NCCN myelofibrosis guideline: Patient voice is key
EXPERT ANALYSIS AT THE NCCN ANNUAL CONFERENCE
COMFORT-1 update: ruxolitinib responses durable in myelofibrosis
To date, ruxolitinib is the only Food and Drug Administration–approved drug for the treatment of myelofibrosis.
The randomized controlled phase III COMFORT I and II trials conducted in the United States and Europe, respectively, demonstrated that the oral JAK1/JAK2 inhibitor has a rapid, beneficial impact on both survival and disease-associated enlargement of the spleen and improvement in related symptoms, Dr. Mesa said.
A 5-year update on data from 309 patients in the COMFORT-1 trial, as reported at the annual meeting of the American Society of Clinical Oncology in 2016, confirmed the durability of treatment responses to ruxolitinib in patients initially randomized to receive the drug, he said.
“We were able to demonstrate a continued survival advantage for those individuals receiving ruxolitinib,” he added.
At weeks 24 and 264, the mean spleen volume reduction was 31.6% and 37.6%, respectively, in those originally randomized to ruxolitinib. The median duration of at least 35% spleen volume reduction was 168.3 weeks.
Overall survival favored ruxolitinib (hazard ratio, 0.69). Median overall survival in the ruxolitinib group had not yet been reached.
“But we realize our work is not done. The survival curve does not plateau; we are not curing these patients. We’re having meaningful impact, but we have room to continue to improve,” he said.
Also, there is an initial drop in platelet counts that tends to stabilize, but not improve, and there is worsening of anemia (new onset grade 3 or 4 anemia was 25.2% with ruxolitinib, and 26.1% in 111 of 154 patients who crossed over from the placebo group), and although this tends to improve, these are among areas of unmet need, he added.
Further, long-term risks of treatment include cutaneous malignancies (basal cell carcinoma occurred in 7.7% and 9.0% of treatment and crossover patients, respectively), which are difficult to separate from baseline hydroxyurea use, and increased risk of herpes zoster (which occurred in 10.3% and 13.5% of treated and crossover patients).
However, there appears to be no increased risk – and there may be a slight decreased risk – of progression to acute leukemia, Dr. Mesa said.
Dr. Mesa disclosed that he has received consulting fees, honoraria, and/or grant/research support from ARIAD Pharmaceuticals, Celgene, CTI BioPharma, Galena Biopharma, Gilead Sciences, Incyte, Novartis Pharmaceuticals, and Promedior.
