KEY TAKEAWAYS
- The phase 3 MEDALIST study of luspatercept evaluated the clinical benefit of luspatercept in achieving red blood cell transfusion independence (RBC-TI) of ≥ 8 weeks in patients with lower-risk myelodysplastic syndromes with ring sideroblasts.
- Researchers assessed patients’ baseline hemoglobin levels, serum ferritin levels, RBC transfusion burden, and erythroid response.
- The maximum dose of luspatercept (1.75 mg/kg) was received by most initial nonresponders who continued luspatercept therapy, and 16% of these patients achieved RBC-TI for ≥ 8 weeks during weeks 25-48.
- Luspatercept treatment reduces transfusion requirements and visits up to week 25, irrespective of baseline transfusion burden.
- Continuing luspatercept beyond week 25 may offer further clinical benefits to initial nonresponder
RBC-TI is a critical endpoint in treating lower-risk myelodysplastic syndromes. MEDALIST phase 3 trial showed that luspatercept could achieve RBC-TI of ≥ 8 weeks in more patients than placebo within 24 weeks. A post hoc analysis evaluated RBC transfusion units and visits based on baseline transfusion burden and clinical benefits of luspatercept treatment RBC-TI ≥ 8 weeks by week 25 for initial nonresponders who continued treatment up to 144 weeks. The study investigated baseline hemoglobin levels, serum ferritin levels, RBC transfusion burden, and erythroid response. The results showed that luspatercept-treated patients had fewer RBC transfusion units and visits than the placebo group up to week 25, regardless of their initial transfusion burden.
Luspatercept treatment continued for up to 144 weeks, especially in patients with low baseline transfusion burden. Among the initial nonresponders at week 25 who continued treatment, 81% received the maximum dose of luspatercept, and 16% achieved RBC-TI for ≥ 8 weeks during weeks 25-48. Furthermore, 44% had lower serum ferritin levels, 10% had an erythroid response, and 26% had a lower RBC transfusion burden. Their hemoglobin levels rose from baseline by an average of 1.3 g/dL.
The study showed that luspatercept treatment could lead to fewer transfusion units and visits in lower-risk MDS patients with ring sideroblasts, irrespective of baseline transfusion burden, up to week 25. Continuing luspatercept therapy beyond week 25 may provide additional clinical benefits for initial nonresponders, including increased RBC-TI duration, reduced RBC transfusion burden, improved erythroid response, reduced serum ferritin levels, and increased hemoglobin levels. These results have potential implications for clinical practice and highlight the importance of considering luspatercept as a treatment option for lower-risk MDS patients with ring sideroblasts.
Source: https://pubmed.ncbi.nlm.nih.gov/36635381/
Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT02631070/
Germing U, Fenaux P, Platzbecker U, Buckstein R, Santini V, Díez-Campelo M, Yucel A, Tang D, Fabre S, Zhang G, Zoffoli R, Ha X, Miteva D, Hughes C, Komrokji RS, Zeidan AM, Garcia-Manero G. Improved benefit of continuing luspatercept therapy: sub-analysis of patients with lower-risk MDS in the MEDALIST study. Ann Hematol. 2023 Feb;102(2):311-321. doi: 10.1007/s00277-022-05071-8. Epub 2023 Jan 13. PMID: 36635381; PMCID: PMC9889415.
