Final Sintra-Rev Results Favor Lenalidomide in Non-Transfusion-Dependent, Low-Risk MDS

Final results from the multicenter, phase III Sintra-Rev trial presented at the 2022 American Society of Hematology (ASH) Annual Meeting and Exposition confirmed the benefit of low-dose lenalidomide in anemic, non-transfusion-dependent (TD) low-risk myelodysplastic syndromes (MDS) patients with deletion 5q (del5q).

A multinational team led by presenter Félix López Cadenas, MD, of Hospital Clínico Universitario de Salamanca in Salamanca, Spain, found that lenalidomide prolonged the time to transfusion dependence, improved hemoglobin levels, and induced good-quality clonal responses. It also has a manageable safety profile and doesn’t result in increased progression rate or clonal evolution, according to the authors.

Sintra-Rev, the first randomized trial to assess the role of lenalidomide in non-TD anemia in del5q MDS, utilized a double-blind design to randomize patients to receive placebo or lenalidomide 5 mg. Participants received two years of treatment and an additional two years of follow-up. The study included 61 patients, of whom 54 were evaluable for the analysis.

The researchers had previously reported interim results at the 2020 ASH Annual Meeting, which showed early treatment with lenalidomide prolonged transfusion-free survival and that lenalidomide-treated patients had a 72% erythroid response rate and a 80% cytogenetic response rate.

The final results for Sintra-Rev were similar to the interim findings.

The difference in time to TD was statistically significant (P=.021), as were differences in cytogenetic response and hematologic improvement (both P<.001). Among treatment responders, the median hemoglobin improvement was 2.7 g/dL. See TABLE 1 for more outcomes.

Acute myeloid leukemia evolution and median overall survival were similar for both sets of patients. There were also no differences in clonal evolution.

Notably, next-generation sequencing analysis during follow-up showed that the mean number of mutations per patient were reduced at week 12 in those receiving lenalidomide, declining from 1.21 prior to treatment to 0.84 afterward. There were no differences in the placebo group.

In terms of safety, 58 patients had at least one adverse event in the trial, but there were no significant differences in frequency of events between the two study arms.

Reference

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. Abstract #460. Presented at the 64th American Society of Hematology Annual Meeting, December 10-13, 2022; New Orleans, Louisiana.