The use of lenalidomide (LEN) plus epoetin (EPO) alfa vs LEN alone appeared to improve the rate of major erythroid response in patients with nondel(5q), lower-risk myelodysplastic syndromes (MDS) who were refractory to erythropoietin, according to the results of a phase 3 clinical trial published in the Journal of Clinical Oncology.
This trial (ClinicalTrials.gov Identifier: NCT00843882) included patients with low- to intermediate-risk MDS with anemia. Patients who were unresponsive or lost response to recombinant erythropoietin treatment, or were otherwise considered to have a low probability of response to erythropoietin, were eligible for participation. Patients were randomly assigned to treatment with either LEN-EPO alfa or LEN alone. Only patients with nondel(5q) status were evaluated in this study. The primary study endpoint was major erythroid response.
The LEN-EPO alfa cohort consisted of 99 patients, and the LEN-only cohort had 96 patients. Following 4 cycles of treatment, major erythroid response was reported among 28.3% for patients receiving the combination, and 11.5% among patients receiving LEN alone (P =.004).
Median duration of major erythroid response was 23.8 months with the combination treatment and 13 months with LEN monotherapy (log-rank P =.24). The overall erythroid response rates were 46.5% for the combination cohort and 32.3% for the LEN-only cohort (P =.057). Improvements in hemoglobin levels were similar between arms (P =.79). Of the 65 patients who did not response to LEN monotherapy, 38 patients crossed over to the combination treatment group, 10 of whom major erythroid response following crossover (26.3%).
A univariate analysis of patient DNA samples suggested that patients who did not respond more often lacked mutations compared with patients who achieved major erythroid response (21.1% vs 3.7%; P =.031), but this pattern was not demonstrated in a multivariate analysis. Duration of major erythroid response did not appear to differ based on numbers or types of mutations. However, among patients with DNA repair-related mutations, median duration of major erythroid response showed a nonsignificant trend of being shorter, at 4.1 months vs 8.5 months without such mutations (log-rank P =.054).
The most common grade 3 or greater adverse events were anemia, neutropenia, and thrombocytopenia in both treatment groups. Treatment discontinuations related to adverse events were reported in 20.2% of patients on the combination therapy and in 16.7% of patients receiving LEN only. Each study arm reported 2 fatalities.
The study investigators indicated that LEN may enable restored sensitivity to recombinant erythropoietin in patients with lower-risk, nondel(5q) MDS. They concluded in this study that the combination therapy provided both a higher rate and longer duration of major erythroid response than seen with LEN monotherapy in this patient population.
Disclosure: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.
List AF, Sun Z, Verma A, et al. Lenalidomide-epoetin alfa versus lenalidomide monotherapy in myelodysplastic syndromes refractory to recombinant erythropoietin. J Clin Oncol. Published online January 13, 2021. doi:10.1200/JCO.20.01691