Pomalidomide Does Not Significantly Improve RBC Transfusion Needs in Myelofibrosis

Anemia occurs commonly in patients with myeloproliferative neoplasm (MPN)-associated myelofibrosis (MF), and such patients are often red blood cell (RBC) transfusion-dependent. No therapy approved by the U.S. Food and Drug Administration is particularly effective at treating MF-associated anemia.

In a study published in Leukemia, Ayalew Tefferi, MD, from the Division of Hematology in the Department of Internal Medicine at the Mayo Clinic College of Medicine in Rochester, Minnesota, and co-authors examined whether treatment with the immune-modulating drug pomalidomide could increase the proportion of patients achieving RBC transfusion independence, compared with placebo.

Results from previous trials comparing different doses of pomalidomide (2.0 or 0.5 mg/day), with or without prednisone, in this setting suggested that a lower dose of pomalidomide alone was associated with a high platelet response rate, prompting Dr. Tefferi and colleagues to confirm response rates with pomalidomide 0.5 mg in this multicenter, randomized, double-blind, parallel-group, placebo-controlled phase III study.

The trial enrolled 229 adult patients (median age = 70 years; range = 40-90 years) with MPN-associated MF, including primary MF (75%; n=172), post-polycythemia vera MF (11%; n=25), and post-essential thrombocythemia MF (14%; n=34), between September 2010 and August 2012. All patients were RBC transfusion-dependent (defined as an average RBC transfusion frequency of ≥2 U/28 days over ≥84 days immediately prior to randomization, with no interval of >42 days without ≥1 RBC transfusion) and had a hemoglobin concentration ≤13.0 g/dL at randomization. Patients were excluded if they had received RBC transfusions because of bleeding or chemotherapy- or radiation-induced anemia or if they had received thalidomide, lenalidomide, bone marrow suppressants, or any investigational drug within 1 month of randomization.

…We conclude no efficacy of pomalidomide in reversing RBC transfusion dependence.

Patients were randomized 2:1 to receive oral pomalidomide 0.5 mg/day (n=152) or placebo (n=77).

The authors found that the rates of transfusion independence were similar between pomalidomide and placebo (16% [95% CI 11-23] vs. 16% [95% CI 8-26]; p=0.87).

The median time to response was similar in the pomalidomide cohort than in the placebo cohort (7 weeks [range = 0-20 weeks] vs. 2 weeks [range = 0-15 weeks]; p=0.22).

Median durations of response in the pomalidomide and placebo groups were not reached and 5.5 months, respectively, and this difference was not statistically significant (p=0.44). The authors added that, of the 25 patients who responded to pomalidomide, 12 had a response duration of >186 days, compared with one of the 12 responders in the placebo group.

“Based on these data, we conclude no efficacy of pomalidomide in reversing RBC transfusion dependence,” Dr. Tefferi and co-authors wrote. They proposed that the pomalidomide responses were “spontaneous reversals of RBC transfusion dependence” that occurred at similar rates to those in the placebo cohort, and could potentially explain the similar response rates between the groups. “We were, therefore, surprised to find several differences in variables associated with response between the cohorts,” they added.

Outcomes were analyzed according to age (≤65 vs. >65 years), white blood cell (WBC) count (<25 vs. ≥25×109/L), and the intensity of RBC transfusion dependence prior to randomization (≤4 vs. >4 U/28 days over the preceding 84 days).

In the pomalidomide cohort, responses were non-significantly associated with:

  • transfusion dependence ≤4 U RBC/28 days (odds ratio [OR] = 3.1; 95% CI 0.9-11.1; p=0.09)
  • age ≤65 years old (OR=2.3; 95% CI 0.9-5.5; p=0.07)
  • type of MPN-associated MF (OR=2.6; 95% CI 0.7-9.5; p=0.14)

Meanwhile, responses in the placebo cohort were variably associated with:

  • transfusion dependence ≤4 U RBC/28 days (OR=8.6; 95% CI 0.9-82.3; p=0.06)
  • WBC count ≥25×109/L at randomization (OR=4.9; 95% CI 0.8-28.9; p=0.08)
  • interval from diagnosis to randomization of >2 years (OR=4.9; 95% CI 1.1-21.9; p=0.04)

The most common treatment-related adverse events (AEs) were peripheral edema, fatigue, pyrexia, and diarrhea, and peripheral edema and neutropenia were significantly more common in the pomalidomide group. The most common grade ≥3 AEs were neutropenia, thrombocytopenia, anemia, and pneumonia.

Dr. Tefferi and colleagues noted several potential limitations of the study, including the use of transfusion-independence response criteria that were more stringent than recent criteria published by the International Working Group for MPN Research and Treatment. “The criteria we used do not reflect the clinical benefit physicians expect, wherein a >50 percent reduction in RBC transfusion intensity may be considered beneficial depending on the baseline intensity,” the authors wrote. “Consequently, the strength of our conclusion of no efficacy should be downgraded according to the [Grading of Recommendations Assessment, Development and Evaluation] criteria.”


Tefferi A, Al-Ali HK, Barosi G, et al. A randomized study of pomalidomide vs placebo in persons with myeloproliferative neoplasm-associated myelofibrosis and RBC-transfusion dependence. Leukemia. 2017;31:896-902.