DP023 | LUSPATERCEPT FOR THE TREATMENT OF TRANSFUSION-DEPENDENT ANEMIA IN PATIENTS WITH MYELODYSPLASTIC NEOPLASMS WITH DEL5Q, REFRACTORY/RESISTANT/INTOLERANT TO PRIOR TREATMENTS (QOL-ONE PHOENIX)

Background: Myelodysplastic neoplasms (MDS) with deletion 5q (del5q) are characterized by red blood cell transfusion dependence (RBC-TD and about one third of patients are refractory/resistant/ineligible to lenalidomide. Luspatercept is approved for lower risk MDS requiring transfusions. We present interim results of a multicenter single arm trial to evaluate the efficacy of luspatercept in adult patients with RBC-TD MDS with del5q refractory/resistant/intolerant to prior treatments. Methods: The primary endpoint is transfusion independence (TI) for 8 consecutive weeks within the first 24 weeks. Secondary endpoints include safety, tolerability, and changes in quality of life (QoL) using QOL-E and HM-PRO measures. Patients received luspatercept at a starting dose of 1.0 mg/kg every 3 weeks for up to 2 years, with dose titrations up to a maximum of 1.75 mg/kg or reduced, as appropriate. Non-responders at 24 weeks and those losing response interrupt treatment and continue a follow-up. Results: 22 patients (16 females) of median age 76 years (range 40-94) have been enrolled. Median baseline hemoglobin (Hb) is 8.7 (6.4–9.7) g/dL with median RBC transfusion requirement of 4 (2-14) units in the preceding 8 weeks. Ten cases had a high transfusion burden (HTB). At interim, 13 cases have reached 24 weeks in the trial: 6 patients (46%) reached RBC-TI with concurrent increase in Hb>10 g/dL (table) and another HTB case achieved a >50% reduction in RBC units. Five patients continue on therapy, while 1 responsive patient received a stem cell transplantation. Changes in QOL-E fatigue (r2=0.607; p=0.036) and HM-PRO Part-A scores (r2=-0.644; p=0.024) correlated with improvements in Hb. Responders showed a clinically meaningful improvement in QOL-E physical functioning in 5 cases, as well as in other domains. One responder experienced an unrelated grade 3 paresthesia, 1 non-responder evolved to acute leukemia, and two deaths occurred due to pneumonia (one during response). Conclusion: This interim analysis shows that luspatercept is effective in a substantial proportion of cases, with concurrent improvements in Hb levels, while maintaining a favorable safety profile. Additionally, a notable improvement in QoL, particularly in physical functioning, is reported. Longer follow-up is required to confirm the durability of these benefits.