Phase II REFINE and phase III TRANSFORM-2 studies: Navitoclax ± ruxolitinib in MF

Results from an analysis of the open-label, phase II REFINE (NCT03222609) and the randomized, open-label, phase III TRANSFORM-2 (NCT04468984) studies, evaluating navitoclax ± ruxolitinib (REFINE) and navitoclax + ruxolitinib vs best available therapy (BAT; TRANSFORM-2) in patients with Janus kinase inhibitor (JAKi)-treated relapsed/refractory (R/R) myelofibrosis (MF), were published in Leukemia & Lymphoma by Rampal et al. In both studies, the primary endpoint was ≥35% spleen volume reduction (SVR35) at Week 24.

Key data: Patients who received navitoclax monotherapy from REFINE cohort 2 (n = 34) and who received navitoclax + ruxolitinib (n = 145) or BAT (n = 132) from TRANSFORM-2 were included. At Week 24, 12% (95% confidence interval [CI], 3.30–27.45) of patients receiving navitoclax monotherapy and 17% (95% CI, 10.92–24.49) of patients receiving navitoclax + ruxolitinib attained an SVR35 response vs 7% (95% CI, 3.21–12.74) of patients receiving BAT. A ≥50% reduction in total symptom score (TSS50) at Week 24 was achieved in 9%, 32%, and 12% of patients receiving navitoclax monotherapy, navitoclax + ruxolitinib, and BAT, respectively. The most common Grade ≥3 adverse events (AEs) with navitoclax monotherapy were thrombocytopenia / decreased platelet count (32%), neutropenia / decreased neutrophil count (32%), serious infections (15%), and drug-related hepatic disorders (24%). The most common Grade ≥3 AEs with navitoclax + ruxolitinib vs BAT were thrombocytopenia / decreased platelet count (45% vs 11%) and anemia (39% vs 27%).

Key learning: In this analysis, higher SVR35 rates with navitoclax + ruxolitinib vs BAT (and indirectly with navitoclax monotherapy) suggest a complementary effect of the combination in patients with R/R MF, supporting further investigation of combination therapies in this difficult-to-treat population.