In a long-term follow-up of the German phase II PACE-MDS trial reported in the Journal of Clinical Oncology, Uwe Platzbecker, MD, and colleagues described erythroid, neutrophil, and platelet hematologic improvement rates with luspatercept treatment for anemia in patients with lower-risk myelodysplastic syndromes (MDS), including among MDS subtypes.
Study Details
In the multicenter study, 108 patients received luspatercept for up to 5 years. Among the 108 patients, 62 did and 44 did not have ring sideroblasts; 34 were non–transfusion dependent; and 29 and 45 had low and high transfusion burdens, respectively.
Uwe Platzbecker, MD
Key Findings
Overall, hematologic improvement–erythroid occurred in 58 (53.7%) of 108 patients including: 42 (67.7%) of 62 patients with ring sideroblasts vs 16 (36.4%) of 44 with non–ring sideroblasts (P = .002), 24 (70.6%) of 34 non–transfusion dependent patients, 17 (89.5%) of 19 non–transfusion dependent patients with ring sideroblasts, 10 (34.5%) of 29 low–transfusion burden vs 24 (53.3%) of 45 high–transfusion burden patients (P = .115), and 7 (46.7%) of 15 non–transfusion dependent patients with non–ring sideroblasts, 3 (23.1%) of 13 low–transfusion burden patients with non–ring sideroblasts, and 6 (37.5%) 16 high–transfusion burden patients with non–ring sideroblasts. Hematologic improvement–erythroid was observed in 35 (74.5%) of 47 patients with SF3B1 mutations vs 19 (38.8%) of 49 with wild-type SF3B1 (P < .001), and 6 (33.3%) of 18 with non-SF3B1 splicing factor mutations vs 13 (41.9%) of 31 with no splicing factor mutations (P = .031).
Hematologic improvement–erythroid response was accompanied by a nearly threefold increase in bone marrow late to early progenitor cell ratio, irrespective of ring sideroblast status, and was associated with lower baseline erythropoietin levels in non–ring sideroblast patients (69.6 vs 623.3 IU/L, P = .008) and higher late to early erythroid progenitor cell ratio (10.44 vs 4.48, P = .011) in ring sideroblast patients.
Hematologic improvement–neutrophil was observed in 8 (33.3%) of 24 patients, including 4 (25.0%) of 16 non–ring sideroblast and 6 (46.2%) of 13 high–transfusion burden patients, 4 (80.0%) of 5 with SF3B1 mutations vs 6 (42.9%) of 14 with wild-type SF3B1 (P = .224), and 1 (33.3%) of 3 with non-SF3B1 splicing factor mutations vs 5 (45.5%) of 11 with no splicing factor mutations (P = .894).
Hematologic improvement–platelet was observed in 2 (9.5%) of 21 patients overall, including 1 (20.0%) of 5 with SF3B1 mutations vs 4 (33.3%) of 12 with wild-type SF3B1 (P = .509) and 2 (50.0%) of 4 with non-SF3B1 splicing factor mutations vs 2 (25.0%) of 8 with no splicing factor mutations (P = .418).
No new safety signals were identified.
The investigators concluded: “This study highlights luspatercept’s effects across lower-risk MDS subtypes… serving as a platform for future trials.”
Dr. Platzbecker, of Medical Clinic and Policlinic 1, Leipzig University Hospital, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Acceleron Pharma, Inc, in collaboration with Bristol Myers Squibb. For full disclosures of the study authors, visit ascopubs.org.
