MPN-095: Fedratinib Elicits Spleen Volume or Symptom Responses in a Majority of Patients with Intermediate- or High-Risk Myelofibrosis (MF) Treated for 6 Cycles: Results from the JAKARTA and JAKARTA2 Studies

Abstract

Context: MF is characterized by anemia, progressive splenomegaly, and debilitating constitutional symptoms. Fedratinib is a selective JAK2 inhibitor approved in the US for adult patients with intermediate-2 or high-risk MF. Fedratinib was assessed in the phase III, placebo-controlled JAKARTA trial in patients with JAK-inhibitor-naive MF, and in the phase II single-arm JAKARTA2 trial in patients previously treated with ruxolitinib. Reduced splenomegaly and decreased symptom burden are each important goals of treatment but may not occur simultaneously. Objective: Assess the overall clinical benefit of fedratinib, as assessed by proportions of patients in JAKARTA and JAKARTA2 who achieved a spleen volume response, symptom response, or both, after 6 fedratinib treatment cycles. Methods: Both studies enrolled patients with intermediate- or high-risk MF, platelet counts ≥50 × 109/L, and ECOG PS ≤ 2. Efficacy endpoints included rates of spleen volume response (≥35% spleen volume reduction from baseline) and symptom response (≥50% reduction from baseline total symptom score [TSS] on the modified MFSAF) at the end of cycle 6 (EOC6). These analyses assess outcomes among patients in both studies who received fedratinib 400 mg/day and JAKARTA patients randomized to placebo, who had spleen volume and MFSAF TSS data available at baseline and EOC6. Results: In JAKARTA, 67/96 (70%) patients randomized to fedratinib 400 mg and 45/96 (47%) randomized to placebo had spleen volume and MFSAF assessments at baseline and EOC6. Overall, 76% (51/67) of fedratinib-treated patients achieved a spleen volume (n=40 [60%]) or symptom (n=35 [52%]) response, including 24 patients (36%) who achieved both responses. In the placebo arm, 8/45 patients (18%) achieved a spleen volume (n=1) or symptom (n=7) response; no patient attained both responses. In JAKARTA2, 42/97 patients (43%) who received fedratinib 400 mg/day (starting dose) had spleen volume and symptom assessments at baseline and EOC6. Of them, 81% (34/42) achieved a spleen (n=24 [57%]) or symptom response (n=20 [48%]), including 10 patients (24%) who achieved both. Conclusion: A majority of patients with MF who completed 6 fedratinib treatment cycles in JAKARTA or JAKARTA2 experienced a clinical benefit in terms of spleen volume reductions or symptom responses, and one-fourth to one-third of these patients achieved both responses.