Polatuzumab vedotin as a salvage and bridging treatment in relapsed or refractory large B-cell lymphomas

Abstract

The antibody-drug conjugate polatuzumab vedotin (pola) has recently been approved in combination with bendamustine and rituximab (pola-BR) for patients with refractory or relapsed (r/r) large B-cell lymphoma (LBCL). To investigate the efficacy of pola-BR in a real-world setting, we retrospectively analyzed 105 patients with LBCL who were treated in 26 German centers under the national compassionate use program. Fifty-four patients received pola as a salvage treatment and 51 patients were treated with pola with the intention to bridge to chimeric antigen receptor (CAR) T-cell therapy (n = 41) or allogeneic hematopoietic cell transplantation (n = 10). Notably, patients in the salvage and bridging cohort had received a median of 3 prior treatment lines. In the salvage cohort, the best overall response rate was 48.1%. The 6-month progression-free survival and overall survival (OS) was 27.7% and 49.6%, respectively. In the bridging cohort, 51.2% of patients could be successfully bridged with pola to the intended CAR T-cell therapy. The combination of pola bridging and successful CAR T-cell therapy resulted in a 6-month OS of 77.9% calculated from pola initiation. Pola vedotin-rituximab without a chemotherapy backbone demonstrated encouraging overall response rates up to 40%, highlighting both an appropriate alternative for patients unsuitable for chemotherapy and a new treatment option for bridging before leukapheresis in patients intended for CAR T-cell therapy. Furthermore, 7 of 12 patients with previous failure of CAR T-cell therapy responded to a pola-containing regimen. These findings suggest that pola may serve as effective salvage and bridging treatment of r/r LBCL patients.

Graphical abstract

Figure 1.

Outcome of patients in the salvage cohort. (A-B) Progression-free survival and overall survival of the salvage cohort. (C-D) Progression-free survival and overall survival stratified by the number of prior systemic treatment lines. Survival times were calculated from the initiation of polatuzumab vedotin (pola) treatment.

Figure 2.

Multivariate analysis of risk factors for inferior outcome. Forest plots for (A) progression-free survival and (B) overall survival. Pola(-R)-chemo, polatuzumab vedotin and chemotherapy ± rituximab.

Figure 3.

Outcome of patients in the bridging cohort. (A) Actual treatment of patients intended for CAR T-cell therapy and (B) overall survival of patients who received the intended CAR T-cell therapy after polatuzumab vedotin (pola) bridging. (C-D) Intent-to-treat-analysis with progression-free survival and overall survival of complete bridging cohort intended for CAR T-cell therapy. Survival times were calculated from the initiation of pola treatment. For the estimation of progression-free survival, data were only assessed in the efficacy-evaluable population. Three patients had no response evaluation and were excluded from the progression-free survival estimation.