Ruxolitinib plus pomalidomide in myelofibrosis with anemia: results from the MPNSG-0212 combination trial (NCT01644110)

Background: Anemia is one clinically relevant symptom in patients (pts) with myelofibrosis (MF) which is not being addressed by treatment with ruxolitinib (RUX). Single treatment with pomalidomide (POM) improved cytopenia in 14% (POM 0.5 mg QD) and 29% (POM 2 mg QD) of MF pts in our previous MPNSG‐0109 trial. Aims: Therefore, we sought to investigate the combination of RUX plus POM in MF with anemia. Methods: MPNSG‐0212 (NCT01644110) is a multicenter, open‐label, single‐arm phase‐Ib/II trial with a target population of 90 pts in a two‐stage design. Pts 1–40 (cohort 1 [co1]) are treated with RUX (10 mg BID) plus low‐dose POM (0.5 mg QD), while pts 41–90 (cohort 2 [co2]) receive a step‐wise dose increase of POM after 3 and 6 cycles (0.5 ‐> 1 ‐> 2 mg QD). Primary endpoints are safety of the combination therapy and anemia response after 12 28‐day cycles (according to IWG‐MRT and RBC transfusion independency [RBC‐TI] criteria). Main inclusion criterion is MF with anemia (Hb <10 g/dL and/or RBC‐TD). Pts suitable for allogeneic transplantation and pts with low platelets (<100/nL) are excluded. Results: Data from 59 pts were available for this analysis. Baseline characteristics were as following: Median age 72 yrs (range 49–84), 53% had prior treatment (RUX in 22%, POM in 4%), median Hb level was 8.5 g/dL (range 5.4–11.7), 27% fulfilled the RBC‐TD criterion, median spleen size was 17.8 cm (range 12.6–36), 80% had constitutional symptoms, 93% were intermediate‐2 (64%) or high‐risk (29%) according to DIPSS, and 55% had ≥1 high molecular risk mutation ( ASXL1, SRSF2, EZH2, and/or IDH1/2 ). Median number of treatment cycles was 12 (range 2–59) in co1 and 11 (range 1–16) in co2. 414 adverse events (AE) were recorded (mostly °I/II). Number or severity of AE were not increased in co2. Most common AE (°I/II) were anemia (34% of pts) and fatigue (29%) in the first weeks of treatment as well as musculoskeletal cramps (25%). Regarding serious AE (SAE), n = 77 were recorded in 64% of pts. No fatal (S)AE occurred in co2. Most common SAE were pneumonia (12%), leukemic transformation (10%), and worsening of general condition (7%). Interruption/termination of RUX and/or POM was rare in co1 and co2. In co1, 18/40 pts (45%) continued treatment beyond cycle 12 because of objective anemia response (7/40, 18%: CI‐Hb [Hb increase ≥2 g/dL] n = 5, PR and RBC‐TI n = 1 each) or stable disease in combination with clinical benefit (CB, 11/40, 28%) defined as: Hb increase ≥1 g/dL and/or doubling of RBC transfusion intervals [n = 4] or improvement of fatigue and/or overall quality of life >25% according to MPN‐SAF [n = 7]. Notably, 16 pts of co1 (40%) were on treatment for more than 24 cycles, and mean Hb increased continuously from 8.7 g/dl at baseline to 9.8 g/dL at end of cycle 18 and sustained thereafter at 9.7 g/dL until end of cycle 30 (Figure 1). In co2, 6/19 pts (31%) reached cycle 12 and continued treatment afterwards: 1/6 (17%) experienced RBC‐TI, whereas 5 had CB; 16/19 pts (84%) were still on treatment at the time of the analysis with 10/16 pts (62%) not having reached cycle 12 yet. Increase of the POM dose to 1 mg QD after 3 cycles and 2 mg QD after 6 cycles was feasible in 94% and 69% of pts, respectively. Summary/Conclusion: Combination treatment of RUX and POM is safe and feasible in pts with poor‐risk MF and resulted in an objective anemia response rate of 18% with RUX plus low‐dose POM in co1. Notably, 40% of pts showed a long‐lasting stabilization of their disease with sustained improvement of Hb and quality of life. Updated results on more than 70 pts will be presented. image