COMFORT-I and -II trials: Post hoc analysis

Currently, ruxolitinib is used for the treatment of patients diagnosed with intermediate- or high-risk myelofibrosis.¹ Results from the phase III COMFORT trials have shown ruxolitinib to reduce spleen volume, improve disease-related symptoms, and prolong overall survival. The COMFORT-I trial compared ruxolitinib therapy with placebo and the COMFORT-II trial compared ruxolitinib with best available treatment.¹

During the European Hematology Association (EHA) 2023 Congress, post hoc analysis results investigating the impact of new or worsening anemia on spleen volume response and total symptom score (TSS) in patients diagnosed with myelofibrosis and treated with ruxolitinib were published.¹ We summarize the key findings below.

Stud design

• Patients were administered ruxolitinib twice daily.
  • 15 mg for patients with a platelet count of 100–200 × 10⁹/L
  • 20 mg for patients with a platelet count >200 × 10⁹/L
• The primary endpoints were:
  • The proportion of patients with a reduction in spleen volume of ≥35% from baseline (SVR35) at Week 24 and Week 48
  • Patients with a ≥50% reduction in TSS at Week 24

Results

• A total of 277 patients were included in the analysis.
  • 55.6% of patients at baseline were nonanemic.
  • 19.9% of patients at baseline were anemic but not transfusion dependent.
  • 24.5% of patients at baseline were anemic and transfusion dependent.
• The percentage of patients achieving SVR35 with new or worsening anemia up to Week 12 according to anemia status and transfusion dependence were similar (Figure 1).

Figure 1. Percentage of patients achieving SVR35 with new or worsening anemia according to anemia status and transfusion dependence* 

NTD, non-transfusion dependent; TD, transfusion dependent; SVR35, spleen volume reduction of ≥35%.
*Adapted from Mauro.¹

• In contrast, a higher percentage of patients who were nonanemic and showed no new or worse anemia up to Week 24 achieved SVR35 compared with patients who were anemic and were either non-transfusion or transfusion dependent (Figure 2).

Figure 2. Percentage of patients achieving SVR35 with no new or worsening anemia according to anemia status and transfusion dependence* 

NTD, non-transfusion dependent; TD, transfusion dependent.
*Adapted from Mauro.¹

• The percentage of patients achieving SVR35 at Week 48 were similar regardless of anemia and transfusion dependence status.
• The proportions of patients with new or worsening anemia up to Week 12 and ≥50% reduction in TSS at Week 24 were:
  • Nonanemic, 51.1%
  • Anemic and non-transfusion dependent, 42.1%
  • Anemic and transfusion dependent, 46.7%
• The proportions of patients with no new or worsening anemia up to Week 12 and ≥50% reduction in TSS at Week 24 were:
  • Nonanemic, 42.9%
  • Anemic and non-transfusion dependent, 40.0%
  • Anemic and transfusion dependent, 54.2%

Conclusion

Patients treated with ruxolitinib experienced decreased spleen volume and improved TSS regardless of anemia and transfusion dependence status. Furthermore, new or worsening anemia after baseline had no effect on the efficacy of ruxolitinib compared with patients who experienced no new or worsening anemia.