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Phase II Trial of Pembrolizumab after High-Dose Cytarabine in Relapsed/Refractory Acute Myeloid Leukemia.

Authors :
Zeidner JF
Vincent BG
Ivanova A
Moore D
McKinnon KP
Wilkinson AD
Mukhopadhyay R
Mazziotta F
Knaus HA
Foster MC
Coombs CC
Jamieson K
Van Deventer H
Webster JA
Prince GT
DeZern AE
Smith BD
Levis MJ
Montgomery ND
Luznik L
Serody JS
Gojo I
Source :
Blood cancer discovery [Blood Cancer Discov] 2021 Sep 10; Vol. 2 (6), pp. 616-629. Date of Electronic Publication: 2021 Sep 10 (Print Publication: 2021).
Publication Year :
2021

Abstract

Immune suppression, exhaustion, and senescence are frequently seen throughout disease progression in acute myeloid leukemia (AML). We conducted a phase II study of high-dose cytarabine followed by pembrolizumab 200 mg i.v. on day 14 to examine whether PD-1 inhibition improves clinical responses in relapsed/refractory (R/R) AML. Overall responders could receive pembrolizumab maintenance up to 2 years. Among 37 patients enrolled, the overall response rate, composite complete remission (CRc) rate (primary endpoint), and median overall survival (OS) were 46%, 38%, and 11.1 months, respectively. Patients with refractory/early relapse and those receiving treatment as first salvage had encouraging outcomes (median OS, 13.2 and 11.3 months, respectively). Grade ≥3 immune-related adverse events were rare (14%) and self-limiting. Patients who achieved CRc had a higher frequency of progenitor exhausted CD8 <superscript>+</superscript> T cells expressing TCF-1 in the bone marrow prior to treatment. A multifaceted correlative approach of genomic, transcriptomic, and immunophenotypic profiling offers insights on molecular correlates of response and resistance to pembrolizumab.<br />Significance: Immune-checkpoint blockade with pembrolizumab was tolerable and feasible after high-dose cytarabine in R/R AML, with encouraging clinical activity, particularly in refractory AML and those receiving treatment as first salvage regimen. Further study of pembrolizumab and other immune-checkpoint blockade strategies after cytotoxic chemotherapy is warranted in AML. See related commentary by Wei et al., p. 551 . This article is highlighted in the In This Issue feature, p. 549 .<br /> (©2021 American Association for Cancer Research.)

Details

Language :
English
ISSN :
2643-3249
Volume :
2
Issue :
6
Database :
MEDLINE
Journal :
Blood cancer discovery
Publication Type :
Academic Journal
Accession number :
34778801
Full Text :
https://doi.org/10.1158/2643-3230.BCD-21-0070