TY - JOUR
T1 - Safety and activity of pembrolizumab in combination with rituximab in relapsed or refractory follicular lymphoma
AU - Nastoupil, Loretta J.
AU - Chin, Collin K.
AU - Westin, Jason R.
AU - Fowler, Nathan H.
AU - Samaniego, Felipe
AU - Cheng, Xiaoyun
AU - Ma, Man Chun John
AU - Wang, Zhiqiang
AU - Chu, Fuliang
AU - Dsouza, Ly
AU - Obi, Chizobam
AU - Mims, Jennifer
AU - Feng, Lei
AU - Zhou, Shouhao
AU - Green, Michael
AU - Davis, Richard Eric
AU - Neelapu, Sattva S.
N1 - Funding Information:
This work is supported by grants from Merck, a Leukemia and Lymphoma Society Quest for Cure grant (P-QFC-3068-14) (S.S.N.), generous philanthropic contributions to the University of Texas Anderson Moon Shots Program, and The University of Texas Anderson Cancer Center Support from National Institutes of Health, National Cancer Institute grant P30CA016672.
Funding Information:
Funding support for this article was provided by the The University of Texas MD Anderson Cancer Center Support Grant from National Institutes of Health (P30 CA016672)
Publisher Copyright:
© 2022 by The American Society of Hematology.
PY - 2022/2/22
Y1 - 2022/2/22
N2 - 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 CD81 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.
AB - 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 CD81 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.
UR - http://www.scopus.com/inward/record.url?scp=85125353007&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85125353007&partnerID=8YFLogxK
U2 - 10.1182/bloodadvances.2021006240
DO - 10.1182/bloodadvances.2021006240
M3 - Article
C2 - 35015819
AN - SCOPUS:85125353007
SN - 2473-9529
VL - 6
SP - 1143
EP - 1151
JO - Blood Advances
JF - Blood Advances
IS - 4
ER -