Continued Luspatercept Therapy Benefits Patients with Lower-Risk MDS

There was an “improved benefit” from continued luspatercept therapy in patients who had lower-risk myelodysplastic syndromes (MDS) with ring sideroblasts, according to a post hoc subanalysis of the MEDALIST trial.

Luspatercept is a first in-class recombinant fusion protein and a hypothesized alternative treatment to red blood cell (RBC) transfusions, as it could eliminate or reduce the need for the procedure.

Patients with lower-risk MDS who receive luspatercept may see improvement in their overall health-related quality of life, according to the study’ investigators, led by Ulrich Germing, MD, of Heinrich-Heine University in Düsseldorf, Germany.

The investigators performed the subanalysis “to understand how luspatercept may reduce RBC transfusion burden relative to the patient’s level of transfusion burden before initiation of treatment.”

Dr. Germing and colleagues noted that the clinical benefits of luspatercept are “not well understood and would be relevant to clinicians to help guide treatment decision-making.”

The MEDALIST trial randomized adult patients who had lower-risk MDS with ring sideroblasts and a history of regular RBC transfusions to receive luspatercept 1.0 mg/kg or placebo every three weeks. The luspatercept dose could be adjusted up to 1.75 mg/kg. The primary efficacy endpoint was RBC transfusion independence for eight weeks during the primary treatment phase. The primary treatment phase occurred from weeks one to 24, with an evaluation conducted at week 25.

Patients who showed clinical benefit and no disease progression, as assessed by investigators, could continue to receive luspatercept or placebo in a double-blind treatment extension phase until they showed no clinical benefit, had disease progression, experienced unacceptable side effects, or withdrew from the study. The extension phase continued with three-week cycles.

This post hoc subanalysis evaluated the effect of luspatercept on cumulative RBC transfusion units and visits over time based on pretreatment transfusion burden levels. It also evaluated the benefits of continuing luspatercept treatment beyond week 25 in patients who did not achieve RBC transfusion independence for eight weeks or more during the first 24 weeks of the trial.

The results showed fewer RBC transfusion units and visits in patients who received luspatercept compared to placebo through week 25 and through 144 weeks of treatment, especially in patients with low baseline transfusion burden.

Of the patients who did not have a response at week 25 but continued treatment, most received the maximum dose of luspatercept and 16% achieved RBC transfusion independence for eight weeks or more during week 25 through week 48, with 26% reducing RBC transfusion burden, 10% achieving an erythroid response, 44% reducing serum ferritin, and an average increase in hemoglobin of 1.3 g/dL from baseline.

“These data have implications for clinical practice, as transfusion units and visits are less in luspatercept-treated patients through week 25 regardless of baseline transfusion burden, and continuing luspatercept beyond week 25 can potentially provide additional clinical benefits for initial nonresponders,” the authors wrote.

Reference

Germing U, Fenaux P, Platzbecker U, et al. Improved benefit of continuing luspatercept therapy: sub-analysis of patients with lower-risk MDS in the MEDALIST study. Ann Hematol. 2023;102(2):311-321. doi:10.1007/s00277-022-05071-8