The phase 3 TRANSFORM-1 trial (NCT04472598) randomised 252 participants with untreated intermediate- or high-risk MF and measurable splenomegaly to the Bcl-2 inhibitor navitoclax or a placebo. All participants received the JAK inhibitor ruxolitinib. The primary endpoint was SVR35 at week 24 and Prof. Naveen Pemmaraju (MD Anderson Cancer Center, TX, USA) presented the findings1.
The primary endpoint was met by 63 % of the participants in the navitoclax arm and by 32 % in the placebo arm, a significant difference (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 receivers and 42 % of the placebo receivers.
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 ruxolitinib plus placebo in this population with MF, without showing new safety signals.
Medical writing support was provided by Robert van den Heuvel.