San Diego, California—Patients with early primary myelofibrosis (PMF) are likely to have better responses and lower toxicities from ruxolitinib treatment, according to a recent study.

These findings were presented by Francesca Palandri, PhD, MD, Institute of Hematology “L. and A. Seràgnoli,” S. Orsola-Malpighi Bologna University Hospital, Bologna, Italy at the 2018 ASH Annual Meeting.

World Health Organization (WHO) critera identified early PMF as an individual entity with different clinical and laboratory presentations, as well as a significantly better outcome compared with overt PMF. However, little information exists on the therapeutic effects of ruxolitinib in the context of each disease separately.

Based on this, Dr Palandri and colleagues aimed to report the difference between early and overt PMF in patients treated with ruxolitinib in terms of baseline clinical and laboratory characteristics, response to treatment, and toxicity.

A clinical database which included retrospective data on 537 myelofibrosis patients treated with ruxolitinib between January 2011 and July 2018 was created. Spleen and symptom response to ruxolitinib were evaluated and hematologic toxicity and infections were graded.

A total of 199 patients had a diagnosis of early PMF (n=59) or overt PMF (n=140) confirmed by bone marrow biopsy at the start of ruxolitinib therapy and were included in the analysis. The median time from diagnosis to the start of ruxolitinib was 22.4 months.

Patients with early PMF started ruxolitinib with higher hemoglobin levels than those with overt PMF (median, 11.6 vs 10.4 g/dl, p = .01), as well as lower circulating blast counts. Patients with early PMF were also more frequently intermediate-1 Dynamic International Prognostic Scoring System (DIPSS) risk than patients with overt PMF (69.6% vs 42.5%, p<.001).

At 3 and 6 months, 43.1% and 48.9% of patients with early PMF achieved a spleen response compared to 27.9% and 31.3% of patients with overt PMF (p = .04 and p = .04, respectively). Patients with early PMF also had a higher rate of symptom response at 3 (82.5% vs 68.8%, p = .05) and 6 months (90% vs 73.7%, p = .02).

Anemia and thrombocythemia of all grades occurred in 75.6% and 43.1% of patients with early PMF and 86.3% and 60% of patients with overt PMF, respectively.

At 3 months, anemia was more prevalent among patients with overt PMF (94.7%) compared to patients with early PMF (80%), with 32.6% with overt PMF having grade 3-4 anemia compared to 17.8% with 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.

A total of 75 patients reported with at least 1 grade 2 or greater infectious episode during therapy with ruxolitinib.

Overall, 108 patients discontinued ruxolitinib (52.5% with early and 55.0% with overt PMF, p= .7). Evolution into acute leukemia occurred in 21 patients. After a median follow-up of 23 months, 69 patients died, specifically due to disease progression (38%), leukemic transformation (16.9%), infections (11.3%), hemorrhage/thrombosis (12.6%, second neoplasias (8.5%) or transplant-associated toxicity (2.8%).

Overall (p = .88) and progression-free (p = .86) survival were comparable between early and overt patients with PMF.

“This study indicates for the first time that early PMF represents a category of patients that is projected to have better responses and lower toxicities from RUX [ruxolitinib] treatment,” Dr Palandri and colleagues concluded.—Janelle Bradley

Palandri F,  Palumbo GA, Abruzzese E, et al. Presentation and Outcome of 199 Patients with 2016 Who Diagnosis of Early and Overt Primary Myelofibrosis Treated with Ruxolitinib. Presented at: the 60th ASH Annual Meeting and Exposition; December 1-4, 2018; San Diego, CA. Abstract 3052.