TRANSFORM-1 phase 3 study: efficacy and safety of navitoclax plus ruxolitinib in patients with untreated myelofibrosis.

Navitoclax plus ruxolitinib significantly increases the proportion of patients with ≥35% spleen volume reduction at week 24 in untreated myelofibrosis, reaching 63.2% versus 31.5%.

• Why it matters: Effective treatment options for untreated myelofibrosis are limited, and improving spleen reduction is crucial for patient outcomes. Understanding the efficacy of combination therapies can guide clinical decisions and improve patient management.
• What they did: The phase 3 TRANSFORM-1 trial randomized 252 JAK inhibitor-naïve adults with intermediate-2 or high-risk myelofibrosis to receive navitoclax plus ruxolitinib or placebo plus ruxolitinib, assessing spleen volume reduction and symptom scores over a median follow-up of 20.3 months.
• The result: Navitoclax plus ruxolitinib doubled the rate of spleen volume reduction at week 24 and at any time point, though it was associated with higher hematologic toxicity; cytopenias were manageable and reversible.