In a phase III U.S. Intergroup trial reported in the Journal of Clinical Oncology, Alan F. List, MD, and colleagues found that treatment with lenalidomide plus epoetin alfa increased the rate of major erythroid response vs lenalidomide alone in patients with lower-risk, non-del(5q) myelodysplastic syndromes (MDS) who were also anemic.

As stated by the investigators, “Impaired response to erythropoietin underlies ineffective erythropoiesis and anemia in MDS. We investigated whether treatment with lenalidomide, which augments erythropoietin receptor signaling in vitro, can restore and improve hemoglobin response to epoetin alfa…in [this setting].”

Alan F. List, MD

Study Details

In the trial, 195 patients with MDS who had anemia refractory to or had low probability of benefit from recombinant erythropoietin treatment were randomly assigned between January 2009 and May 2016 to receive lenalidomide plus epoetin alfa (n = 99) or lenalidomide alone (n = 96). Overall, 157 patients (81%) were assigned to receive lenalidomide at 10 mg once daily (n = 81 in combination group and n = 76 in lenalidomide group), with 38 receiving lenalidomide at 5 mg once daily. The primary endpoint was major erythroid response at week 16.

Major Erythroid Response

In intent-to-treat analysis, major erythroid response was achieved by 28 patients in the combination group and 11 in the lenalidomide group (28.3% vs 11.5%, P = .004). Among 136 patients who completed 16 weeks of study treatment, major erythroid response was achieved in 28 (38.9%) of 72 patients in the combination group vs 10 (15.6%) of 64 in the lenalidomide group (P = .004). In the total population, minor erythroid response was achieved in an additional 18.2% vs 20.8% of patients, for an overall erythroid response rate of 46.5% vs 32.3% (P = .057).

Among patients who did not respond to lenalidomide alone, 10 (26.3%) of 38 who crossed over to receive the addition of epoetin alfa achieved major erythroid response. Median duration of major erythroid response was 23.8 months among the 39 patients (including 10 crossover patients) with response to the combination vs 13 months among patients with response to lenalidomide alone (P = .24).

Adverse Events

Grade ≥ 3 hematologic adverse events were consistent with those in previously reported trials of patients with non-del(5q) MDS. There was no significant difference between groups in frequency of grade ≥ 3 nonhematologic adverse events. The most commonly reported adverse events among all patients were fatigue (8% vs 3%), maculopapular rash (3% vs 4%), febrile neutropenia (4% vs 2%), and diarrhea (3% vs 2%). Treatment was discontinued due to adverse events in 20% vs 17% of patients. Treatment-related death occurred in two patients in each group.

The investigators concluded: “Lenalidomide restores sensitivity to recombinant erythropoietin in growth factor–insensitive, lower-risk, non-del(5q) MDS, to yield a significantly higher rate and duration of major erythroid response compared with lenalidomide alone.”

Amit Verma, MD, of Albert Einstein College of Medicine, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was funded by the National Cancer Institute. For full disclosures of the study authors, visit ascopubs.org.