期刊
BLOOD CANCER DISCOVERY
卷 2, 期 6, 页码 616-629出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/2643-3230.BCD-21-0070
关键词
-
资金
- Investigator-Initiated Studies Program of Merck Sharp Dohme Corp.
The study demonstrated that pembrolizumab following high-dose cytarabine in relapsed/refractory AML patients was well-tolerated and feasible, showing promising clinical activity, especially in refractory AML and those receiving treatment as first salvage regimen. Further exploration of pembrolizumab and other immune-checkpoint blockade strategies post cytotoxic chemotherapy is recommended in AML.
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(+) 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. 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.
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