Ruxolitinib and Erythropoiesis-Stimulating Agents for Myelofibrosis

Atlanta—A posthoc analysis of a phase 3 study found that patients with myelofibrosis who were receiving erythropoiesis-stimulating agents (ESAs) tolerated the concomitant use of ruxolitinib, a potent janus kinase 1 and 2 inhibitor. The authors indicated there were no safety concerns associated with the combination therapy, although they suggested further analyses may be necessary because using ESAs to treat anemia is common.

Results were presented during a poster session at the ASH meeting. The poster was titled The Use of Erythropoiesis-Stimulating Agents with Ruxolitinib in Patients with Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, and Post-Essential Thrombocythemia Myelofibrosis.

The authors noted that in the COMFORT (Controlled Myelofibrosis Study with Oral JAK Inhibitor Treatment) I and II trials, ruxolitinib reduced splenomegaly and improved myelofibrosis-related symptoms and quality of life. In November 2011, the FDA approved the drug to treat patients with intermediate- or high-risk myelofibrosis.

In the COMFORT studies, anemia was among the most common adverse events; 1 patient discontinued taking ruxolitinib due to anemia. In this analysis, the authors were interested in the safety and efficacy of ruxolitinib in patients from COMFORT-II who received concomitant ESAs. They said some patients take ESAs to manage anemia, although the researchers in COMFORT-II discouraged using ESAs due to a possible increase in spleen size.

COMFORT-II included 219 patients who were randomized in a 2:1 ratio to receive 15 or 20 mg of ruxolitinib twice daily (n=146 patients) or best available therapy (n=73 patients). Patients had primary myelofibrosis, post-polycythemia vera myelofibrosis, or post-essential thrombocythemia myelofibrosis and ≥2 International Prognostic Scoring System risk factors.

Of the patients in the ruxolitinib group, 13 also took ESAs: 9 took epoetin alfa, 3 took darbepoetin alfa, and 1 took epoetin NOS. Patients received a median of 33 mg of ruxolitinib per day, and the mean exposure to the drug was similar in patients who took ESAs (114 weeks) and those who did not take ESAs (111 weeks).

Twelve of the 13 patients in the ESA group had sustained reductions in spleen volume from baseline when taking ruxolitinib before using ESAs. Of the 8 patients assessed 12 weeks after initiation of ESAs, 6 had increases in hemoglobin levels and 2 had decreases.

The rate of packed red blood cell transfusions per month 12 weeks before and after ESA use did not change for 8 patients, decreased for 2 patients, and increased for 3 patients. In addition, 11 patients had no substantial change in reticulocyte counts within 12 weeks before and after taking ESAs. Data were unavailable for the other 2 patients.

Adverse events were similar for patients taking ESAs and those not taking ESAs. Of the 13 patients, 8 had serious adverse events; 3 events in 2 patients were possibly related to ruxolitinib, according to the authors. One patient had general health deterioration and respiratory tract infection, while another had anemia. The authors did not attribute the concomitant use of ESAs to serious adverse events such as thrombosis, hypertension, and spleen rupture.

This study was funded by Novartis.