Leukemia Relapse: PD-1 Inhibition Shows Mixed Results
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.
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We remain steadfast in our conviction that the formula for lasting success is to stay focused, think long-term, and do business in a financially, socially, and environmentally responsible way. With a US presence spanning 40 years, Novo Nordisk US is headquartered in New Jersey and employs over 10,000 people throughout the country across 12 manufacturing, R&D and corporate locations in eight states plus Washington DC. For more information, visit Facebook, Instagram, and X. Novo Nordisk is committed to the responsible use of our semaglutide-containing medicines which represent distinct products with different indications, dosages, prescribing information, titration schedules, and delivery forms. These products are not interchangeable and should not be used outside of their approved indications. Learn more at References Wegovy® (semaglutide) injection [package insert]. Plainsboro, NJ: Novo Nordisk Inc. Sanyal AJ, Newsome PN, Kliers I, et al. Phase 3 Trial of Semaglutide in Metabolic Dysfunction-Associated Steatohepatitis. N Engl J Med. 2025;392(21):2089-2099. doi:10.1056/NEJMoa2 413258 Younossi ZM, Mangla KK, Chandramouli AS, et al. Estimating the economic impact of comorbidities in patients with MASH and defining high-cost burden in patients with noncirrhotic MASH. Hepatol Commun. 2024;8(8):e0488. doi:10.1097/HC9.00000 00000000488 Allen AM, Charlton M, Cusi K, et al. Guideline-based management of metabolic dysfunction-associated steatotic liver disease in the primary care setting. Postgrad Med. 2024;136(3):229-245. doi:10.1080/00325481.2024.2325332 Kugelmas M, Noureddin M, Gunn N, et al. The use of current knowledge and non-invasive testing modalities for predicting at-risk non-alcoholic steatohepatitis and assessing fibrosis. Liver Int. 2023;43(5):964-974. doi:10.1111/liv.15555 Quek J, Chan KE, Wong ZY, et al. Global prevalence of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in the overweight and obese population: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 2023;8(1):20-30. doi:10.1016/S2468-1253(22)00317-X Newsome PN, Sanyal AJ, Engebretsen KA, et al. Semaglutide 2.4 mg in participants with metabolic dysfunction-associated steatohepatitis: baseline characteristics and design of the phase 3 ESSENCE trial. Aliment Pharmacol Ther. 2024;60(11-12):1525-1533. doi:10.1111/apt.18331 National Institute of Diabetes and Digestive and Kidney Diseases. Definition & facts of NAFLD & NASH. Accessed June 13, 2025. Sheka AC, Adeyi O, Thompson J, et al. Nonalcoholic steatohepatitis: a review. JAMA. 2020;323(16):1619. doi:10.1001/jama.2020.5249 Younossi ZM, Koenig AB, Abdelatif D, et al. Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016;64(1):73-84. doi:10.1002/hep.28431 Wegovy® is a registered trademark of Novo Nordisk A/S. Novo Nordisk is a registered trademark of Novo Nordisk A/S. All other trademarks, registered or unregistered, are the property of their respective owners. © 2025 Novo Nordisk All rights reserved. US25SN00042 August 2025 View original content to download multimedia: SOURCE NOVO NORDISK INC. Error in retrieving data Sign in to access your portfolio Error in retrieving data Error in retrieving data Error in retrieving data Error in retrieving data
