Interpreting CP Data, Secondary Mutations, and Bridging Strategies to Transplant

Segment 5 explores more deeply the clinical implications of CP-based regimens and how they compare with venetoclax-based therapy when preparing patients with AML for allogeneic transplant. The panelists reflect on data showing unexpectedly strong post-transplant survival among patients treated on phase III CP-351 trials, particularly in AML with MDS-related changes. Some studies report 40% survival at 10 years in certain subgroups, results rarely observed historically in MDS-related AML. Although these findings raise the question of whether CP regimens provide uniquely beneficial disease control before transplant, the panel notes that patient numbers are small, limiting definitive conclusions.

The experts revisit the retrospective Hopkins comparison of venetoclax-based therapy versus intensive chemotherapy before transplant. Although encouraging, they caution that the data remain non-randomized and susceptible to bias. Still, for many clinicians this retrospective evidence provides enough reassurance that venetoclax can serve as a suitable bridge to transplant in selected patients, particularly those with secondary-type mutations, who appear to derive meaningful benefit from venetoclax-based regimens.

The speakers also discuss puzzling aspects of older CTC (or CP-like) transplant data, including how post-transplant survival advantages were achieved. They question whether improved non-relapse mortality, from fewer infections or reduced pre-transplant toxicity, fully explains the outcomes, or whether deeper remissions might also play a role. Because earlier trials lacked sophisticated MRD assessments, it remains unclear whether CP regimens produce molecularly superior remissions.

The segment then shifts to the broader question of designing optimal induction approaches for younger or fit patients. Although paradigm-shifting trials may expand the role of lower-intensity induction, intensive chemotherapy still offers strong remission depth and is likely to remain important for many transplant candidates. Ultimately, the group underscores that treatment selection must integrate disease biology, mutation profile, fitness, and transplant goals rather than relying on a one-size-fits-all approach.