Introduction: Anemia is a sign of disease progression and a key prognostic factor in myelofibrosis (MF). In the phase 3 COMFORT studies, ruxolitinib, a Janus kinase (JAK) 1/JAK2 inhibitor, demonstrated improved overall survival compared with placebo and best available therapy in patients with intermediate 2 or high-risk MF (per the International Prognostic Scoring System [IPSS]). Ruxolitinib treatment was associated with dose-dependent increases in cytopenias that occurred mostly in the first 12 weeks of therapy and were manageable with dose adjustments and red blood cell (RBC) transfusions. The objective of this analysis was to evaluate the differential impact of disease-related anemia (anemia at baseline) and anemia occurring after initiation of ruxolitinib therapy on overall survival (OS) in patients with MF.

Methods: Data from the COMFORT-I and COMFORT-II 3-year data cuts were pooled for this exploratory analysis for patients who survived at least 12 weeks after day 1. Baseline anemia was defined as hemoglobin (Hgb) < 10 g/dL at baseline or receipt of RBC transfusions within 12 weeks prior to day 1. Postbaseline anemia was defined as new or worsening anemia within the first 12 weeks after initiation of ruxolitinib therapy that was grade ≥ 2 (per Common Terminology Criteria for Adverse Events v3.0) and a higher grade than at baseline; this time frame captures 85% of these events during ruxolitinib treatment. Patients were assessed for OS using a cox model stratified by study and baseline anemia status to evaluate the impact of anemia occurring after ruxolitinib initiation on OS.

Results: Among patients treated with ruxolitinib (n = 296), 162 patients were not anemic at baseline and 134 patients were anemic at baseline. Of the 162 patients who were not anemic at baseline, 99 had postbaseline anemia; of the 134 with anemia at baseline, 93 also had postbaseline anemia. Consistent with published prognostic models, anemia at study baseline was prognostic of decreased survival in this study (Figure 1). A higher proportion of those who were anemic at baseline had PMF (58% vs 40%) and high-risk disease per the IPSS (69% vs 40%) vs those who were not anemic at baseline. As expected, mean platelet count (308.3 × 109/L vs 280.5 × 109/L), Hgb (12.2g/dL vs 9.1 g/dL), and leukocyte count (24.2 × 109/L vs 17.0 × 109/L) were higher among patients who were not anemic at baseline vs those who were. Within the subgroups of patients with and without baseline anemia, postbaseline anemia did not impact OS during ruxolitinib therapy (Figure 1) (overall hazard ratio for no postbaseline anemia vs postbaseline anemia = 1.030; 95% CI: 0.615-1.725). Patients treated with ruxolitinib had improved OS compared to control patients, both among those with anemia and without anemia at baseline (Figure 1) (overall hazard ratio for ruxolitinib vs control = 0.644; 95% CI: 0.459-0.903; P = .0102). OS probability at 3 years for ruxolitinib vs control was 0.66 vs 0.57 among patients with anemia at baseline, and 0.87 vs 0.66 among patients without anemia at baseline.

Conclusions: Consistent with validated prognostic models, baseline anemia was associated with decreased OS in the COMFORT studies. Treatment with ruxolitinib improved OS as compared with the control arm regardless of baseline anemia status. Notably, postbaseline anemia that occurred on ruxolitinib therapy did not impact OS and was manageable with dose adjustments and RBC transfusions. We conclude that early onset ruxolitinib-related anemia does not have the same deleterious effect as disease-related anemia.

Figure 1.

Overall survival based on baseline and postbaseline anemia status and treatment received in the COMFORT studies. Rux, ruxolitinib; TI, therapy initiation.

Figure 1.

Overall survival based on baseline and postbaseline anemia status and treatment received in the COMFORT studies. Rux, ruxolitinib; TI, therapy initiation.


Gupta:Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Honoraria, Research Funding. Harrison:Gilead: Honoraria; Shire: Speakers Bureau; Sanofi: Honoraria, Speakers Bureau; Novartis: Honoraria, Research Funding, Speakers Bureau; CTI Biopharma: Consultancy, Honoraria, Speakers Bureau. Al-Ali:Celgene: Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding. Foltz:Promedior: Research Funding; Novartis: Honoraria, Research Funding; Gilead: Research Funding. Montgomery:Incyte: Employment. Peng:Incyte Corporation: Employment, Equity Ownership. Gopalakrishna:Novartis Pharma AG: Employment. Verstovsek:Incyte Corporation: Research Funding; Astrazeneca: Research Funding; Lilly Oncology: Research Funding; Roche: Research Funding; Geron: Research Funding; NS Pharma: Research Funding; Bristol Myers Squibb: Research Funding; Gilead: Research Funding; Celgene: Research Funding; Seattle Genetics: Research Funding; Promedior: Research Funding; CTI BioPharma Corp.(formerly Cell Therapeutics, Inc.): Research Funding; Galena BioPharma: Research Funding; Pfizer: Research Funding.

Author notes


Asterisk with author names denotes non-ASH members.