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

Mantle cell lymphoma (MCL) remains an incurable B-cell malignancy despite major advances in its therapeutic management. While Bruton tyrosine kinase inhibitors (BTKi) and, more recently, CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy have significantly improved outcomes in relapsed or refractory MCL, relapse after CAR-T therapy is associated with a dismal prognosis and represents a major therapeutic challenge. Here, we report the case of a 43-year-old male diagnosed with stage IV common-type MCL, who achieved long-term complete remission (CR) after treatment with polatuzumab vedotin, rituximab, and bendamustine (Pola-R-Benda) following relapse after CAR-T therapy. The patient had previously received standard first-line immunochemotherapy (R-CHOP alternating with R-DHAP) and autologous stem-cell transplantation, resulting in durable CR, followed by ibrutinib at first relapse in 2017 with sustained remission until 2021. Eleven months after CAR-T therapy with brexucabtagene autoleucel, the patient experienced systemic relapse. Enrollment into a Pola-R-Benda clinical protocol resulted in complete metabolic remission after three cycles, confirmed by positron emission tomography/computer tomography. Treatment was well tolerated except for mild grade 2 diarrhea. The patient remains in ongoing CR >20 months after initiation of Pola-R-Benda. To our knowledge, this is among the first reports of long-term remission with Pola-R-Benda following CAR-T failure in MCL, suggesting that antibody-drug conjugate-based therapy may represent an effective salvage option in this highly refractory clinical setting.