PS1465 SAFETY AND EFFICACY OF RUXOLITINIB (RUX) IN PATIENTS WITH MYELOFIBROSIS (MF) AND ANEMIA (HB <10 G/DL): RESULTS AT WEEK (WK) 24 OF THE REALISE TRIAL
Authors: Cervantes F. , Gisslinger H. , Radinoff A. , Passamonti F. , Foltz L. , Ross D.M. , Vianelli N. , Mannelli F. , Zachee P. , Myasnikov A. , Zor E. , Gilotti G. , Tiwari R. , Al‐Ali H.K. 
Published: June 2019

Background:RUX is the only approved JAK inhibitor for the treatment of disease‐related splenomegaly or symptoms in adults with MF. Dose‐dependent anemia has been observed with RUX, generally in the first 12 wks of treatment and is managed with dose adjustments and/or blood transfusions. Current label starting doses in MF are 5, 15, or 20 mg BID depending on platelet count (≥50 to <100 × 109/L, 100 to 200 × 109/L, >200 × 109/L, respectively), regardless of baseline Hb level.Aims:To evaluate safety and efficacy of an alternative RUX dosing regimen in pts with MF and anemia (Hb <10 g/dL): a starting dose of 10 mg BID for 12 wks and gradual up‐titration.Methods:A multicenter, phase II, open label, single arm study (NCT02966353). Eligible patients (pts) had primary MF, post‐essential thrombocythemia (ET) MF or post‐polycythemia vera (PV) MF, palpable (≥5 cm) spleen, Hb level <10 g/dL and platelet count ≥50x109/L. Pts started RUX at 10 mg BID and, after 12 wks, up titrations to 15 or 20 mg BID were allowed based on efficacy and platelet counts. The primary endpoint was proportion of pts achieving ≥50% reduction in spleen length (SL) at Wk 24. Secondary endpoints included transfusion requirements and dependence over time, safety (AEs), and patient‐reported outcomes.Results:Fifty‐one pts (58.8% male, median age 67 years [45–88 years]) completed 24 wks of follow‐up on treatment or discontinued treatment before data cutoff (24 July 2018). In total, 35 (68.6%) pts had primary MF, 11 (21.6%) had post‐ET MF, and 5 (9.8%) had post‐PV MF. Overall, 37.3, 54.9, and 7.8% of pts had ECOG performance scores of 0, 1, and 2, respectively. Proportions of pts per DIPSS category were: Int‐1 17.6%, Int‐2 54.9%, High 19.6%, unknown 7.8%. Median duration of exposure to RUX was 38.0 wks. At Wk 24, 63.6% (28/44) of pts had ≥50% SL reduction and 11.4% (5/44) had reductions of 25 to 50%. Hb levels dropped in the first 8 wks of treatment (median −6.0 g/L [‐37.0 to +31.6 g/L]), then stabilized; platelet levels remained constant. At data cutoff, 32 pts were still undergoing treatment and 19 had discontinued (pt/guardian decision 13.7%, physician decision 7.8%, trial completion 5.9%, AEs 3.9%, death 3.9%, progressive disease 2.0%). Of 8 transfusion‐dependent (TD; receiving ≥6 units of transfusions 12 wks prior to baseline) pts at baseline, ≥50% SL reduction was seen in 75.0% (6/8) of pts at Wk 24. Of 25 non‐transfusion‐dependent (NTD) pts at baseline, ≥50% SL reduction was seen in 70.8% (17/24) of pts at Wk 24. Eleven pts NTD at baseline became TD. Median dose was 20 mg/day (9–33 mg/day). At Wk 12, 10 pts had dose increases to 15 mg BID as per protocol for patients who have not achieved a 50% reduction in SL. A total of 23 pts had ≥1 dose reduction or interruption most commonly due to AEs (n = 13, of which 10 were hematological). Most common grade 3/4 hematological AEs were anemia (27.5%) and thrombocytopenia (13.7%). The non‐hematological AE occurring in >10% of pts was fatigue (11.8%). At Wk 24, using the MF‐7 Total Symptom Score, 51.1% (23/45) of pts had a ≥50% reduction in total score from baseline. Similarly, 55.6% (25/45) of pts had a ≥50% reduction in Modified MFSAF v2.0 Total Symptom score from baseline.Summary/Conclusion:An alternative dosing regimen of RUX 10 mg BID, with gradual up‐titration after Wk 12, is efficacious in pts with MF and anemia (Hb <10 g/dL), with safety and efficacy results comparable to previous RUX trials. A splenic response was seen at Wk 24 in both TD and NTD pts. These results indicate that treatment‐emergent anemia early after starting RUX does not preclude splenic and symptomatic responses.