Alternating Venetoclax Triplets Extend Survival in Older AML Patients

The management of acute myeloid leukemia in older adults remains a significant clinical challenge, as the median age at diagnosis is approximately 68 to 70 years [1]. While the combination of venetoclax and hypomethylating agents has become a standard for patients ineligible for intensive chemotherapy, real-world median overall survival often falls short of the benchmarks set in pivotal clinical trials [2]. A critical barrier to long-term survival in this population is the persistence of measurable residual disease (MRD), a threshold of less than one leukemic cell per 1,000 leukocytes that serves as a potent predictor of hematologic relapse [3, 4]. Current low-intensity regimens often fail to achieve MRD negativity in more than 30% to 40% of patients, particularly in molecular subtypes with inherent resistance to BCL-2 inhibition [4, 5]. Consequently, clinicians are increasingly investigating intensified combinations and alternating schedules to deepen responses and improve the feasibility of consolidative hematopoietic stem cell transplantation [6, 7]. A recent phase II study evaluates an alternating regimen designed to maximize cytoreduction while maintaining a manageable safety profile in this vulnerable cohort.