5 days ago
Leukemia Relapse: PD-1 Inhibition Shows Mixed Results
TOPLINE:
Programmed death-1 (PD-1) inhibition with pembrolizumab led to durable remission in 31.3% of patients with early acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) relapse after hematopoietic cell transplantation (HCT). Mixed CD3 chimerism predicted response, but 37.5% developed severe graft-vs-host disease (GVHD).
METHODOLOGY:
A prospective phase 1B clinical trial enrolled 16 patients with AML (n = 12) and MDS (n = 4) who experienced relapse after HCT, with a median time to relapse of 5.5 months and median pretreatment bone marrow blast percentage of 21.5%.
Participants received 200 mg pembrolizumab intravenously every 21 days for up to four cycles (induction), with responding patients eligible for maintenance therapy up to 1 year.
Primary objectives included assessment of safety, overall response rate to pembrolizumab with or without subsequent chemotherapy, and rates of GVHD or clinically significant immune-mediated toxicity.
Response evaluation occurred through bone marrow examination on day 35 (after cycle 2) and day 77 (after cycle 4), with complete remission defined as bone marrow blasts less than 5% and absence of circulating blasts.
TAKEAWAY:
The overall response rate was 31.3%, consisting of three complete remissions (18.8%) and two partial remissions (13.5%), with a median response duration of 610 days.
Patients with mixed CD3 chimerism showed significantly higher response rates compared to those with full donor chimerism (50% vs 0%; P = .03).
Severe (grades 3-4) GVHD developed in 37.5% of patients, with most cases resistant to corticosteroids and contributing to death in 25% of participants.
The 1-year overall survival was 37.5% and event-free survival was 31.3%, with AML patients showing 1-year overall survival of 50.0%.
IN PRACTICE:
'PD-1 inhibition led to durable remission in on -third of the patients experiencing early relapse after HCT, suggesting that this approach may augment the GVL [graft-vs-leukemia] response. Responses were exclusively observed in the setting of mixed CD3 donor chimerism. Immune toxicities (GVHD) were a barrier to successful treatment outcome,' the authors of the study wrote.
'The results of the study highlight the challenge of attempting to dissect the graft-vs-leukemia effect from immunologic toxicity in patients with HCT,' Roman M. Shapiro and Robert J. Soiffer, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, said in a press release.
SOURCE:
The study was led by John M. Magenau, Transplantation and Cell Therapy Program, University of Michigan Rogel Cancer Center in Ann Arbor, Michigan. It was published online on August 12 in Blood Advances.
LIMITATIONS:
According to the authors, the small sample size limited their ability to determine the extent to which pembrolizumab could separate graft-vs-leukemia effects from GVHD. The researchers note that, while some patients achieved response without GVHD, the limited cohort size may have confounded interpretation of significant variables, including response patterns in patients with high blast percentage, very early relapse, monosomal karyotype, or TP53 mutations.
DISCLOSURES:
Magenau declared receiving support through a National Institutes of Health career development award (K23AI123595) and a Rogel Cancer Center Scholarship. The study was supported by a research grant (54053) from the Investigator-Initiated Studies Program of Merck Sharp & Dohme LLC.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
