Polatuzumab Vedotin in Relapsed or Refractory Diffuse Large B-Cell Lymphoma.

Abstract

Patients with transplantation-ineligible relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) fare poorly, with limited treatment options. The antibody-drug conjugate polatuzumab vedotin targets CD79b, a B-cell receptor component. Safety and efficacy of polatuzumab vedotin with bendamustine and obinutuzumab (pola-BG) was evaluated in a single-arm cohort. Polatuzumab vedotin combined with bendamustine and rituximab (pola-BR) was compared with bendamustine and rituximab (BR) in a randomly assigned cohort of patients with transplantation-ineligible R/R DLBCL (primary end point: independent review committee [IRC] assessed complete response [CR] rate at the end of treatment). Duration of response, progression-free survival (PFS), and overall survival (OS) were analyzed using Kaplan-Meier and Cox regression methods. Pola-BG and pola-BR had a tolerable safety profile. The phase Ib/II pola-BG cohort (n = 27) had a CR rate of 29.6% and a median OS of 10.8 months (median follow-up, 27.0 months). In the randomly assigned cohort (n = 80; 40 per arm), pola-BR patients had a significantly higher IRC-assessed CR rate (40.0% <i>v</i> 17.5%; <i>P</i> = .026) and longer IRC-assessed PFS (median, 9.5 <i>v</i> 3.7 months; hazard ratio [HR], 0.36, 95% CI, 0.21 to 0.63; <i>P</i> < .001) and OS (median, 12.4 <i>v</i> 4.7 months; HR, 0.42; 95% CI, 0.24 to 0.75; <i>P</i> = .002; median follow-up, 22.3 months). Pola-BR patients had higher rates of grade 3-4 neutropenia (46.2% <i>v</i> 33.3%), anemia (28.2% <i>v</i> 17.9%), and thrombocytopenia (41% <i>v</i> 23.1%), but similar grade 3-4 infections (23.1% <i>v</i> 20.5%), versus the BR group. Peripheral neuropathy associated with polatuzumab vedotin (43.6% of patients) was grade 1-2 and resolved in most patients. Polatuzumab vedotin combined with BR resulted in a significantly higher CR rate and reduced the risk of death by 58% compared with BR in patients with transplantation-ineligible R/R DLBCL.