Dataset Information

Novel immune directed therapies in myelodysplastic syndromes and acute myeloid leukemia.

ABSTRACT:

Purpose of review

Therapies that target the immune system are increasingly used across oncology, including in hematologic malignancies such as myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). While allogeneic transplant has been a key therapy in these cancers, new approaches that target the immune system are being explored including immune checkpoint therapies, antibody-drug conjugates, and cellular therapies.

Recent findings

This review outlines updates in the preclinical rationale for immune directed therapies in MDS and AML, as well as recent clinical trials exploring these therapies. This manuscript summarizes the development of therapies targeting T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3) and CD47, which are being evaluated in late phase studies in MDS and AML. It also reviews the landscape of other immune based therapies including antibody-drug conjugates, chimeric antigen receptor-T cells, bispecific antibodies, and tumor vaccines.

Summary

The treatment landscape in MDS and AML is rapidly changing; with a goal of improving the quality and duration of responses, a number of immune based therapies are under investigation. This review outlines recent advances with these therapies as well as some of the challenges that remain to incorporate them into leukemia care.

SUBMITTER: Brunner AM

PROVIDER: S-EPMC10017015 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Novel immune directed therapies in myelodysplastic syndromes and acute myeloid leukemia.

Brunner Andrew M AM

Current opinion in hematology 20221223 2

<h4>Purpose of review</h4>Therapies that target the immune system are increasingly used across oncology, including in hematologic malignancies such as myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). While allogeneic transplant has been a key therapy in these cancers, new approaches that target the immune system are being explored including immune checkpoint therapies, antibody-drug conjugates, and cellular therapies.<h4>Recent findings</h4>This review outlines updates in the pr ...[more]

PMID: 36728945

Similar Datasets

Project description:BackgroundThe molecular determinants of clinical responses to decitabine therapy in patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) are unclear.MethodsWe enrolled 84 adult patients with AML or MDS in a single-institution trial of decitabine to identify somatic mutations and their relationships to clinical responses. Decitabine was administered at a dose of 20 mg per square meter of body-surface area per day for 10 consecutive days in monthly cycles. We performed enhanced exome or gene-panel sequencing in 67 of these patients and serial sequencing at multiple time points to evaluate patterns of mutation clearance in 54 patients. An extension cohort included 32 additional patients who received decitabine in different protocols.ResultsOf the 116 patients, 53 (46%) had bone marrow blast clearance (<5% blasts). Response rates were higher among patients with an unfavorable-risk cytogenetic profile than among patients with an intermediate-risk or favorable-risk cytogenetic profile (29 of 43 patients [67%] vs. 24 of 71 patients [34%], P<0.001) and among patients with TP53 mutations than among patients with wild-type TP53 (21 of 21 [100%] vs. 32 of 78 [41%], P<0.001). Previous studies have consistently shown that patients with an unfavorable-risk cytogenetic profile and TP53 mutations who receive conventional chemotherapy have poor outcomes. However, in this study of 10-day courses of decitabine, neither of these risk factors was associated with a lower rate of overall survival than the rate of survival among study patients with intermediate-risk cytogenetic profiles.ConclusionsPatients with AML and MDS who had cytogenetic abnormalities associated with unfavorable risk, TP53 mutations, or both had favorable clinical responses and robust (but incomplete) mutation clearance after receiving serial 10-day courses of decitabine. Although these responses were not durable, they resulted in rates of overall survival that were similar to those among patients with AML who had an intermediate-risk cytogenetic profile and who also received serial 10-day courses of decitabine. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT01687400 .).

Dataset Information

Novel immune directed therapies in myelodysplastic syndromes and acute myeloid leukemia.

Purpose of review

Recent findings

Summary

Publications

Novel immune directed therapies in myelodysplastic syndromes and acute myeloid leukemia.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets