Clinical Outcomes in Patients with Myelofibrosis Treated with Ruxolitinib and Anemia-Supporting Medications

Introduction: Patients with myelofibrosis (MF) often present with anemia, and dose-dependent anemia is a known consequence of treatment with the Janus kinase (JAK)1/JAK2 inhibitor ruxolitinib. Current guidelines recommend erythropoiesis-stimulating agents (ESAs) and danazol as options to manage anemia in this population. However, data are lacking regarding the clinical outcomes of patients with MF treated with ruxolitinib and these agents. This post hoc analysis of the phase 3 JUMP trial, the largest ruxolitinib trial to date, evaluated treatment patterns and clinical outcomes of ruxolitinib-treated patients with anemia at study enrollment who initiated treatment with ESAs or danazol.

Methods: The large (N=2233), single-arm, phase 3b, expanded-access JUMP trial evaluated safety and efficacy of ruxolitinib treatment for patients with MF in a setting similar to routine clinical practice. The study included patients ≥18 years old with primary or secondary MF and baseline (BL) platelets ≥50×10⁹/L. Ruxolitinib was administered at a starting dose of 5-20 mg twice daily based on BL platelet count. This post hoc analysis included patients with BL anemia (hemoglobin [Hb] <12.0 g/dL or Hb <10.0 g/dL) who were not receiving supportive care for anemia at enrollment but initiated an ESA or danazol within 3 months of enrollment and remained on that therapy for ≥3 months. Clinical outcomes evaluated were spleen length response (SLR; ≥50% reduction from BL) and symptom response (≥6.5-point increase in Functional Assessment of Cancer Therapy-Lymphoma total score [FACT-Lym TS] from BL).

Results: Of the 1384 patients with Hb<12.0 g/dL (755 with Hb<10.0 g/dL) who were not receiving supportive care for anemia at enrollment, 101 (7.3%) initiated an ESA (n=98) or danazol (n=3) within 3 months of enrollment (52 [6.9%] with Hb<10.0 g/dL) and were included in this analysis. For the Hb<12.0 g/dL cohort, median (range) age was 70 (45-86) years, 54% were male, median (range) MF duration since initial diagnosis was 19 (0.3-312) months, 91% had a palpable spleen, and median (range) time from enrollment to first dose of an ESA or danazol was 43.0 (2-91) days. For the Hb<10.0 g/dL subgroup, median (range) age was 72 (45-85) years, 52% were male, median (range) MF duration since initial diagnosis was 13 (0.3-158) months, 89% had a palpable spleen, and median (range) time from enrollment to first dose of ESA or danazol was 34 (2-90) days.

SLR at Week 12 was achieved by 42 (42%) patients with Hb<12.0 g/dL and 22 (42%) with Hb<10.0 g/dL. SLR at Week 24 was achieved by 34 (34%) patients with Hb<12.0 g/dL and 15 (29%) with Hb<10.0 g/dL. Symptom response at Week 24 was achieved by 26 (26%) patients with Hb<12.0 g/dL and by 12 (23%) with Hb<10.0 g/dL. These rates were similar to those previously reported for the entire JUMP population.

For the Hb<12.0 g/dL cohort, mean (SD) Hb was 9.9 (1.1) g/dL at BL, reached a nadir at Week 4 (8.9 [1.3] g/dL), and steadily increased thereafter to Week 48 (9.9 [1.5] g/dL; mean 1.5% change from BL). A similar trend was observed for the Hb<10.0 g/dL cohort, with mean (SD) Hb 9.1 (0.8) g/dL at BL, a nadir of 8.3 (1.2) g/dL at Week 4, and 9.5 (1.7) g/dL at Week 48 (mean 6.5% change from BL). Evaluable patients with Hb<12.0 g/dL required a mean (SD) 0.8 (0.9) transfusions in the 8 weeks before BL (n=101), 1.3 (1.6) in Weeks 17-24 (n=63), and 0.5 (1.1) in Weeks 41-48 (n=46). Among evaluable patients with Hb<10.0 g/dL, transfusion requirement was mean (SD) 1.0 (1.0) in the 8 weeks before BL (n=52), 1.7 (1.9) in Weeks 17-24 (n=33), and 0.6 (1.3) in Weeks 41-48 (n=25). Mean (SD) ruxolitinib total daily dose was 35 (9) mg at BL for the Hb<12.0 g/dL cohort (34 [9] for the Hb<10.0 g/dL cohort) and for both cohorts decreased to 25 (11) mg through Weeks 45-48.

Conclusions: For patients with anemia at MF diagnosis who received ESA or danazol in combination with ruxolitinib, spleen and symptom responses were similar to those reported in the entire JUMP study population. In addition, most patients tolerated doses of ruxolitinib >25 mg daily and post-enrollment maintained an Hb level within 1.0 g/dL of BL throughout the study period. These results reinforce the use of supportive care for anemia with an ESA or danazol combined with ruxolitinib and may allow for maintenance of ruxolitinib dose intensity in MF patients with anemia.

Vachhani:CTI BioPharma Corp (now Sobi): Consultancy, Research Funding; GlaxoSmith Kline: Consultancy; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Daiichi Sankyo: Consultancy; Abbvie: Consultancy, Research Funding; Astex Pharmaceuticals: Research Funding; Pfizer: Consultancy; GenenTech: Consultancy; Karyopharm: Consultancy; Stemline: Consultancy; MorphoSys: Consultancy; Kartos Therapeutics: Research Funding; Seattle Genetics: Research Funding; Amgen: Consultancy, Research Funding; Takeda: Research Funding; Constellation Pharmaceuticals: Research Funding; Gilead/Forty Seven: Research Funding; Cogent Biosciences: Consultancy; Blueprint Medicines: Consultancy, Research Funding; Novartis: Consultancy. Repp:Incyte Corporation: Current Employment, Current holder of stock options in a privately-held company. Hamer-Maansson:Incyte Corporation: Current Employment, Current holder of stock options in a privately-held company. Braunstein:Incyte Corporation: Current Employment, Current equity holder in publicly-traded company. Bhatt:Incyte Corporation: Current Employment, Current equity holder in publicly-traded company. Al-Ali:Stemline: Honoraria; MSD: Honoraria; Blueprint: Consultancy, Honoraria; Otsuka: Consultancy, Honoraria; AOP: Consultancy, Honoraria; Blueprint: Honoraria; Abbvie: Consultancy, Honoraria, Other: Travel grant; BMS: Consultancy, Research Funding; GSK: Consultancy, Honoraria; Incyte: Research Funding; Novartis: Consultancy, Honoraria; Alexion: Other: Travel grant.