients have been treated with 1-2 x 10 6 BAFF-CAR-T cells/kg in this study, 2 patients each with mantle cell lymphoma (MCL), diffuse large B cell lymphoma (DLBCL), and one with marginal zone lymphoma (MZL). Patients had received 2 – 6 prior lines of therapy and all were refractory. One patient experienced grade 1 CRS (fever), but no ICANS was reported. All patients experienced grade 3 or higher hematologic toxicity that recovered prior to day 28, and grade 1-2 fatigue. There have been no dose limiting toxicities and dose escalation continues. Responses included 2 complete responses (CR) (DLBCL), a partial response (MZL), a mixed response (MCL) and one stable disease (MCL). Of note, one of the DLBCL patients in CR had received prior axicabtagene ciloleucel (anti-CD19) CAR-T cells as well as anti-CD20 bispecific antibodies, with lymphoma cells resulting in CD19 and CD20 antigen loss. Conclusions: The successful use of a novel transposon-engineered BAFF ligand-based CAR-T cell product demonstrates the potential of a new direction in CAR-T cell development. Safety and efficacy were seen, including patients with prior CAR-T failure and epitope loss, as hypothesized. This product is also being evaluated in patients with CLL, MM and systemic lupus erythematosus. Clinical trial information: NCT05312801 .
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2026-05-08 | CAR-T cell therapy in non-Hodgkin lymphoma: a clinical trial landscape review
Background: Chimeric antigen receptor T cell (CAR-T) therapy has emerged as a transformative treatment modality for selected subtypes of non-Hodgkin lymphoma (NHL). While multiple CAR-T products have demonstrated remarkable clinical activity, the overall clinical development landscape remains heterogeneous, with substantial variation in trial design, target selection, geographic distribution, and endpoint prioritization. A comprehensive analysis of the global clinical trial landscape is essential to contextualize current progress and identify unmet needs in this rapidly evolving field. Methods: We conducted a systematic landscape analysis of CAR-T-related clinical trials for NHL using the Trialtrove database. Interventional trials registered up to December 18, 2025, were retrieved using predefined search criteria. Eligible studies were screened according to standardized inclusion and exclusion criteria. Key trial characteristics, including trial status, phase, geographic location, sponsor type, molecular targets, and reported clinical endpoints, were extracted and analyzed descriptively. Results: A total of 360 eligible clinical trials were included in the final analysis. The global CAR-T clinical trial landscape in NHL is characterized by rapid expansion and a predominant focus on early-phase development. Trial activity is highly concentrated in a limited number of countries, with academic institutions serving as the primary drivers of clinical investigation. CD19-directed CAR-T therapies dominate the current landscape, although emerging diversification toward alternative targets is evident. Reported study endpoints largely emphasize safety and short-term efficacy, whereas durable clinical outcomes remain less frequently assessed, reflecting the exploratory nature of most trials. Conclusion: CAR-T therapy development in NHL continues to advance rapidly, driven by academic innovation and expanding preclinical insights. However, persistent challenges related to antigen escape, treatment durability, and trial design remain. Future progress will require the integration of next-generation CAR engineering strategies, broader incorporation of long-term clinical endpoints, and alignment with evolving regulatory and policy frameworks to support sustainable clinical translation.
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