Orlando, Florida—Long-term analyses of the MEDALIST study show sustained responses with durable clinical benefit in patients with myelodysplastic syndromes (MDS) receiving luspatercept for anemia, superior to that of patients receiving placebo.

“In the phase 3, randomized, double-blind, placebo-controlled MEDALIST study…, luspatercept significantly reduced transfusion burden vs placebo,” explained Pierre Fenaux, MD, PhD, Service d’Hématologie Séniors, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris, France, and colleagues, who presented longer-term efficacy analyses, including multiple responses, and safety at the 2019 ASH Annual Meeting.

On the MEDALIST study, patients ≥18 years of age with IPSS-R-defined Very low-, Low-, or Intermediate-risk MDS with ring sideroblasts were randomized 2:1 to receive luspatercept or placebo subcutaneously every 3 weeks.

This analysis assessed the achievement and number of individual response periods of red blood cell transfusion independence ≥8 weeks, along with clinical benefit, defined as achieving red blood cell transfusion independence ≥8 weeks and/or modified hematologic improvement-erythroid response per International Working Group 2006 criteria, and total duration of clinical benefit. Longer-term efficacy and safety were also evaluated.

8-week red blood cell transfusion burden was assessed in patients in the 16 weeks before study randomization: 2 to <4 U red blood cells (n=66; 30.1% and 26.3% of patients receiving luspatercept and placebo, respectively), ≥4 to <6 U (n=64; 26.8% and 30.2%, respectively), and ≥6 U (n=99; 43.1% and 43.4%, respectively). Both the luspatercept and placebo arms had a median baseline burden of 5 red blood cell transfusions in 8 weeks.

As of January 7, 2019, 72 (47.1%) pts treated with luspatercept and 12 (15.8%) treated with placebo achieved red blood cell transfusion independence ≥8 weeks. In luspatercept responders, analysis of multiple response periods of red blood cell transfusion independence ≥8 weeks demonstrated that 48 (66.7%) pts had ≥2 separate response periods, 22 (30.6%) had ≥3, 12 (16.7%) had ≥4, and 7 (9.7%) had ≥5.

Additionally, of the 12 patients achieving red blood cell transfusion independence ≥8 weeks with placebo, 4 (33.3%) had ≥2 responses. No patients receiving placebo had >3 responses.

A total of 48 patients receiving luspatercept remained on treatment as of January 7, 2019. No patients receiving placebo remained on treatment. The median treatment duration was 50.9 (range 5.9–147.0) weeks in patients receiving luspatercept compared to 24 (range 7.4–103.0) weeks in those receiving placebo.

The median duration of the longest period of red blood cell transfusion independence ≥8 weeks during weeks 1–48 was 30.6 weeks with luspatercept and 18.6 weeks with placebo. The median total duration of clinical benefit was 83.6 and 26.8 weeks for those responding to luspatercept (n=97) and placebo (n=20), respectively.

Additionally, of the 97 patients treated with luspatercept evaluable for clinical benefit, the median duration of clinical benefit in those with baseline transfusion burden of 4 to < 6 U/8 weeks was 87.9 (range 13–125) weeks, of < 4 U/8 weeks was 84.7 (range 21–147) weeks, and of ≥ 6 U/8 weeks was 64.9 (range 8–122) weeks.

Dr Fenaux and colleagues noted that 12 patients treated with luspatercept did not require a transfusion after the first dose up to week 48 or until time of analysis. As of the January 7, 2019 data cutoff, 3 (25%) of these patients maintained their response.

Adverse events (AEs) occurred more frequently in patients receiving luspatercept than placebo and included fatigue, diarrhea, asthenia, and dizziness. Adverse events occurred early on (cycles 1-4), were mainly grad 1 or 2, decreased over time, and were not associated with a higher dose level. Progression to acute myeloid leukemia was similar in those receiving luspatercept (n=3 [2%]) and placebo (n=1 [1.3%]).

“Most LR-MDS patients achieving RBC-TI [red blood cell transfusion independence] and/or HI-E [hematologic improvement-erythroid] with luspatercept in the MEDALIST study had multiple responses with durable clinical benefit superior to that of patients receiving placebo, including those with a high baseline transfusion burden,” Dr Fenaux and colleagues concluded.—Janelle Bradley

Fenaux P, Mufti GJ, Buckstein RJ, et al. Assessment of Longer-Term Efficacy and Safety in the Phase 3, Randomized, Double-Blind, Placebo-Controlled MEDALIST Trial of Luspatercept to Treat Anemia in Patients (Pts) with Revised International Prognostic Scoring System (IPSS-R) Very Low-, Low-, or Intermediate-Risk Myelodysplastic Syndromes (MDS) with Ring Sideroblasts (RS) Who Require Red Blood Cell (RBC) Transfusions. Presented at: the 2019 ASH Annual Meeting & Exposition; December 7-10, 2019; Orlando, FL. Abstract 841.