Navitoclax monotherapy or in combination with ruxolitinib in patients with JAK2 inhibitor-treated myelofibrosis: results from the phase 2 REFINE and phase 3 TRANSFORM-2 studies

The Phase 2 REFINE and Phase 3 TRANSFORM-2 trials evaluated the efficacy and safety of navitoclax—a BCL-2 family inhibitor—as monotherapy (NAV; N = 34) and in combination with ruxolitinib (NAV + RUX; n = 146) versus best available therapy (BAT; n = 149), respectively, in patients with myelofibrosis with prior JAKi treatment. The primary endpoint in both studies, ≥35% spleen volume reduction (SVR35) at Week 24, was achieved by 12% of patients treated with NAV monotherapy (REFINE) and 17%, and 7% of patients treated with NAV + RUX, and BAT, respectively (TRANSFORM-2). The most common adverse event in both studies leading to NAV dose reduction or interruption was thrombocytopenia. Higher SVR35 rates for NAV + RUX compared with BAT (and indirectly with NAV monotherapy) suggest a complementary effect of NAV + RUX. These preliminary findings highlight the potential for novel combination treatments to improve outcomes for relapsed or refractory patients with myelofibrosis. (ClinicalTrials.gov identifier: NCT03222609 [REFINE]; NCT04468984 [TRANSFORM-2]).