Ongoing Research and Future Perspectives in Relapsed/Refractory AML

Opinion
Video

Clinical insights on the evolving treatment landscape for patients with relapsed/refractory acute myeloid leukemia, with a focus on ongoing research and unmet needs.

This is a video synopsis/summary of an OncView® featuring Ghayas C. Issa, MD.

Issa states menin inhibitors are the most exciting advance in treating KMT2A-rearranged and NPM1-mutant acute myeloid leukemia (AML), with combination strategies offering the greatest potential to improve outcomes. Combining menin inhibitors with standard of care like venetoclax or other targeted therapies such as FLT3 or IDH inhibitors could be impactful, as could combinations with investigational epigenetic regulators. Immunotherapies like antibody-chemotherapy conjugates, NK cells, or bispecific T-cell engagers may also prove promising in AML.

Issa stresses the need for accurate molecular profiling at AML relapse to guide therapy selection. Targeted sequencing is important to check for mutations acquired at relapse, like FLT3, that affect prognosis and treatment options. Fluorescent in situ hybridization testing can detect KMT2A rearrangements potentially missed by standard karyotyping. Other newer biomarkers that may predict menin inhibitor response deserve routine testing moving forward as well.

Menin inhibitors represent the biggest AML advance since venetoclax approval. Single-agent studies for regulatory approval in relapsed/refractory NPM1-mutant and KMT2A-rearranged leukemias are underway. The next step is expanding their reach to other AML subtypes with similar targetable gene expression. Further combining menin inhibitors with venetoclax or hypomethylating agents plus venetoclax shows early promise even in the relapse/refractory setting. Soon this can be taken to frontline treatment, possibly combined with FLT3 inhibitors. Over the next decades, menin inhibitors could transform the treatment landscape for a majority of AML cases.

Video synopsis is AI-generated and reviewed by Cancer Network® editorial staff.

Recent Videos
Yale’s COPPER Center aims to address disparities and out-of-pocket costs for patients, thereby improving the delivery of complex cancer treatment.
Non-Hodgkin lymphoma and other indolent forms of disease may require sequencing new treatments for years or decades, said Scott Huntington, MD, MPH, MSc.
Fixed-duration therapy may be more suitable for younger patients, while continuous therapy may benefit those who are older with more comorbidities.
Determining the molecular characteristics of one’s disease may influence the therapy employed in the first line as well as subsequent settings.
A 2-way communication between providers and patients may help facilitate dose modifications to help better manage adverse effects.
Treatment with AML depends on a variety of factors, including stage of treatment, transplant eligibility, and mutational status.
The medical characteristics of a patient may heavily factor into the selection of tyrosine kinase inhibition for the treatment of chronic myeloid leukemia.
Related Content
Among all patients with AML enrolled in the trial who received olutasidenib, the CR or CRh rate was 35%, with 55% of responders responding within 2 months.

Olutasidenib Maintains Durable Responses in IDH1+ AML for 5 Years

Tim Cortese
November 19th 2025
Article

Among all patients with AML enrolled in the trial who received olutasidenib, the CR or CRh rate was 35%, with 55% of responders responding within 2 months.

Jorge Cortes, MD, outlines the impact of imatinib in chronic myeloid leukemia and highlights future initiatives in the field.

Charting the Evolution of TKIs and Finding the Next Breakthrough in CML

Jorge E. Cortes, MD
October 13th 2025
Podcast

Jorge Cortes, MD, outlines the impact of imatinib in chronic myeloid leukemia and highlights future initiatives in the field.

Clinical data from the phase 1b/2 KOMET-001 trial support the agency’s approval of ziftomenib in this patient population.

FDA Approves Ziftomenib in R/R NPM1-Mutated Acute Myeloid Leukemia

Roman Fabbricatore
November 13th 2025
Article

Clinical data from the phase 1b/2 KOMET-001 trial support the agency’s approval of ziftomenib in this patient population.

Managing Cytokine Release Syndrome in Patients on CAR T-Cell Therapy

Managing Cytokine Release Syndrome in Patients on CAR T-Cell Therapy

Elizabeth Shpall, MD
May 29th 2019
Podcast

Ahead of the ASCO Annual Meeting, we discuss the assessment and management of cytokine release syndrome in patients with cancer with Elizabeth Shpall, MD.

Matched donor allogeneic CAR T for adult B-ALL: toxicity, efficacy, repeat dosing, and the importance of lymphodepletion

Matched donor allogeneic CAR T for adult B-ALL: toxicity, efficacy, repeat dosing, and the importance of lymphodepletion

American Society for Transplantation and Cellular Therapy
October 31st 2025
Article

Researchers have determined that matched allogeneic donor CD19 CAR T-cell therapy, delivered as a CAR-modified donor lymphocyte infusion, is safe and clinically active for adults with relapsed B-ALL following allogeneic transplant.

Clinical Implications Remain After Dasatinib CRL in CML/ALL

Clinical Implications Remain After Dasatinib CRL in CML/ALL

Ariana Pelosci
October 28th 2025
Article

The FDA's CRL for the HyNap formulation of dasatinib due to manufacturing issues does not affect the efficacy or availability of standard dasatinib.