Safety and Activity of Pembrolizumab in Combination With Rituximab in Relapsed or Refractory Follicular Lymphoma

Authors

Loretta J Nastoupil
Collin K Chin
Jason R Westin
Nathan H Fowler
Felipe Samaniego
Xiaoyun Cheng
Man Chun John Ma
Zhiqiang Wang
Fuliang Chu
Ly Dsouza
Chizobam Obi
Jennifer Mims
Lei Feng
Shouhao Zhou
Michael Green
Richard Eric Davis
Sattva S Neelapu

Publication Date

2-22-2022

Journal

Blood Advances

Abstract

PD-1 blockade enhances the function of antitumor T cells and antibody-dependent, cell-mediated cytotoxicity (ADCC) of NK cells. In a single-center, open-label, phase 2 trial, we tested the combination of pembrolizumab, an anti-PD-1 monoclonal antibody, and rituximab, an anti-CD20 monoclonal antibody that induces ADCC, in 30 patients with follicular lymphoma (FL) with rituximab-sensitive disease who had relapsed after ≥1 prior therapy. Pembrolizumab was administered at 200 mg IV every 3 weeks for up to 16 cycles, and rituximab was given at 375 mg/m2 IV weekly for 4 weeks in cycle 1 only. The most common grade 3/4 adverse events (AEs) were liver enzyme abnormalities (3%), diarrhea (3%), nausea (3%), aseptic meningitis (3%), and pancreatitis (3%). Low-grade immune-related AEs were reported in 80% of patients, including diarrhea (43%), liver enzyme abnormalities (33%), thyroid dysfunction (27%), and rash (23%). Grade 3 or 4 immune-related AEs occurred in 13% of the patients. Treatment-related AEs led to discontinuation in 6 (20%) patients. The overall response rate (primary end point) was 67%, and the complete response (CR) rate was 50%. Median progression-free survival (PFS) was 12.6 months (95% confidence interval, 8.2-27.6), the 3-year overall survival rate was 97%, and 23% of patients were in remission at a median follow-up of 35 months. The presence of a high CD8+ T-effector score at baseline in the tumor was associated with induction of a CR and improved PFS. In this single-arm, phase 2 study, the combination of pembrolizumab and rituximab demonstrates favorable efficacy and safety profile in relapsed FL. This trial is registered at www.clinicaltrials.gov as #NCT02446457.

Keywords

Antibodies, Monoclonal, Humanized, Antineoplastic Combined Chemotherapy Protocols, Diarrhea, Humans, Lymphoma, Follicular, Neoplasm Recurrence, Local, Rituximab

DOI

10.1182/bloodadvances.2021006240

PMID

35015819

PMCID

PMC8864656

PubMedCentral® Posted Date

2-14-2022

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes