Amer Zeidan, MBBS

A panelist discusses how ASCO 2025's most important breakthrough was the oral decitabine plus venetoclax combination, representing a potential paradigm shift if approved by the FDA, while highlighting that menin inhibitors (including the already-approved revumenib and pipeline agents like ziftomenib, bleximenib, and enzomenib) are the most exciting emerging therapies targeting 40% to 50% of patients with acute myeloid leukemia with NPM1 mutations or KMT2A rearrangements, though significant therapeutic gaps remain for challenging subgroups like TP53-mutated disease.

A panelist discusses how a large propensity score–matched analysis of 1300 patients aged 60-75 found similar all-cause mortality between intensive chemotherapy and azacitidine plus venetoclax, but with lower adverse events in the azacitidine-venetoclax group, suggesting that treatment selection should be individualized based on patient fitness, genetic mutations, transplant candidacy, and patient preferences for time-limited vs continuous therapy, while emphasizing the need for prospective randomized trials to definitively guide treatment decisions in this age group.

A panelist discusses how oral combination therapy with decitabine-cedazuridine plus venetoclax shows activity in the relapsed/refractory acute myeloid leukemia setting, achieving responses even in patients with TP53 mutations, prior venetoclax exposure, or prior transplant, though the presenter questions whether 10 days of decitabine offers advantages over the standard 5-day regimen and emphasizes that these oral therapies can effectively extend beyond frontline treatment into salvage settings.

A panelist discusses how the shift from intravenous to oral AML therapies addresses significant quality-of-life concerns by eliminating the burden of spending 7 days per month in clinics for infusions (which can consume nearly half of a patient's remaining 15-month median survival time), while also improving clinic efficiency, though implementation requires careful attention to patient adherence, insurance coverage disparities that may penalize oral medications with higher co-pays, and monitoring for drug interactions.

A panelist discusses how the ASCERTAIN-V study demonstrated that an all-oral combination of decitabine-cedazuridine plus venetoclax achieved a 47% complete response rate and 15.5-month median overall survival in older, unfit AML patients, representing a potential new standard of care that eliminates the need for intravenous infusions and significantly reduces clinic time burden while serving as a backbone for future oral combination therapies.

A panelist discusses how the highest unmet needs in acute myeloid leukemia include treatments for patients with refractory and relapsed disease, addressing poor outcomes in patients with TP53 mutations and MECOM rearrangements, while emerging trends focus on combination therapies (doublets, triplets, quadruplets), the shift toward more convenient oral therapies, increased emphasis on minimal residual disease negativity as an end point, and expanded transplant eligibility for older patients aged into their mid to late 70s.