Luspatercept in Clinical Practice: Real-World Dose Escalation and Outcomes Among Patients With Lower-Risk MDS Receiving Luspatercept in Clinical Practice

Luspatercept has been approved for the treatment of anemia in patients with lower-risk myelodysplastic syndromes (MDS), with or without prior use of erythropoiesis-stimulating agents, who may require regular red blood cell (RBC) transfusions. The recommended starting dose of luspatercept is 1 mg/kg once every 3 weeks, with the possibility of dose escalation to 1.33 and 1.75 mg/kg for transfusion-dependent (TD) patients who remain so after ≥2 consecutive doses (6 weeks).

Nevertheless, the literature has not adequately characterized the real-world dose adjustment and subsequent clinical outcomes. This research aimed to assess the clinical advantages of adjusting the dosage of luspatercept for patients with lower-risk MDS in the United States who began treatment with luspatercept in various lines of therapy.

This research utilized electronic medical records from the Integra PrecisionQ deidentified database containing more than 3 million community-based oncology patient records. Patients aged ≥18 years, diagnosed with lower-risk MDS (Revised International Prognostic Scoring System [IPSS-R] score of very low, low, or intermediate risk) between January 1, 2016, and June 30, 2022, who received luspatercept, underwent a first luspatercept dose escalation up to 1.33 mg/kg (not the maximum approved dose), continued treatment for at least 8 weeks at the same escalated dose.

Patients were categorized as non-TD (NTD)/transfusion independent (TI) if they received no RBC units and TD if they received ≥1 RBC units. Key clinical outcomes post luspatercept dose escalation included TI rates for ≥8 weeks in patients who were TD before dose escalation and changes in hemoglobin (Hb) levels in patients who were NTD before dose escalation.

Of the 350 patients who received luspatercept, 94% had complete information about their dosage, and 72% experienced a first dose escalation. Among those with a dose escalation, 54% continued with the same escalated dose for ≥8 weeks and were included in this study. The average age of the patients was 74.0 years.

The study included primarily men (55%), and 94% were treated in community practices. Among the patients, 45% had MDS with ring sideroblasts, and 99% had very low/low IPSS-R scores at the time of diagnosis. Luspatercept was the first line of treatment for 6% of patients, 71% for the second line, and 23% for the third line. A total of 66 patients were TD, and 61 were NTD before the dose escalation.

Among the 61 patients who were NTD before the first dose escalation, Hb levels generally increased after the first dose escalation. Out of the 11 NTD patients who became TD after the dose escalation, all had received luspatercept as their second (n=8) or third (n=3) line of treatment. Most (70%) of the patients who were NTD before the dose escalation had their first dose escalation occurring ≥3 to 6 weeks (23%), ≥6 to 9 weeks (18%), or ≥21 weeks (30%) after the initiation of luspatercept.

Proper dose escalation of luspatercept in clinical settings could lead to achieving transfusion independence in patients with lower-risk MDS who are TD. For patients who are not TD, increasing the dose of luspatercept may aid in sustaining NTD and promoting higher Hb levels.

Source: Patel K, Chatterjee D, Hughes C, et al. Real-world dose escalation and outcomes among patients with lower-risk myelodysplastic syndromes receiving luspatercept in clinical practice. Madrid, Spain, & online: presented at EHA2024 Hybrid Congress; abstract P768.