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 - 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.
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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 -