Polatuzumab vedotin in combination with bendamustine and rituximab in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: Interim analysis
Authors: O. Smykova, V. Markelov, K. Lepik, L. Fedorova, E. Borzenkova, E. Kondakova, L. Stelmakh, V. Baykov, I. Moiseev, N. Mikhailova, A. Kulagin
Journal: HemaSphere (2021)

Background: The outcomes of relapsed or refractory B-cell non-Hodgkin lymphoma (r/r B-NHL) are very dismal with no standard of therapy. Relapsed or refractory B-NHL are heterogeneous group of lymphoproliferative malignancies with histological, cytogenetic and molecular differences, but all of them have a B-cell receptor. CD79b is a B-cell receptor component and the antibody-drug conjugate polatuzumab vedotin is an anti-CD79b antibody linked to antimitotic agent - monomethyl auristatin E. Polatuzumab vedotin in combination with bendamustine and rituximab (Pola-BR) demonstrated efficacy in patients with r/r B-NHL. Aims: To evaluate the safety and effectiveness of Pola-BR in patients with r/r B-NHL in real clinical practice. Methods: This is interim analysisof single-center prospective study evaluates efficacy and safety of Pola-BR for treatment patients with aggressive r/r B-NHL. All patients received bendamustine 90 mg/m2 on days 1 and 2, rituximab 375 mg/m2 on day 1 and polatuzumab vedotin 1,8 mg/kg on day 1 of each 21-day cycle. The PET-CT scan was performed before treatment initiation and after 2, 4, 6 cycles of Pola-BR. The responses were evaluated using Lugano 2014 criteria. Toxicity was graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v 4.03. Results: Total of 26 patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) (n=18), primary mediastinal B-cell lymphoma (PMBCL) (n=7) and gray zone lymphoma (GZL) (n=1) were included. All diagnoses were histologically confirmed. Median age was 43 years (range 20-68). Most of the patients 73% (n=19) had primary chemoresistant disease. The median number of prior therapy lines was 3 (range 2-10). Five patients underwent autologous stem cell transplantation and four patients received anti-CD19 CAR-T cell therapy. At the start of Pola-BR treatment stage III-IV disease had 73% (n=19) patients and 27% (n=7) of patients had bulky disease. Median number of Pola-BR cycles was 4 (range 2-6). Nine patients (35%) completed 6 cycles of Pola-BR. Eight patients (31%) interruptedPola-BR treatment due to disease progression. The overall response rate (ORR) in the group was 61% (n=16) with 46% (n=12) of complete responses (CR) and 15% (n=4) of partial responses (PR). Two patients (8%) had stabilization of the disease as best response. The ORR in patients with DLBCL was 57% (CR 44%), in patients with PMBCL ORR was 57% (CR 43%) and one patient with GZL achieved CR. The ORR in patients with bulky disease was 14% (CR 14%) and ORR 79% (CR 58%) in patients without bulky disease. In patients with relapsed disease ORR was 86% (CR 57%) and in patients with primary chemoresistant disease ORR was 53% (CR 42%). Two patients (50%) with primary CAR-T cell therapy achieved CR. With a median follow up time 6,8 (range 2-12) month overall survival and progression free survival were 71% and 57%, respectively. During Pola-BR treatment grade 3-4 anemia, neutropenia, and thrombocytopenia developed in 19% (n=5), 42% (n=11) and 12% (n=3) patients, respectively. Other adverse events included febrile neutropenia 8% (n=2) and maculopapular rash 8% (n=2). None of the patients had peripheral neuropathy. Two patients with PR died due to Covid-19 infection. Summary/Conclusion: Our real-life data confirms that Pola-BR has an acceptable toxicity profile and it is promising method of immunochemotherapy for patients with r/r B-NHL.