Targeted Combinations Transform AML Care

Abhishek Maiti, MD MD Anderson Cancer Center | Jorge Cortes, MD Georgia Cancer Center

January 1, 2026

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Key Points

  • FLT3 inhibitor–based combinations remain the most advanced and transformative targeted strategy in acute myeloid leukemia (AML).

  • Enthusiasm is growing for venetoclax-based regimens across both fit and unfit populations.

  • Early data showed encouraging results with menin inhibitors combined with azacitidine, venetoclax, and intensive chemotherapy in both frontline and relapsed settings.

Targeted therapy combinations, such as FLT3-, isocitrate dehydrogenase–, and menin-based regimens, have created excitement in the treatment of AML, where molecularly defined subsets have historically had poor outcomes.

Jorge Cortes, MD, of Georgia Cancer Center, joined Abhishek Maiti, MD, of The University of Texas MD Anderson Cancer Center, for a discussion during the 2025 ASH Annual Meeting, sharing insights on the shift toward combination strategies in the frontline setting alongside chemotherapy (7 + 3).

Although an early study of gilteritinib plus azacitidine was negative, combining FLT3 inhibitors with venetoclax is showing promise not only for FLT3-mutated and unfit patients but also potentially for younger patients, based on data from the meeting. However, Dr. Cortes noted that randomized studies are critical.

Another evolving area in AML involves menin inhibitor combinations. Although single-agent activity is strong, these therapies are unlikely to be used alone long term, according to Dr. Cortes. Early data combining menin inhibitors with azacitidine, venetoclax, and intensive chemotherapy in both frontline and relapsed settings have been encouraging, but additional studies are needed to define optimal sequencing and clinical positioning.

The experts went on to discuss safety concerns, including differentiation syndrome and tolerability with triplet regimens. In combination trials, differentiation syndrome appears less frequent, and inpatient induction allows for close monitoring, Dr. Cortes said. He and Dr. Maiti believe that, although benefit–risk considerations remain critical in favorable-risk disease, early data suggest these regimens are manageable and may become standard of care.