Polatuzumab vedotin in relapsed or refractory diffuse large B-cell lymphoma Journal Article


Authors: Sehn, L. H.; Herrera, A. F.; Flowers, C. R.; Kamdar, M. K.; McMillan, A.; Hertzberg, M.; Assouline, S.; Kim, T. M.; Kim, W. S.; Ozcan, M.; Hirata, J.; Penuel, E.; Paulson, J. N.; Cheng, J.; Ku, G.; Matasar, M. J.
Article Title: Polatuzumab vedotin in relapsed or refractory diffuse large B-cell lymphoma
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. © 2019 by American Society of Clinical Oncology.
Keywords: adult; cancer survival; controlled study; treatment response; aged; major clinical study; overall survival; constipation; drug tolerability; fatigue; neutropenia; paresthesia; cancer recurrence; diarrhea; drug efficacy; drug safety; conference paper; rituximab; follow up; progression free survival; infection; multiple cycle treatment; phase 2 clinical trial; sensory neuropathy; anemia; nausea; randomized controlled trial; thrombocytopenia; peripheral neuropathy; cohort analysis; bendamustine; autologous stem cell transplantation; tumor marker; febrile neutropenia; fever; lymphocytopenia; germinal center; cancer regression; multicenter study; recurrent disease; open study; phase 1 clinical trial; metabolic disorder; follicular lymphoma; hypesthesia; motor neuropathy; international prognostic index; decreased appetite; clinical outcome; diffuse large b cell lymphoma; nutritional disorder; human; male; female; priority journal; median survival time; obinutuzumab; polatuzumab vedotin; cd79b antigen; decreased vibratory sense; refractory diffuse large b cell lymphoma
Journal Title: Journal of Clinical Oncology
Volume: 38
Issue: 2
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2020-01-10
Start Page: 155
End Page: 165
Language: English
DOI: 10.1200/jco.19.00172
PUBMED: 31693429
PROVIDER: scopus
PMCID: PMC7032881
DOI/URL:
Notes: Source: Scopus
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors
  1. Matthew J Matasar
    290 Matasar