Pelabresib Combined With Ruxolitinib in MF

In the phase 2 MANIFEST trial, John Mascarenhas, MD, and colleagues evaluated pelabresib, an oral bromodomain and extraterminal domain inhibitor, combined with ruxolitinib for the treatment of myelofibrosis (MF) in Janus kinase inhibitor-naïve patients.

According to Dr. Mascarenhas, the combination was generally well-tolerated and yielded durable improvements in myelofibrosis characteristics. The results were presented at the 64th ASH Annual Meeting and Exposition.

A total of 84 patients (median years of age, 68 [range, 37-85 years]) received at least 1 dose of pelabresib and ruxolitinib. Baseline Dynamic International Prognostic Scoring System scores were intermediate-1 (24%), intermediate-2 (61%), and high risk (16%). Participants’ spleen volume was evaluated by computed tomography or magnetic resonance imaging every 12 weeks.

Pelabresib Plus Ruxolitinib Effective in Phase 2 MF Trial

The primary end point was ≥35% spleen volume reduction (SVR35) from baseline after 24 weeks, while other end points included ≥50% total symptom score reduction (TSS50), duration of spleen response, pharmacokinetics, safety, transfusion independence, and changes from baseline in bone marrow fibrosis.

A total of 57 of 94 (68%) and 47 of 79 (60%) patients achieved SVR35 at week 24 and week 48, respectively. SVR35 at any time was reported in 67 of 84 (80%) patients, and 87% of patients with SVR35 sustained a response until data cutoff. The median time to SVR35 response was 12 weeks, and the median spleen volume change was -50% (range, –84.4 to 27.9) at week 24.

In addition, 46 of 82 (56%) patients achieved TSS50 at week 24 and 34 of 79 (43%) at week 48, with 81% of patients achieving TSS50 at any time. The median change in TSS at week 24 was -59% (range, –100 to 225). Finally, the most common hematologic treatment-emergent adverse event of any grade was thrombocytopenia in 52% of patients, of which 12% were grade 3 or higher.

Dr. Mascarenhas and colleagues suggested the combined regimen in this treatment arm of the MANIFEST trial “showed durable improvements in spleen volume, total symptom score and [bone marrow] fibrosis, and was generally well-tolerated.” They noted that the phase 3 MANIFEST-2 study was currently enrolling.

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