Intravenous infusion

Pelabresib plus ruxolitinib may be more efficient than monotherapy with janus kinase (JAK) inhibitors (JAKi) in JAKi treatment-naïve patients with myelofibrosis (MF), according to a new study published in the journal Blood Advances.

This finding was based on a matching-adjusted indirect comparison, which has been proposed as a validated method for indirect treatment comparison. The safety and efficacy of the combination therapy are also being tested in a placebo-controlled, randomized, double-blind, phase 3 clinical trial.

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A previous phase 2 clinical trial had shown that pelabresib plus ruxolitinib led to reductions in spleen volume and total symptom score from baseline in patients with MF. However, there have been no head-to-head clinical comparison between JAKi monotherapy and combination therapy with JAKi plus a bromodomain and extra terminal domain inhibitor (BETi) such as pelabresib. 

The present study, therefore, used an unanchored matching-adjusted indirect comparison analysis to compare reductions in spleen volume and total symptom score in the phase 2 study testing pelabresib plus ruxolitinib and in 3 clinical trials testing monotherapy with JAKi inhibitors in JAKi treatment-naïve patients with MF.

The results showed that response rate ratios above 1 were seen with the combination therapy compared to all JAKi monotherapies for spleen volume and total symptom score reductions. Moreover, improvements in total symptom score were apparent as early as week 12 from the start of treatment and were durable.

MF is a rare disease characterized by bone marrow scarring due to the production of excess fibrous tissue that interferes with the normal production of blood cells. 

The current standard of care for MF includes JAKi, including ruxolitinib, fedratinib, and pacritinib. However, these are often discontinued due to progressive disease and toxicities. 

Pelabresib is an experimental oral, small-molecule BETi. BETs regulate the transcription of genes integrating oncogenic signals. Therefore, their inhibition may modify biological pathways that may be critical in MF, such as megakaryocyte proliferation and differentiation.


Gupta V, Mascarenhas JO, Kremyanskaya M, et al. Matching-adjusted indirect comparison of pelabresib/ruxolitinib combination vs JAKi monotherapy in myelofibrosis. Blood Adv. Published online August 2, 2023. doi:10.1182/bloodadvances.2023010628