PMID- 35015819
OWN - NLM
STAT- MEDLINE
DCOM- 20220426
LR  - 20220531
IS  - 2473-9537 (Electronic)
IS  - 2473-9529 (Print)
IS  - 2473-9529 (Linking)
VI  - 6
IP  - 4
DP  - 2022 Feb 22
TI  - Safety and activity of pembrolizumab in combination with rituximab in relapsed or 
      refractory follicular lymphoma.
PG  - 1143-1151
LID - 10.1182/bloodadvances.2021006240 [doi]
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 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.
CI  - (c) 2022 by The American Society of Hematology. Licensed under Creative Commons 
      Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), 
      permitting only noncommercial, nonderivative use with attribution. All other 
      rights reserved.
FAU - Nastoupil, Loretta J
AU  - Nastoupil LJ
AD  - Department of Lymphoma/Myeloma, San Diego, CA and.
FAU - Chin, Collin K
AU  - Chin CK
AD  - Department of Lymphoma/Myeloma, San Diego, CA and.
FAU - Westin, Jason R
AU  - Westin JR
AUID- ORCID: 0000-0002-1824-2337
AD  - Department of Lymphoma/Myeloma, San Diego, CA and.
FAU - Fowler, Nathan H
AU  - Fowler NH
AD  - Department of Lymphoma/Myeloma, San Diego, CA and.
FAU - Samaniego, Felipe
AU  - Samaniego F
AD  - Department of Lymphoma/Myeloma, San Diego, CA and.
FAU - Cheng, Xiaoyun
AU  - Cheng X
AD  - Department of Lymphoma/Myeloma, San Diego, CA and.
FAU - Ma, Man Chun John
AU  - Ma MCJ
AUID- ORCID: 0000-0002-2000-8144
AD  - Department of Lymphoma/Myeloma, San Diego, CA and.
FAU - Wang, Zhiqiang
AU  - Wang Z
AD  - Department of Lymphoma/Myeloma, San Diego, CA and.
FAU - Chu, Fuliang
AU  - Chu F
AD  - Department of Lymphoma/Myeloma, San Diego, CA and.
FAU - Dsouza, Ly
AU  - Dsouza L
AD  - Department of Lymphoma/Myeloma, San Diego, CA and.
FAU - Obi, Chizobam
AU  - Obi C
AD  - Department of Lymphoma/Myeloma, San Diego, CA and.
FAU - Mims, Jennifer
AU  - Mims J
AD  - Department of Lymphoma/Myeloma, San Diego, CA and.
FAU - Feng, Lei
AU  - Feng L
AD  - Department of Biostatistics, University of Texas MD Anderson Cancer Center, 
      Houston, TX.
FAU - Zhou, Shouhao
AU  - Zhou S
AUID- ORCID: 0000-0002-8124-5047
AD  - Department of Lymphoma/Myeloma, San Diego, CA and.
FAU - Green, Michael
AU  - Green M
AD  - Department of Lymphoma/Myeloma, San Diego, CA and.
FAU - Davis, Richard Eric
AU  - Davis RE
AD  - Department of Lymphoma/Myeloma, San Diego, CA and.
FAU - Neelapu, Sattva S
AU  - Neelapu SS
AUID- ORCID: 0000-0003-1045-4914
AD  - Department of Lymphoma/Myeloma, San Diego, CA and.
LA  - eng
SI  - ClinicalTrials.gov/NCT02446457
GR  - P30 CA016672/CA/NCI NIH HHS/United States
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Blood Adv
JT  - Blood advances
JID - 101698425
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 4F4X42SYQ6 (Rituximab)
RN  - DPT0O3T46P (pembrolizumab)
SB  - IM
MH  - Antibodies, Monoclonal, Humanized/therapeutic use
MH  - *Antineoplastic Combined Chemotherapy Protocols/adverse effects
MH  - Diarrhea/chemically induced
MH  - Humans
MH  - *Lymphoma, Follicular/drug therapy
MH  - Neoplasm Recurrence, Local/drug therapy
MH  - Rituximab/therapeutic use
PMC - PMC8864656
EDAT- 2022/01/12 06:00
MHDA- 2022/04/27 06:00
PMCR- 2022/02/14
CRDT- 2022/01/11 17:39
PHST- 2021/09/23 00:00 [received]
PHST- 2021/12/07 00:00 [accepted]
PHST- 2022/01/12 06:00 [pubmed]
PHST- 2022/04/27 06:00 [medline]
PHST- 2022/01/11 17:39 [entrez]
PHST- 2022/02/14 00:00 [pmc-release]
AID - 483433 [pii]
AID - 2022/ADV2021006240 [pii]
AID - 10.1182/bloodadvances.2021006240 [doi]
PST - ppublish
SO  - Blood Adv. 2022 Feb 22;6(4):1143-1151. doi: 10.1182/bloodadvances.2021006240.