Photo courtesy of Celgene
WASHINGTON, DC—Results of a phase 3 trial support the use of lenalidomide in patients with lower-risk myelodysplastic syndromes (MDS) without 5q deletion who are unresponsive or refractory to erythropoiesis-stimulating agents (ESAs), according to researchers.
About 27% of patients who received lenalidomide achieved transfusion independence for 8 weeks or more, and about 18% were transfusion-independent for 24 weeks or more.
Valeria Santini, MD, of AOU Careggi in Florence, Italy, and her colleagues presented these results at the 13th International Symposium on Myelodysplastic Syndromes (abstract 115). The trial, MDS-005, was supported by Celgene Corporation, the company developing lenalidomide.
The trial was a comparison of lenalidomide and placebo in 239 patients with non-del-5q MDS who had failed treatment with ESAs. The patients were transfusion-dependent and had low- or intermediate-1-risk disease according to the International Prognostic Scoring System.
Patients were randomized 2:1 to receive oral lenalidomide at 10 mg once daily on days 1 to 28 of 28-day cycles (5 mg for patients with creatinine clearance 40 to 60 mL/min) or placebo.
Significantly more patients in the lenalidomide arm than in the placebo arm achieved transfusion independence for 8 weeks or more—26.9% vs 2.5% (P<0.001).
Likewise, significantly more patients in the lenalidomide arm than in the placebo arm achieved transfusion independence for 24 weeks or more—17.5% vs 0% (P<0.001).
Ninety percent of the lenalidomide-treated patients who achieved transfusion independence for 8 weeks or more responded within 4 cycles of treatment. The median duration of response was 32.9 weeks.
The median follow-up was 1.6 years (range, 0-3.6) in the lenalidomide arm and 1.3 years (range, 0-4.0) in the placebo arm. Within these time periods, patients in the placebo arm were more likely than those who received lenalidomide to progress to acute myeloid leukemia (AML) or to develop second primary malignancies (SPMs).
The AML incidence rate per 100 person-years was 1.91 in the lenalidomide arm and 2.46 in the placebo arm. And the SPM incidence rate per 100 person-years was 2.19 in the lenalidomide arm and 2.27 in the placebo arm.
As expected, treatment-emergent adverse events (AEs) were more common in the lenalidomide arm than in the placebo arm. AEs included neutropenia (64.4% vs 12.7%), thrombocytopenia (39.4% vs 7.6%), diarrhea (42.5% vs 22.8%), constipation (22.5% vs 12.7%), infections (51.9% vs 43%), hemorrhage (20.6% vs 10.1%), hepatic disorders (14.4% vs 5.1%), cardiac arrhythmia (11.3% vs 8.9%), and cutaneous reactions (10% vs 1.3%).
Grade 3-4 AEs in the lenalidomide arm included neutropenia (61.9%), thrombocytopenia (35.6%), infections (14.4%), hepatic disorders (5%), diarrhea (2.5%), hemorrhage (1.9%), deep vein thrombosis (1.9%), cardiac arrhythmia (1.3%), and cutaneous reactions (1.3%).
Based on the results of this trial, Celgene plans to submit a regulatory filing with the US Food and Drug Administration in the second half of 2015. Lenalidomide is not approved in the US to treat patients with non-del-5q MDS.
