Ruxolitinib Results in Better Treatment Response, Less Toxicity in Early Primary Myelofibrosis

For the first time, a study has demonstrated that early primary myelofibrosis (PMF) represents a category of patients who are likely to have better responses and lower toxicities from treatment with ruxolitinib. According to the study, presented at the 60th American Society of Hematology Annual Meeting & Exposition, held December 1-4 in San Diego, California, a World Health Organization (WHO)—defined diagnosis may help better identify patients who may need strict monitoring during treatment with ruxolitinib.

In 2016, WHO criteria labeled early PMF as an individual entity with different clinical and laboratory presentations, as well as a significantly better outcome compared with overt PMF. However, there is a lack of information on the therapeutic effects of ruxolitinib depending on treatment setting.

Aiming to provide data on the differences in baseline clinical and laboratory characteristics, response to treatment, and toxicity between early and overt PMF treated with ruxolitinib, researchers utilized a clinical database in 23 European hematology centers. The database included retrospective data of 537 patients with MF treated with ruxolitinib between January 2011 and July 2018. Spleen and symptoms were documented, and hematologic toxicity and infections were graded.

Of the 199 patients, 59 had a diagnosis of early PMF and 140 had a diagnosis of overt PMF. Median time from diagnosis to ruxolitinib initiation was 22.4 months.

Compared with patients with overt PMF, patients with early PMF started ruxolitinib with higher hemoglobin levels (median, 11.6 vs 10.4 g/dl) and lower circulating blast counts. They were also more frequently at intermediate-1 Dynamic International Prognostic Scoring System risk (69.6% vs 42.5%).The ruxolitinib starting and 12-week titrated doses were comparable between the 2 groups.

At 3 months, 43.1% of patients with early PMF achieved a spleen response, and at 6 months 48.9% achieved a spleen response, compared with 27.9% and 31.3% of patients with overt MF, respectively. The rate of symptom response was also higher among patients with early PMF at both 3 months (82.5% vs 68.8%) and 6 months (90% vs 73.7%).

Toxicities and infections also favored patients with early PMF. In the first 12 months from ruxolitinib initiation, anemia and thrombocytopenia of all grades were observed in 75.6% and 43.1% in patients with overt PMF and in 86.3% and 60% of patients with early and overt PMF, respectively.

At 3 months, anemia was more prevalent among patients with overt PMF (94.7% vs 80%), with 32.6% of these patients having grade 3-4 anemia compared with 17.8% in early PMF. Similarly, rates of thrombocytopenia were also higher among patients with overt PMF at 3 months (51.5% vs 36.2%) and at 6 months (52.9% vs 35.8%), with only 2.2% and 2.5% of patients having grade 3-4 thrombocytopenia, respectively.

During treatment, 75 patients had at least 1 grade 2 or greater infectious episode. Overall, 108 patients discontinued treatment (52.5% of patients with early PMF and 55% of patients with overt PMF). Evolution into acute leukemia occurred in 21 patients.

Overall survival and progression-free survival were comparable between the 2 groups.

Reference

Palandri F, Palumbo G, Abruzzese E, et al. Presentation and outcome of 199 patients with 2016 WHO diagnosis of early and overt primary myelofibrosis treated with ruxolitinib. Proceedings from the American Society of Hematology; December 1-4, 2018; San Diego, CA. Abstract 3052.