Mrinal S. Patnaik, MBBS

Mrinal S. Patnaik, MBBS, Chair of the Acute Leukemia and Myeloid Neoplasms Group and Scientific Director of the Epigenetics Developmental Laboratory and the Epigenomics Program at the Mayo Clinic, Rochester, Minnesota, offered his thoughts on the phase II study findings of ruxolitinib’s efficacy in chronic monomyelocytic leukemia (CMML).

He explained that CMML is a neoplasm that overlaps myelodysplastic syndrome and myeoloproliferative neoplasms, with proliferative and dysplastic subtypes. Although treatment with hypomethylating agents is the approach approved by the U.S. Food and Drug Administration, these drugs do not alter mutational allele burdens and have not clearly been shown to be effective in prospective clinical trials for proliferative subtypes. Patients with proliferative disease often develop splenomegaly and constitutional symptoms related to the same. Apart from hydroxyurea, there are limited management options for these symptoms, Dr. Patnaik noted.

“Biologically, given that CMML (especially RAS-mutant proliferative subtypes) has an inherent hypersensitivity to GM-CSF [granulocyte-macrophage colony-stimulating factor] and the fact that the JAK/STAT pathway is a major constituent of GM-CSF signaling, there is a clear rationale to test the safety and efficacy of JAK inhibitors for CMML,” he said.

“In this phase II study, Padron et al demonstrate a potential role, including safety data, for the JAK2 inhibitor ruxolitinib in managing splenomegaly and constitutional features in patients with CMML. This is an important and unmet area for these patients, and further randomized trials looking at spleen volume response and improvement in symptoms scores as primary endpoints are greatly encouraged,” he commented. 

DISCLOSURE: Dr. Patnaik has received research funding from Stemline Therapeutics and Kura Oncology and has served on the advisory board for CTI Pharmaceuticals.