A case report describes a prolonged remission in a patient with mantle cell lymphoma (MCL) who relapsed after CD19-directed chimeric antigen receptor (CAR) T-cell therapy and was subsequently treated with polatuzumab vedotin (Polivy®; Genentech/Roche) plus bendamustine (Treanda®; Teva/Cephalon) and rituximab (Rituxan®; Genentech/Biogen). Polatuzumab vedotin is approved for diffuse large B-cell lymphoma (DLBCL), but not for MCL; its use in this post-CAR T-cell setting remains investigational.
This article was first published in ADC Review | J. Antibody-drug Conjugates on August 31, 2026.
Summary of Key Takeaways
- Relapse after CD19-directed CAR T-cell therapy in mantle cell lymphoma (MCL) is associated with poor outcomes. Real-world registry data report median progression-free survival of approximately 2.5 months and overall survival of approximately 5.4 months after relapse.
- In this case, a biopsy obtained at relapse showed persistent expression of CD19 and CD79a. The findings did not indicate CD19 antigen loss and identified CD79b as an alternative therapeutic target.
- Polatuzumab vedotin combined with bendamustine and rituximab (Pola-BR), a regimen developed for diffuse large B-cell lymphoma (DLBCL), produced complete metabolic remission after three cycles. The remission persisted for more than 20 months after treatment was stopped following cycle 5.
- The regimen was generally well tolerated, with grade 2 diarrhea reported. An acute coronary event after cycle 5 was attributed by the treating investigators to severe pre-existing three-vessel coronary artery disease and a substantial smoking history rather than to polatuzumab vedotin.
- The appropriate sequencing of ADC-based therapy and CAR T-cell therapy remains unresolved. Bendamustine can affect T-cell fitness, raising a concern when administered before leukapheresis or CAR T-cell infusion.
A Familiar Treatment Course, Followed by CAR T-Cell Relapse
Mantle cell lymphoma has benefited from several targeted treatment approaches, including Bruton tyrosine kinase (BTK) inhibitors and CD19-directed chimeric antigen receptor (CAR) T-cell therapy. Despite these advances, MCL remains incurable, and relapse following CAR T-cell therapy is associated with particularly poor outcomes.
A case report published in Therapeutic Advances in Medical Oncology describes a patient who achieved a prolonged remission after relapse following CD19-directed CAR T-cell therapy, following treatment with polatuzumab vedotin, bendamustine, and rituximab. [1]
The patient was a 43-year-old man diagnosed with stage IV common-type MCL in 2013. Initial treatment consisted of alternating R-CHOP and R-DHAP chemotherapy followed by autologous stem-cell transplantation. He achieved a complete remission. The lymphoma relapsed in 2017, and treatment was changed to the BTK inhibitor ibrutinib (Imbruvica; Janssen). He again achieved complete remission. According to the case report, ibrutinib was discontinued in 2021 for adherence-related reasons rather than disease progression.*
The lymphoma subsequently recurred in February 2022. The patient received brexucabtagene autoleucel (brexu-cel; Tecartus®, Gilead Sciences), a CD19-directed CAR T-cell therapy approved by the FDA for relapsed or refractory MCL, based on the Phase 2 ZUMA-2 study. [2] He experienced cytokine release syndrome requiring two doses of tocilizumab but otherwise tolerated CAR T-cell therapy well and achieved a complete remission on PET/CT.
The response lasted 11 months.
The patient then developed systemic relapse involving the lungs and lymph nodes. Real-world data from the Center for International Blood and Marrow Transplant Research (CIBMTR) indicate that outcomes after relapse following CAR T-cell therapy in MCL are poor. The case report cites a median progression-free survival of approximately 2.5 months and a median overall survival of approximately 5.4 months in this population. [3]
CD79b Provided a Different Therapeutic Target
A biopsy obtained at relapse showed classical MCL with retained expression of CD19 and CD79a.
The retained CD19 expression was clinically relevant because loss of the CD19 target is one mechanism associated with resistance to CD19-directed CAR T-cell therapy. In this patient, the biopsy did not demonstrate loss of CD19 antigen. The biopsy also confirmed CD79a expression, while CD79b was an alternative target for antibody-drug conjugate therapy.
CD79b is a component of the B-cell receptor complex and is expressed across many mature B-cell malignancies. Polatuzumab vedotin (Polivy; Genentech/Roche) is a CD79b-directed ADC consisting of a humanized anti-CD79b monoclonal antibody linked to the microtubule inhibitor monomethyl auristatin E (MMAE) through a protease-cleavable linker. [4] After binding CD79b, the ADC is internalized by the malignant B cell. Lysosomal enzymes cleave the linker, releasing MMAE intracellularly. MMAE disrupts microtubule function, resulting in cell-cycle arrest and apoptosis.
Polatuzumab vedotin is not approved for MCL. Its approved indications are in DLBCL. The FDA initially granted accelerated approval in 2019 for polatuzumab vedotin in combination with bendamustine and rituximab for patients with relapsed or refractory DLBCL after at least two prior therapies. The drug was subsequently approved in combination with R-CHP for previously untreated DLBCL with an International Prognostic Index score of 2 or higher. [5][6]
In the reported MCL case, Pola-BR was administered as investigational therapy through an academic clinical trial.
Applying a DLBCL Regimen in MCL
The clinical evidence supporting Pola-BR comes primarily from DLBCL rather than MCL.
In the randomized portion of the Phase 1b/2 GO29365 study, Pola-BR produced a complete response rate of 42.5%, compared with 17.5% with bendamustine plus rituximab (BR) alone. Median progression-free survival was 9.2 months with Pola-BR versus 3.7 months with BR, while median overall survival was 12.4 months versus 4.5 months, respectively. [6]
The subsequent single-arm extension cohort produced a similar complete response rate of approximately 40%. Treatment-related toxicity was substantial in the GO29365 population. Grade 3–4 adverse events occurred in approximately 78%-87% of patients across the study cohorts, with neutropenia and thrombocytopenia among the most common. Peripheral neuropathy was also reported and generally improved over time. These data provide clinical support for the activity of Pola-BR in DLBCL. They do not establish its efficacy in MCL, nor do they address treatment after CAR T-cell failure. The use of Pola-BR in the reported patient therefore represented an extrapolation based on the presence of the CD79b target rather than evidence from a disease-matched clinical trial.
Complete Metabolic Remission After CAR T-Cell Failure
Following systemic relapse, the patient enrolled in an academic clinical trial evaluating polatuzumab vedotin with bendamustine and rituximab. A complete metabolic remission was documented on PET/CT after three cycles. Treatment was generally well tolerated. Grade 2 diarrhea was the principal reported toxicity. The case report did not describe cytopenias, infections, or worsening peripheral neuropathy during treatment.
After the fifth of six planned cycles, the patient developed an acute coronary event that required coronary stenting. The investigators attributed the event to severe pre-existing three-vessel coronary artery disease and a substantial smoking history rather than to a direct effect of polatuzumab vedotin.
The authors nevertheless noted that pharmacovigilance data have identified cardiac safety signals with polatuzumab vedotin and other ADCs. The reported case does not establish a causal relationship between the ADC and the coronary event. Treatment was discontinued after five cycles. More than 20 months after treatment, as of late 2025, the patient remained in complete remission without additional therapy. The authors describe the case as one of the first reports of a long-term remission achieved with an ADC-based regimen following CAR T-cell failure in MCL, a setting for which no established salvage standard exists.
Factors Identified by the Authors
The case report identifies several factors that may have contributed to the observed response.
- First, the relapsed lymphoma retained CD79b expression, providing the target for polatuzumab vedotin.
- Second, the patient’s relapse occurred 11 months after CAR T-cell infusion. The authors cite CIBMTR-derived data indicating that patients who relapse later after CAR T-cell therapy have better outcomes than those who relapse earlier.[3]
- Third, treatment was initiated through an academic clinical trial rather than after multiple sequential salvage regimens.
The authors also discuss the potential use of Pola-BR as a bridge to CAR T-cell therapy. They present this as a hypothesis for future investigation rather than as a treatment recommendation.
The issue of treatment sequencing is particularly important because bendamustine can impair T-cell fitness. Administering bendamustine close to leukapheresis or CAR T-cell infusion could potentially affect the ability to manufacture or expand CAR T cells. The available case report does not establish the optimal sequence for ADC-based treatment and cellular therapy.
What the Case Does — and Does Not — Show
The principal limitation is straightforward: this is a single-patient case report. The response cannot establish how frequently patients with MCL will respond to Pola-BR after CAR T-cell failure, nor does it identify a biomarker that can predict response. The retained expression of CD79b provides a biologically relevant target, but the case does not establish CD79b expression as a validated predictive biomarker for polatuzumab vedotin in MCL.
The treatment landscape for relapsed or refractory MCL is also changing. Second- and third-generation BTK inhibitors, including acalabrutinib (Calquence; AstraZeneca), zanubrutinib (Brukinsa; BeOne Medicines), and pirtobrutinib (Jaypirca; Eli Lilly), have expanded therapeutic options and may influence the role of other salvage approaches. [1]
Evidence regarding Pola-BR and subsequent cellular therapy comes primarily from DLBCL. A retrospective single-institution analysis of Japanese patients with relapsed or refractory DLBCL evaluated Pola-BR, including patients treated with the intent to proceed to CAR T-cell therapy. The overall response rate was 69.0%, and the complete response rate was 27.6%. Most patients in the CAR T-cell–intent cohort subsequently proceeded to CAR T-cell manufacturing, including several who received bendamustine-containing Pola-BR before leukapheresis. [7]
These findings are not specific to MCL or to patients who have relapsed after CAR T-cell therapy. They also do not resolve the question of how exposure to bendamustine affects T-cell function. They do, however, provide clinical experience showing that bendamustine-containing Pola-BR did not universally prevent subsequent CAR T-cell manufacturing in that DLBCL population.
The Authors’ Conclusion
The authors present Pola-BR as an individualized treatment option in a setting with limited established therapy and recommend further investigation of ADC-based salvage strategies in patients with MCL who relapse after CAR T-cell therapy.
The case does not establish Pola-BR as a standard of care for relapsed MCL after CAR T-cell therapy. Its significance is more limited and more specific: a patient with MCL who relapsed after CD19-directed CAR T-cell therapy achieved a complete metabolic remission with a CD79b-directed ADC regimen, and that remission persisted for more than 20 months after treatment was discontinued.
Prospective studies will be required to determine whether this response can be reproduced and whether CD79b-directed therapy has a defined role in the post-CAR T-cell treatment of MCL.
Note: * In April 2023, Janssen and Pharmacyclics voluntarily withdrew ibrutinib’s accelerated approvals specifically for MCL after one prior therapy, and for marginal zone lymphoma, after confirmatory phase 3 trials did not confirm sufficient clinical benefit in those indications; ibrutinib remains FDA-approved and widely prescribed for chronic lymphocytic leukemia/small lymphocytic lymphoma, Waldenström macroglobulinemia, and chronic graft-versus-host disease.[8,9] That indication withdrawal postdated this patient’s ibrutinib course and is noted here only for regulatory context relevant to today’s treatment algorithms.
Highlights of Prescribing Information
Polatuzumab vedotin (Polivy®; Genentech/Roche)[Prescribing Information]
Bendamustine (Treanda®; Teva/Cephalon) [Prescribing Information]
Rituximab (Rituxan®; Genentech/Biogen)[Prescribing Information]
Brexucabtagene autoleucel (brexu-cel; Tecartus®, Gilead Sciences)[Prescribing Information]
Ibrutinib (Imbruvica®; Pharmacyclics/Janssen Biotech)[Prescribing Information]
References
[1] Sunder-Plassmann V, Kiesewetter B, Raderer M. Long-term complete remission following treatment with polatuzumab vedotin, rituximab, and bendamustine in a patient with mantle cell lymphoma relapsing after CAR T-cell therapy: a case report. Ther Adv Med Oncol. 2026;18:1-8. doi:10.1177/17588359261472319
[2] U.S. Food and Drug Administration / Gilead Sciences. FDA grants full approval of brexucabtagene autoleucel (Tecartus) for adult patients with relapsed or refractory mantle cell lymphoma, based on the Phase 2 ZUMA-2 trial. April 2026.
[3] Ahmed N, Thiruvengadam SK, Hamadani M, et al. Real-world outcomes of brexucabtagene autoleucel for relapsed or refractory mantle cell lymphoma: a CIBMTR analysis. Blood Adv. 2025;9(20):5382-5396. doi:10.1182/bloodadvances.2024015014
[4] POLIVY (polatuzumab vedotin-piiq) full prescribing information. Genentech, Inc. Initial U.S. approval 2019.
[5] Sehn LH, Kamdar M, Herrera AF, et al. Polatuzumab vedotin in combination with bendamustine and rituximab for relapsed/refractory diffuse large B-cell lymphoma. J Clin Oncol. 2020.
[6] Sehn LH, Hertzberg M, Opat S, et al. Polatuzumab vedotin plus bendamustine and rituximab in relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL): final results of a phase Ib/II randomized study and single-arm extension study. Blood. 2022;140(suppl 1):9464-9467. doi:10.1182/blood-2022-157679
[7] Morita Y, Yagi Y, Kanemasa Y, et al. Polatuzumab vedotin, bendamustine, and rituximab in patients with relapsed/refractory diffuse large B-cell lymphoma, including outcome as bridging treatment to CAR T-cell therapy or allogeneic hematopoietic stem cell transplant. [Article in Japanese]. 2023. doi:10.11406/rinketsu.64.586
[8] Johnson & Johnson. Update on IMBRUVICA (ibrutinib) U.S. accelerated approvals for mantle cell lymphoma and marginal zone lymphoma indications. Press release. April 2023.
This article is intended for healthcare professional audiences and summarizes published case-report and clinical trial data. It is not a treatment recommendation. Polatuzumab vedotin is not FDA-approved for mantle cell lymphoma; its use in the case described was investigational.
Featured image © 2026 CH/JCO Used with permission.
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