Ruxolitinib in Myelofibrosis Treatment and the COMFORT Trials


A review of data on the use of the JAK inhibitor ruxolitinib for patients with myelofibrosis.

Rami Komrokji, MD: Let’s talk about our treatment options and, hopefully, upcoming options. Ruxolitinib has been the standard of care for many of those patients, particularly for those symptomatic for many years. Jamile, can you summarize the experience that we’ve developed with that?

Jamile Shammo, MD, FACP, FASCP: Ruxolitinib has been transformative. There were 2 clinical trials that evaluated intermediate-2 and high-risk patients with MF [myelofibrosis] in a phase 3 prospective randomized setting. COMFORT-I (NCT00952289) took place in the United States. It was a double-blind, randomized study that compared ruxolitinib with best available therapies. The dosing was dependent on the platelet count. Patients with a platelet count between 100,000 and 200,000 per mm3 received 50 mg twice a day, and anyone above 200,000 per mm3 received 20 mg twice a day. The primary end point of that study was 35% or greater reduction in spleen volume plus a reduction in total symptom score at 24 weeks.

The net outcomes of this study and COMFORT-II (NCT00934544) were presented in various congresses. The difference was statistically significant. COMFORT-II looked very similar, in that it was open label and it looked at spleen volume reduction. At week 48, the response rate was 28%, which is slightly lower than what was seen in COMFORT-I but nevertheless statistically significant compared with best available therapy. It was transformative because we had a treatment that improved patients’ quality of life and reduced spleen size. It had adverse effects in terms of cytopenias, but they were managed by dose reductions. Unfortunately, it isn’t a curative treatment, so at some point there would be progression.

At this year’s ASCO [American Society of Clinical Oncology Annual Meeting], there was an abstract issue from [The University of Texas] MD Anderson [Cancer Center] that talked about a subset of patients that had been on this agent for more than 3 years. They looked at 130 patients who had been on this drug for over 3 years. It’s the lucky group. All of us have those patients. It turns out that about 40% of those people had been on this agent for over 10 years, which is remarkable. In a multivariate analysis, age and neutropenia were the only influencers as to why they would come off this drug. It’s a very good option for patients who have this disorder. We need to keep an eye on things like opportunistic infections—herpes zoster is one such issue—and cytopenias, which can be managed. The only other piece is platelet count cutoff, which was employed in the clinical trial.

Transcript edited for clarity.

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