Sonidegib–Ruxolitinib Combo Yields Modest Benefit Over Ruxolitinib Monotherapy for MF
Researchers have found that combining sonidegib with ruxolitinib for the treatment of JAK inhibitor-naive patients with myelofibrosis (MF) yields a relatively modest overall benefit compared with ruxolitinib alone (Blood Adv. 2020;4[13]:3063-3071).
Vikas Gupta, MD, Princess Margaret Cancer Centre, University of Toronto, Ontario, Canada, and colleagues conducted the open-label, phase 1b/2 study to establish the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of sonidegib plus ruxolitinib and evaluate spleen volume reduction at weeks 24 and 48 in 50 JAK inhibitor-naïve patients with MF.
Among the 23 patients in the dose-escalation phase of the trial, doses for sonidegib once daily and for ruxolitinib twice daily were 400 mg and 10 mg, respectively (level 1, n = 8); 400mg and 15 mg, respectively (level 2, n = 10); and 400 mg and 20 mg, respectively (level 3, n = 5).
The dose-limiting toxicity of increased blood creatine phosphokinase (grades 3 and 4) was observed in 2 patients at level 2.
Ultimately, the MTD/RP2D was determined to be sonidegib 400 mg daily plus ruxolitinib 20 mg twice daily.
Among the 27 patients in phase 1b expansion and phase 2 stage 1 of the trial, ≥35% reduction in spleen volume was observed in 44.4% and 29.6% patients by weeks 24 and 48, respectively. As of weeks 24 and 48, a ≥50% reduction in MF Symptom Assessment Form total symptom score was reported in 42.0% and 26.0% patients, respectively.
The most frequently reported treatment-related adverse events grade 3/4 were increased blood creatine phosphokinase (18%), anemia (14%), and thrombocytopenia (12%). A total of 4 deaths occurred due to multiple organ dysfunction syndrome, acute myeloid leukemia, MF progression, and aspiration pneumonia.
“Although well tolerated, this combination will not be further developed in MF patients due to modest overall benefit compared with historical ruxolitinib monotherapy,” concluded Dr Gupta and colleagues.—Hina M. Porcelli
