TY - JOUR
T1 - Pembrolizumab for myelodysplastic syndromes after failure of hypomethylating agents in the phase 1b KEYNOTE-013 study
AU - Garcia-Manero, Guillermo
AU - Ribrag, Vincent
AU - Zhang, Yayan
AU - Farooqui, Mohammed
AU - Marinello, Patricia
AU - Smith, B. Douglas
N1 - Funding Information:
The authors thank the patients and their families and caregivers and all primary investigators and their site personnel. The authors also thank Brooke Burton (employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA) for clinical study support and Luana Atherly-Henderson, PhD, CMPP (employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA) for medical writing and/or editorial support. Additional medical writing and/or editorial assistance was provided by Dominic Singson, MD, and Matthew Grzywacz, PhD, of ApotheCom (Yardley, PA, USA). This assistance was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Funding Information:
G.G.M. has received funding for the current manuscript from the NIH Cancer Center; has received research funding from Amphivena, Helsinn, Novartis, AbbVie, Bristol Myers Squibb, Astex, Onconova, H3 Biomedicine, Merck & Co., Inc., Curis, Janssen, Genentech, Forty Seven, and Aprea; and has been a consultant for Bristol Myers Squibb, Astex, Helsinn, and Genentech. VR has received honoraria from AZD and Roche; has received research funding from GlaxoSmithKline, Argen-X, and Astex; and has participated on a data safety monitoring board or an advisory board for AZD, Gilead, Infinity, MSD, Bristol Myers Squibb, Nanostring, Incyte, and Roche. YZ is an employee of Merck & Co., Inc. MF and PM are employees of Merck & Co., Inc., and stockholders of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ. BDS has received funding for the current manuscript from Merck & Co., Inc.; received research funding from Merck & Co., Inc.; has been a consultant for Jazz Pharmaceuticals, Novartis, and Pfizer; and has participated on a data safety monitoring board or an advisory board for Celgene, a subsidiary of Bristol Myers Squibb.
Publisher Copyright:
© The work of Yayan Zhang, Mohammed Farooqui and Patricia Marinello is © 2022 Merck & Co., Inc. Published by Informa UK Limited, trading as Taylor & Francis Group The work of Guillermo Garcia-Manero, Vincent Ribrag and B. Douglas Smith is © 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
PY - 2022
Y1 - 2022
N2 - The phase 1b multicohort KEYNOTE-013 study assessed the safety and antitumor activity of pembrolizumab given at 10 mg/kg/day every 2 weeks for up to 2 years in hematologic malignancies, including myelodysplastic syndromes (MDS) refractory to a hypomethylating agent (HMA). Primary outcomes were safety and objective response rate per International Working Group 2006 criteria. By June 26, 2020, 28 patients were enrolled; median duration of follow-up was 5.6 months (range, 1–78), and 25 patients (89%) had died. Treatment-related adverse events occurred in 10 patients (36%), including 2 (7%) treatment-related discontinuations. No patient achieved complete or partial response. Five patients (19%) had bone marrow complete response, 12 (44%) stable disease, 10 (37%) progressive disease, 6 (22%) cytogenetic response, and 5 (19%) hematologic improvement. Median overall survival (OS) was 6.0 months (95% CI, 4–12); the overall 2-year OS rate was 17%. Pembrolizumab had manageable safety and clinical activity in patients with HMA-refractory MDS. This trial was registered at www.clinicaltrials.gov as #NCT01953692.
AB - The phase 1b multicohort KEYNOTE-013 study assessed the safety and antitumor activity of pembrolizumab given at 10 mg/kg/day every 2 weeks for up to 2 years in hematologic malignancies, including myelodysplastic syndromes (MDS) refractory to a hypomethylating agent (HMA). Primary outcomes were safety and objective response rate per International Working Group 2006 criteria. By June 26, 2020, 28 patients were enrolled; median duration of follow-up was 5.6 months (range, 1–78), and 25 patients (89%) had died. Treatment-related adverse events occurred in 10 patients (36%), including 2 (7%) treatment-related discontinuations. No patient achieved complete or partial response. Five patients (19%) had bone marrow complete response, 12 (44%) stable disease, 10 (37%) progressive disease, 6 (22%) cytogenetic response, and 5 (19%) hematologic improvement. Median overall survival (OS) was 6.0 months (95% CI, 4–12); the overall 2-year OS rate was 17%. Pembrolizumab had manageable safety and clinical activity in patients with HMA-refractory MDS. This trial was registered at www.clinicaltrials.gov as #NCT01953692.
KW - Hypomethylating agents
KW - PD-1 inhibitor
KW - myelodysplastic syndromes
KW - pembrolizumab
UR - http://www.scopus.com/inward/record.url?scp=85126043499&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85126043499&partnerID=8YFLogxK
U2 - 10.1080/10428194.2022.2034155
DO - 10.1080/10428194.2022.2034155
M3 - Article
C2 - 35244520
AN - SCOPUS:85126043499
SN - 1042-8194
VL - 63
SP - 1660
EP - 1668
JO - Leukemia and Lymphoma
JF - Leukemia and Lymphoma
IS - 7
ER -