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

• Type of Material: Article
• Authors: Laurie H. Sehn, BC Cancer Centre for Lymphoid Cancer; Alex F. Herrera, City of Hope National Medical Center; Christopher Flowers, Emory University; Manali K. Kamdar, University of Colorado; Andrew McMillan, Nottingham University Hospitals; Mark Hertzberg, Prince Wales Hospital and University of NSW; Sarit Assouline, Jewish General Hospital; Tae Min Kim, Seoul National University Hospital; Won Seong Kim, Samsung Medical Center; Muhit Ozcan, Ankara University; Jamie Hirata, Genentech Inc.; Elicia Penuel, Genentech Inc.; Joseph N. Paulson, Genentech Inc.; Ji Cheng, F. Hoffman-La Roche; Grace Ku, Genentech Inc.; Matthew J. Matasar, Memorial Sloan Kettering Cancer Center
• Language: English
• Date: 2020-01-10
• Publisher: AMER SOC CLINICAL ONCOLOGY
• Publication Version: Final Published Version
• Copyright Statement: © 2019 by American Society of Clinical Oncology.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1200/JCO.19.00172
• Title of Journal or Parent Work: JOURNAL OF CLINICAL ONCOLOGY
• Volume: 38
• Issue: 2
• Start Page: 155
• End Page: +
• Keywords: BINDING; Science & Technology; Life Sciences & Biomedicine; ANTIBODY-DRUG CONJUGATE; LEUKEMIA; NON-HODGKIN-LYMPHOMA; Oncology; EXPRESSION; PLUS RITUXIMAB
• Research Categories: Health Sciences, Immunology; Health Sciences, Oncology

Abstract

PURPOSE 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. METHODS 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. RESULTS 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% v 17.5%; P = .026) and longer IRC-assessed PFS (median, 9.5 v 3.7 months; hazard ratio [HR], 0.36, 95% CI, 0.21 to 0.63; P, .001) and OS (median, 12.4 v 4.7 months; HR, 0.42; 95% CI, 0.24 to 0.75; P = .002; median followup, 22.3 months). Pola-BR patients had higher rates of grade 3-4 neutropenia (46.2% v 33.3%), anemia (28.2% v 17.9%), and thrombocytopenia (41% v 23.1%), but similar grade 3-4 infections (23.1% v 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. CONCLUSION 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.