Initial Safety Findings Reported on Luspatercept Plus Lenalidomide for Non-Del(5q) MDS

A multicenter, phase Ib/II trial is underway to investigate the combination of luspatercept and lenalidomide for anemia in patients with very low to intermediate risk myelodysplastic syndromes (MDS) without chromosome 5q deletion. Results from the trial’s phase Ib component were presented at the 66^th American Society of Hematology Annual Meeting & Exposition in San Diego, California.

Lead author for the study Mikkael Sekeres, MD, from the Sylvester Cancer Center at the University of Miami, Florida, reported that the combination “was well-tolerated, and a recommended phase II dose was established, with that trial ongoing. The preliminary response rate appeared at least similar to either monotherapy.”

The phase Ib cohort involved 12 patients with a median age of 69 years who were 20% female, and at baseline had a median transfusion need of four packed red blood cells every 16 weeks. 50% of the cohort had received a prior erythropoiesis stimulating agent, 33% a prior hypomethylating agent, and 33% were treatment-naive.

In a 21-day cycle, the patients received subcutaneous luspatercept with standard dose titration for insufficient response and oral lenalidomide which was escalated to ascertain a maximum tolerated dose (MTD).

During the dose-limiting toxicity (DLT) evaluation period, the cohort experienced no DLTs but had 49 occurrences of grade 1 and 30 of grade 2 adverse events (AEs). Decreased neutrophil counts were the most common hematologic AE at 16 instances, followed by nine instances of decreased platelet count, and six of anemia. Regarding non-hematologic AEs, there were five instances of diarrhea, four of muscle cramps, three of fatigue, and three of lung infection.

The cohort had a median follow-up of 22.5 weeks. During follow-up, it experienced 62 instances of non-hematologic AEs, 39 of which were grade 1, 19 grade 2, and four were grade 3 or worse severity. The most common AEs were infections gastrointestinal in nature.

Luspatercept was escalated in eight patients and reduced after cycle 1 in four patients. Ten patients of the cohort were evaluable for hematologic improvement response, which was achieved by five. Four of them had erythroid hematologic improvement, three of whom attained transfusion independence.

The MTD for lenalidomide was not reached in this phase I component of the trial. However, the investigators were able to determine for the study doublet a recommended phase II dose of lenalidomide 10 mg daily and luspatercept 1.0 mg/kg on the first day of a 21-day cycle.

Reference

Sekeres MA, Carraway HE, Stone RM, et al. A multicenter, phase Ib/II study that combines luspatercept and lenalidomide (L2) in lower-risk, non-del(5q) patients with myelodysplastic syndromes: Phase Ib results. Abstract #1821. Presented at the 66th American Society of Hematology Annual Meeting and Exposition; December 7-10, 2024; San Diego, California.