Polatuzumab Vedotin As an Effective Salvage Therapy for Relapsed/Refractory Mantle Cell Lymphoma Resistantance to BTK and BCL Inhibitors

Background Novel immunotherapies and small molecular inhibitors including BTK inhibitors, BCL2 inhibtors and lenalidomide have substantially improved survival in relapsed/refractory MCL patients. Patient who resisted to BTK and BCL inhibitors, had more aggressive clinical features and poor prognosis. Previous study showed Polatuzumab vedotin (Pola) was effectiveness in the treatment of MCL. However, there are little previous reports on the efficacy of pola-combination therapy in the patients resistance to BTKi and BCL-2i.

Method This study is a prospective single center study, evaluating the efficacy of pola combined with obinutuzumab ± chemotherapy for 2-6 cycles. The primary endpoint was overall response after 2 cycles assessed by Lugano criteria. Safety analysis included all patients who received the treatment, irrespective of eligibility or duration of treatment.

Result The study included 9 patients with relapsed or refractory mantle-cell lymphoma. Patients were 44 to 73 years with a male-to-female ratio of 3:1. Clinical features were aggressive, 44.4% of patients were blastoid/pleomorphic histology, 77.7% of patients had ki-67 ≥50%, and 66.7% of patients had TP53 mutation. The lines of previous treatments were 4(2-9), and all patients were resistance to BTKi and BCL-2i. After 2 cycles, 55.6% patients obtained partial remission. Among of them, three patients received CD19-CART therapy and one patients (11.1%) got complete remission after 6 cycles. The most common grade 3-4 adverse events were neutropenia (in 2 [22.2%] of 9 patients), thrombocytopenia (in 2 [22.2%] of 9 patients), infections (in 1 [11.1%] patients).

ConclusionsOur results provide preliminary evidence that the combination of polatuzumab vedotin is an effective salvage therapy for high-risk relapsed/refractory mantle cell lymphoma resistantance to BTK and BCL inhibitors, especially as an optimum bridging choice before CART therapy. The result should be evaluated in a large-sample study.

No relevant conflicts of interest to declare.