P1041: IMPACT OF FEDRATINIB ON SPLEEN VOLUME AND MYELOFIBROSIS SYMPTOMS IN PATIENTS WITH SUBSTANTIAL SPLENOMEGALY: POST HOC ANALYSES FROM THE JAKARTA AND JAKARTA2 TRIALS

Abstract

Background: In myelofibrosis (MF), splenomegaly is a marker of disease progression, and larger spleen size (SS) is correlated with poorer survival and debilitating symptoms. Fedratinib (FEDR) is an oral, selective Janus kinase 2 (JAK2) inhibitor approved as first-line (1L) treatment (Tx) of patients (pts) with MF and in pts previously treated with ruxolitinib (RUX). In the phase 3, placebo-controlled JAKARTA trial (NCT01437787) and the phase 2, single-arm JAKARTA2 trial (NCT01523171), pts experienced substantial improvements in spleen volume and MF symptoms after receiving 6 FEDR Tx cycles. Given the prognostic impact of splenomegaly, these analyses explore whether these clinical benefits were influenced by pre-Tx SS. Aims: Investigate the efficacy of FEDR 400 mg/d in JAKARTA and JAKARTA2, in pt subgroups defined by baseline (BL) SS. Methods: The JAKARTA trial assessed FEDR 400 mg/d, FEDR 500 mg/d, and placebo in pts with JAK inhibitor-naïve MF, and the JAKARTA2 trial evaluated FEDR 400 mg/d (starting dose) in pts resistant/intolerant to prior RUX. Both studies enrolled pts with intermediate- or high-risk MF, SS >5 cm from the left costal margin by palpation, platelets ≥50×109/L, and ECOG PS ≤2. These post hoc analyses included pts from both studies who were allocated to receive FEDR 400 mg/d (the approved dosage) in continuous 28-d Tx cycles. Pt subgroups were divided according to BL median SS (mSS) in each trial. Changes from BL in spleen volume and Myelofibrosis Symptom Assessment Form (MFSAF) total symptom score (TSS) were measured at the end of cycle 6 (EOC6). Spleen volume was assessed by MRI/CT scan; MFSAF TSS was the sum of 6 MF symptom scores: night sweats, early satiety, pruritus, pain under ribs-left side, abdominal discomfort, and bone/muscle pain. Eligible pts must have had spleen volume and/or TSS data at BL and EOC6. Results: Overall, 96 pts in JAKARTA and 97 pts in JAKARTA2 received FEDR 400 mg/d; mSS (range) at BL was 16 (5–40) cm and 18 (5–36) cm, respectively. In the JAKARTA <mSS and ≥mSS cohorts, median BL spleen volume was 1771 (316–3396) mL and 3329 (983–6430) mL, respectively, and median TSS was 13.0 (0.0–54.9) and 17.2 (0.4–57.0). In JAKARTA2, median BL spleen volume was 1937 (737–4305) mL and 4002 (1821–7815) mL for pts with <mSS and ≥mSS, respectively; BL TSS was 17.2 (0.7–48.0) and 23.6 (1.0–44.0). Overall, 75 (78%) pts in JAKARTA and 51 (53%) pts in JAKARTA2 had spleen volume data available at BL and EOC6; the <mSS and ≥mSS cohorts, comprised 37 and 38 pts, respectively, in JAKARTA, and 31 and 20 pts in JAKARTA2. Median spleen volume reduction (SVR) from BL was similar between the <mSS and ≥mSS cohorts in each trial, and 97% of pts with ≥mSS in both trials achieved some degree of SVR. In JAKARTA, median SVR at EOC6 was −38% (95% CI, −43 to −31) in the <mSS and −40% (95% CI, −40 to −28) in the ≥mSS cohort; in JAKARTA2, median SVR was −37 (95% CI, −43 to −30) in the <mSS and −38.5% (95% CI, −49 to −14) in the ≥mSS cohort. TSS data were available at BL and EOC6 for 71 (74%) pts in JAKARTA and 51 (53%) pts in JAKARTA2. Changes from BL in TSS at EOC6 were similar in the JAKARTA <mSS and ≥mSS cohorts, with median TSS reductions of −49% and −51%, respectively. Median TSS changes at EOC6 in JAKARTA2 were greater for pts with larger spleens, −36% and −49% in the <mSS and ≥mSS cohorts, respectively. Image:Summary/Conclusion: Pts who completed 6 Tx cycles with FEDR 400 mg/d, whether used as 1L MF Tx or after RUX Tx, experienced substantial improvements in spleen volume and MF symptom severity regardless of the extent of splenomegaly at BL.