Dr Gerds on Updated Data for Pelabresib Plus Ruxolitinib in JAK Inhibitior–Naive Myelofibrosis

Aaron Gerds, MD, assistant professor in medicine, Hematology and Medical Oncology, Cleveland Clinic Taussig Cancer Institute, discusses updated efficacy and safety results from the phase 3 MANIFEST-2 trial (NCT04603495) of pelabresib (CPI-0610) plusruxolitinib (Jakafi) in patients with JAK inhibitor–naive myelofibrosis.

Previously reported data from the randomized, double-blind, placebo-controlled trial, showed that the combination of pelabresib and ruxolitinib produced a statistically significant and clinically meaningful improvement in spleen volume reduction of at least 35% (SVR35) from baseline vs placebo plus ruxolitinib in patients with treatment-naive disease.

At the 2024 ASCO Annual Meeting, Gerds and colleagues reported data reaffirming these initial topline results, emphasizing their consistency over time. Among patients who achieved SVR35, 13.4% in the combination arm lost their splenic response compared with 27.8% of patients treated in the placebo arm.

Notably, the proportion of patients achieving both SVR35 and a reduction in tumor symptom score of at least 50% (TSS50) was also evaluated, Gerds states. In the combination therapy group, 40.2% of patients achieved both end points vs 18.5% with ruxolitinib alone, he reports. Gerds posits that the difference in rates of TSS50 may not be as pronounced between the combination therapy and ruxolitinib alone because single-agent ruxolitinib is highly effective in reducing symptoms; however, the higher proportion of patients achieving both end points with the combination therapy is noteworthy, he explains.

Furthermore, data beyond the 24-week mark indicate that the responses remain durable, with no new adverse effects (AEs) emerging, Gerds details. This indicates that the combination therapy remains safe and effective, although longer follow-up is necessary to fully confirm the durability of these responses, he adds.

Overall, the combination therapy shows promise in achieving significant and durable responses in a higher proportion of patients compared with ruxolitinib alone. Continuous follow-up and monitoring of AEs will be key in confirming the long-term safety and efficacy of this treatment approach.