Defining HMA Failure and Bridging to Transplant/Introduction of CML Case

This segment continues the discussion of high-risk MDS management, focusing on how clinicians define failure of HMAs and determine next steps in therapy, particularly in patients with TP53 mutations. Dr. Shastri emphasizes that for this 72-year-old patient with limited treatment options, oral HMAs are appropriate to improve quality of life by reducing clinic visits, especially given renal insufficiency that may limit clinical trial eligibility. In practice, she expects potential efficacy by the 3rd or 4th cycle but prefers to evaluate response over 6 to 8 cycles before considering therapy failure. This approach allows sufficient time to assess clinical benefit while preparing the patient for potential allogeneic stem cell transplant.

Dr. Boccia describes that transplant centers, such as that at Johns Hopkins, may use early cycles of HMA therapy to “soften the marrow” prior to transplant rather than requiring full remission, reinforcing the concept that stable disease can still justify proceeding to transplant. If the patient shows only stable disease after six cycles, alternative strategies, such as adding venetoclax to HMA therapy, may be considered, with clinical trials as a secondary option depending on renal function and eligibility. The panel also discusses data suggesting that patients with TP53 mutations may benefit from combination therapies, which can increase response rates and potentially improve bridging to transplant, though overall survival gains remain uncertain.