Orlando, Florida—According to updated study results presented at the 2019 ASH Annual Meeting, combination therapy comprising ruxolitinib and pomalidomide is feasible for use in patients with poor-risk myelofibrosis (MF) and anemia.

“Anemia remains one cardinal symptom associated with reduced quality of life (QoL) in patients with MF which is normally not being addressed by ruxolitinib. In our previous MPNSG-0109 trial, single-agent pomalidomide improved cytopenia in 14% (pomalidomide 0.5 mg QD) and 29% (pomalidomide 2.0 mg QD) of MF patients, respectively,” explained Frank Stegelmann, MD, Department of Internal Medicine III, University Hospital of Ulm, Germany, and colleagues.

Thus, Dr Stegelmann et al began the multi-center, open-label MPNSG-0212 clinical trial (N = 90) to evaluate whether or not combining ruxolitinib with pomalidomide could improve anemia and QoL in patients with MF.

Patients were included in the study if they had MF and anemia (hemoglobin [Hb] <10 g/dL and/or red blood cell transfusion independence [RBC-TI]), and excluded if they were eligible for allogeneic transplantation or had low platelet counts (<100/nL).

A total of 40 patients were given ruxolitinib 10 mg twice daily plus low-dose pomalidomide 0.5 mg once daily (cohort 1) and 50 patients received a step-wise increase of pomalidomide from 0.5 mg to 1 mg and 2 mg once daily after receiving 3 and 6 cycles spanning 28 days, respectively (cohort 2).

The primary end points of the ongoing MPNSG-0212 study are safety, anemia response after 12 cycles, and clinical benefit. The investigators defined clinical benefit as stable disease plus Hb increase ≥1 g/dL in patients with RBC-TI or doubling of RBC transfusion intervals, and/or significant (>25%) QoL improvement.

As of May 31, 2019 (the point of data cutoff), there were 79 patients included in the study, 67 of whom had data available for assessment (ie, 40 patients from cohort 1 and 21 patients from cohort 2).

At baseline, patients in the study had a median age of 72 years; 53% had received prior therapy (22%, ruxolitinib and 4%, pomalidomide); the median Hb level was 8.6 g/dL; and 28% had RBC transfusion dependence. Until data cutoff, the median number of treatment cycles were 12 and 11 in cohorts 1 and 2, respectively.

Overall, Dr Stegelmann and colleagues documented the occurrence of 502 adverse events (AE), primarily grade 1/2. Fatigue, diarrhea, and muscle cramps were the most common grade 1/2 AEs occurring in >20% of patients. There were a total of 87 serious AEs recorded, the most common (≥3 patients) being pneumonia, leukemic transformation, worsening of general condition, central nervous system ischemia, and sepsis.

Notably, the incidence or severity of serious AEs was not increased in cohort 2. Only 11 (27%) and 3 (11%) patients in cohorts 1 and 2, respectively, had to have their treatment with ruxolitinib and/or pomalidomide interrupted, and 2 patients halted treatment permanently because of hematotoxicity.

The majority of patients were able to increase their pomalidomide dose to 1 mg and 2 mg once daily after 3 and 6 cycles, respectively.

Ultimately, 28 (42%) patients received therapy for >12 cycles, 16 (24%) for >24 cycles, and 3 (4%) for >60 cycles because of sustained response or clinical benefit. Between baseline and the end of cycle 18, the mean Hb rate notably increased from 8.7 g/dL to 9.6 g/dL, with stability sustained thereafter.

“Combination treatment using ruxolitinib plus pomalidomide is feasible in patients with poor-risk MF and resulted in an objective anemia response rate of 18% in cohort 1,” Dr Stegelmann and colleagues said.

“Of note, 42% of patients were treated with >12 cycles and showed a longer lasting stabilization of their disease with sustained improvement of Hb and QoL. Step-wise increase of the pomalidomide dose in cohort 2 is safe and feasible with 70% of patients still on study treatment,” they concluded.—Hina Porcelli

Stegelmann F, Koschmiede S, Isfort S, et al. Updated Results from the German Mpnsg-0212 Combination Trial: Ruxolitinib Plus Pomalidomide in Myelofibrosis with Anemia. Presented at: the 2019 ASH Annual Meeting & Exposition; December 7-10, 2019; Orlando, FL. Abstract 672.