New Analysis From COMMANDS Trial Reveals More Luspatercept Benefits

Luspatercept can do more than just yield red blood cell (RBC) transfusion independence in erythropoiesis-stimulating agent (ESA)-naive patients with transfusion-dependent (TD) lower-risk myelodysplastic syndromes (MDS), according to research presented at the Eleventh Society of Hematologic Oncology Annual Meeting in Houston.

In an analysis of 301 patients from the COMMANDS trial, a multinational team led by presenter Rami Komrokji, MD, of Moffitt Cancer Center, Tampa in Florida, and colleagues found that luspatercept also led to durable increases in hemoglobin and lower transfusion burden.

“Luspatercept may represent a new standard of treatment for ESA-naive patients with [transfusion dependent] [lower-risk] MDS,” the researchers concluded.

The COMMANDS trial showed that luspatercept delivered durable RBC transfusion independence compared with epoetin alfa in ESA-naive patients with lower-risk MDS. In this study, the researchers sought to report additional benefits of luspatercept from the trial.

Of the 301 patients in the planned interim analysis of 301 patients, 86 (58.5%) of the 147 patients who received luspatercept and 48 (31.2%) of the 154 patients who were given epoetin alfa achieved the study’s primary endpoint: RBC transfusion independence of at least 12 weeks with a concurrent mean hemoglobin increase for at least 12 weeks with concurrent mean hemoglobin increase of at least 1.5 g/dL (weeks 1–24). That difference was statistically significant (P<.0001). See TABLE 1.

TABLE 1. Benefits of Luspatercept versus Epoetin Alfa Group

Patient outcomes	Epoetin alfa group (%)	Luspatercept group (%)	P value
Mean hemoglobin increase ≥ 1.5 g/dL (weeks 1-24)	48.7	72.1	< .0001
RBC transfusion independence ≥ 12 weeks (week 1 to end of trial)	46.1	66.7	= .0002
Patients achieving ≥ 50% reduction in pRBC units ≥ 12 weeks	65.6	81.6	= .0016
Median duration of transfusion burden reduction	86.9 weeks	130 weeks	N/A

 

The median duration of longest hemoglobin increase of at least 1.5 g/dl and median duration of RBC transfusion independence was also higher among the luspatercept group. In other findings, the researchers found that 125 (70.2%) of patients in the luspatercept group had an escalated dose, a comparable proportion to the 131 (74.4%) of 176 patients in the epoetin alfa group.

Delving further into those results, they found that 122 (68.5%) of luspatercept patients escalated from 1.0 to 1.33 mg/kg and 88 (49.4%) had an escalated dose from 1.33 to 1.75 mg/kg. In the epoetin alfa group, 129 (73.3%) escalated from 450 to 787.5 IU/kg and 102 (58%) had an escalated dose from 787.5 to 1050 IU/kg, according to the researchers.

“Luspatercept demonstrated clinical benefit beyond RBC-[transfusion independence], including durable hemoglobin increases and [transfusion burden] decreases, with dose increases consistent with previous studies, shown for the first time in an ESA-naive patient population,” the authors wrote.

The study was funded by Bristol Myers Squibb.

Reference

Komrokji R, Platzbecker U, Della Porta M, et al. Reduction of transfusion burden (TB), hemoglobin increase, and dose titration in the COMMANDS study of luspatercept versus epoetin alfa (EA) in erythropoietin-stimulating agent (ESA)-naive patients with transfusion-dependent (TD) lower-risk myelodysplastic syndromes (LR-MDS). Abstract MDS 234. Presented at the Eleventh Annual Meeting of the Society of Hematologic Oncology; September 6-9, 2023; Houston, Texas.