How an ADC Worked After CAR T-Cell Relapse in MCL

As novel therapies move into earlier lines of care in blood cancers, a new question has emerged for clinicians: what comes next when patients relapse after chimeric antigen receptor (CAR) T-cell therapy?

A recent case report by Sunder-Plassmann et al explores this question in the context of a 43-year-old man with mantle cell lymphoma (MCL) who achieved a durable complete remission with an antibody-drug conjugate (ADC) regimen after a relapse following CAR T-cell therapy.¹ Historically, such a relapse has been bad news.

“Patients relapsing after CAR T-cell therapy…face a dismal prognosis, and the median PFS and the OS have been reported at 2.5 and 5.4 months, respectively,” the authors wrote, citing a 2025 analysis in Blood Advances.²

The patient in the case report, which appeared in Therapeutic Advances in Medical Oncology, was diagnosed with stage IV common-type MCL in 2013 and treated according to standard of care: alternating chemo-immunotherapy regimens R-CHOP (rituximab, cyclophosphamide, hydroxydaunorubicin [doxorubicin], oncovin [vincristine], and prednisone [prednisolone]/R-DHAP (rituximab, dexamethasone, high-dose Ara-C [cytarabine], and Pisplatin [cisplatin]) followed by autologous stem-cell transplant, achieving complete remission. He relapsed in 2017 and was treated with the Bruton tyrosine kinase (BTK) inhibitor ibrutinib (Imbruvica; Janssen), again reaching complete remission, which he sustained until the drug was stopped in 2021 for compliance reasons, rather than progression.

In February 2022, the patient experienced disease recurrence, prompting treatment with brexucabtagene autoleucel (brexu-cel/Tecartus; Gilead), a CD19-directed CAR T-cell therapy. The patient tolerated it well, the authors report; management of cytokine release syndrome required 2 doses of tocilizumab, and he achieved complete remission on PET/CT.

However, 11 months later he relapsed systemically with pulmonary and lymph node involvement. A biopsy confirmed classical MCL with retained CD19 and CD79a expression, which the authors said pointed against antigen loss as the mechanism of CAR-T failure and supported CD79b as a viable therapeutic target.

At this point, the patient was enrolled in an academic trial of polatuzumab vedotin (Polivy; Genentech), an anti-CD79b ADC, combined with rituximab and bendamustine (BR)—a regimen borrowed from diffuse large B-cell lymphoma, where it improved PFS and OS over BR alone in the GO29365 trial.³ After just 3 cycles, the patient achieved complete metabolic remission on PET/CT. Treatment was well tolerated, with only mild grade 2 diarrhea and no cytopenias, infections, or worsening neuropathy. After the fifth cycle, he developed an acute coronary event that required stenting. This was attributed to underlying severe 3-vessel coronary disease and a substantial smoking history rather than a direct drug effect, although the authors note ADCs including polatuzumab have been associated with cardiac safety signals in pharmacovigilance data. Treatment was discontinued at 5 cycles (of 6 planned) due to this event, but the patient has remained in complete remission for more than 20 months since starting Pola-BR, with no relapse as of late 2025.

The authors describe this case as one of the first reports of long-term remission with an ADC-based regimen following CAR-T failure in MCL, a population with no established salvage standard. They discuss possible contributors to the favorable outcome: preserved CD79b targetability, a relatively late relapse after CAR T-cell treatment (11 months, associated with better prognosis than earlier relapses per DESCAR-T registry data), and a structured early intervention. They also raise the possibility of using Pola-BR as a bridging strategy before CAR T-cell infusion, while flagging that bendamustine can impair T-cell fitness and CAR T expansion, making the optimal sequencing uncertain.

The case report explicitly acknowledges its limitations as a single-patient observation with no biomarker to predict which patients would benefit, and notes that second- and third-generation BTK inhibitors—acalabrutinib (Calquence; AstraZeneca) zanubrutinib (Brukinsa; BeOne Medicines), and pirtobrutinib (Jaypirca; Eli Lilly)—may reshape treatment algorithms in the future.

The authors conclude that Pola-BR is a reasonable individualized salvage option in this high-need setting pending prospective data and encourage enrolling post-CAR-T MCL patients in trials of ADC-based strategies.

“Until prospective data become available, [Pola-BR] may be considered a rational individualized salvage strategy, particularly for younger and fit patients, but prospective evidence is required before definitive conclusions can be drawn,” they wrote. “Our results furthermore encourage inclusion of post-CAR-T MCL patients in salvage trials of [Pola-BR] or other novel strategies.”¹

References

1. Sunder-Plassman 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. 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
3. 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 extentsion (Ext) study. Blood 2022; 140 (suppl 1): 9464–9467. doi: https://doi.org/10.1182/blood-2022-157679