In the Phase III TRANSFORM-1 trial of navitoclax plus ruxolitinib versus placebo plus ruxolitinib in JAK inhibitor-naïve myelofibrosis, what were the key results, and why does the speaker suggest reconsidering trial endpoints?
Both SVR35 and symptom burden improved significantly, so the speaker argues spleen and symptoms remain sufficient endpoints for combination therapies.
The SVR35 primary endpoint was met (roughly 60% or more versus about 30%), but the symptom benefit was not statistically significant, a pattern seen with other combinations; the speaker suggests the field consider endpoints such as PFS, EFS, OS, MRD or biochemical markers of disease modification.
Neither SVR35 nor symptom burden improved, so the speaker argues BCL-XL inhibition should be abandoned in myelofibrosis.