Navitoclax plus ruxolitinib leads to spleen volume reductions in myelofibrosis

JAK inhibitor-naïve participants with myelofibrosis benefitted from a regimen of navitoclax plus ruxolitinib compared with ruxolitinib and a placebo in the phase 3 TRANSFORM-1 trial.

The phase 3 TRANSFORM-1 trial (NCT04472598) randomised 252 participants with untreated intermediate- or high-risk myelofibrosis and measurable splenomegaly to the Bcl-2 inhibitor navitoclax or placebo plus ruxolitinib. All participants received the JAK inhibitor ruxolitinib. The primary endpoint was a 35% spleen volume reduction (SVR35) at week 24 and Prof. Naveen Pemmaraju (MD Anderson Cancer Center, TX, USA) presented the findings [1].

The primary endpoint was met by 63% of the participants in the navitoclax arm and 32% in the placebo arm (P<0.0001). “This finding was consistent across subgroups,” highlighted Prof. Pemmaraju. Almost 50% of the included participants had high molecular risk profiles. In this subgroup of participants, the primary endpoint was met by 59% and 41%, favouring the navitoclax over the placebo arm. Also, variant allele frequency reductions of at least 20% at any time were seen in 57% of the navitoclax and 42% of the placebo receivers. Survival data was presented for the high molecular risk profile participants and the median progression-free survival was 25.2 months in the experimental arm versus 22.9 months in the placebo arm.

The most frequently occurring adverse events in the navitoclax arm were thrombocytopenia, anaemia, diarrhoea, and neutropenia, all observed in >30% of the participants. Finally, serious adverse events were seen in 28% of the participants on navitoclax and 38% on placebo.

Navitoclax plus ruxolitinib resulted in a 2-fold improvement of SVR35 at week 24 compared with placebo plus ruxolitinib in this population with myelofibrosis, without showing new safety signals.

1. Pemmaraju N, et al. Efficacy and safety of navitoclax in combination with ruxolitinib versus ruxolitinib plus placebo in patients with untreated myelofibrosis in the phase 3 randomized, double-blind TRANSFORM-1 study. S222, EHA congress 2024, 13–16 June, Madrid, Spain.

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Posted on 12 August 2024