In a final analysis, low-dose lenalidomide prolonged time to transfusion dependence among patients with low-risk myelodysplastic syndrome (MDS) with a 5q deletion (del[5q]) and anemia, according to the results of the SINTRA-REV phase 3 trial presented at the 2022 ASH Annual Meeting.
Among patient with transfusion dependency, 10 mg of lenalidomide is effective in leading to transfusion independence and CyR. Given that 68% of patients with low-risk MDS present with anemia without transfusion dependency, the investigators asked if low-dose lenalidomide could prolong time to dependency and improve outcomes, Maria Diez-Campelo, MD, of the Hospital Universitario de Salamanca-IBSAL in Spain, said when presenting the study.
The multicenter, double-blind, phase 3 SINTRA-REV trial randomly assigned 61 patients with low-risk MDS with del(5q) 2:1 to receive 5 mg of lenalidomide or placebo for 2 years, and all patients were followed for an additional 2 years. All patients had anemia but were not transfusion dependent at enrollment. The primary endpoint was time to transfusion dependence and secondary endpoints included cytogenetic response (CyR), overall survival (OS), and time to developing acute myeloid leukemia (AML). The median follow-up was 60.6 months in this final analysis.
The median age at baseline was 72 and 83% of patients were female. The median hemoglobin level was 9.8 g/dL. The median time on lenalidomide treatment was 95.9 weeks and 42.7 weeks with placebo. There were 47.1% and 83.3% of patients in the lenalidomide and placebo arms, respectively, who discontinued treatment due to progressive disease and transfusion requirement.
Time to transfusion dependence was significantly longer with lenalidomide, at a median that was not reached compared with 11.6 months with placebo (hazard ratio [HR], 0.302; 95% CI, 0.132-0.692; P =.005).
The rate of erythroid response was 77.8% in the lenalidomide arm and 0% in the placebo arm (P <.01). CyR was achieved by 94% of patients in the lenalidomide arm compared with 0 in the placebo arm (P <.001).
The rate of AML evolution was 15% with lenalidomide compared with 23.8% with placebo (P =.488). However, next-generation sequencing analysis demonstrated a reduction in the mean number of mutations for each patient compared with no changes in the placebo arm.
The most common adverse events (AEs) in the lenalidomide group were gastrointestinal, rash, and asthenia, the majority of which were grade 1-2 in severity. The most common hematologic grade 3-4 AEs were neutropenia.
OS was similar between the treatment groups. AML developed in 6 patients in the lenalidomide arm and 5 patients in the placebo group.
Dr Diez-Campelo concluded that “finally, with all the data, we can confirm that early treatment with lenalidomide with low doses during 2 years prolongs the time and decreases the risk of transfusion dependency with a promising response and acceptable safety profile.”
Disclosures: Some of the study authors declared affiliations with biotech, pharmaceutical, or device companies. Please see the original reference for a full list of disclosures.
Cadenas FL, Lumbreras E, González T, et al. Evaluation of lenalidomide (LEN) vs placebo in non-transfusion dependent low risk del(5q) MDS patients. Final results of Sintra-REV phase III international multicenter clinical trial. Presented at ASH 2022. December 10-13, 2022. Abstract 460.