Randomized Phase III Study of Lenalidomide Versus Placebo in RBC Transfusion-Dependent Patients With Lower-Risk Non-del(5q) Myelodysplastic Syndromes and Ineligible for or Refractory to Erythropoiesis-Stimulating Agents | Aplastic Anemia and MDS International Foundation

Randomized Phase III Study of Lenalidomide Versus Placebo in RBC Transfusion-Dependent Patients With Lower-Risk Non-del(5q) Myelodysplastic Syndromes and Ineligible for or Refractory to Erythropoiesis-Stimulating Agents

Journal Title: 
J Clin Oncol
Primary Author: 
Santini V
Author(s): 
Santini V, Almeida A, Giagounidis A, Gröpper S, Jonasova A, Vey N, Mufti GJ, Buckstein R, Mittelman M, Platzbecker U, Shpilberg O, Ram R, Del Cañizo C, Gattermann N, Ozawa K, Risueño A, MacBeth KJ, Zhong J, Séguy F, Hoenekopp A, Beach CL, Fenaux P
Original Publication Date: 
Monday, June 27, 2016

PURPOSE:

This international phase III, randomized, placebo-controlled, double-blind study assessed the efficacy and safety of lenalidomide in RBC transfusion-dependent patients with International Prognostic Scoring System lower-risk non-del(5q) myelodysplastic syndromes ineligible for or refractory to erythropoiesis-stimulating agents.

PATIENTS AND METHODS:

In total, 239 patients were randomly assigned (2:1) to treatment with lenalidomide (n = 160) or placebo (n = 79) once per day (on 28-day cycles). The primary end point was the rate of RBC transfusion independence (TI) ≥ 8 weeks. Secondary end points were RBC-TI ≥ 24 weeks, duration of RBC-TI, erythroid response, health-related quality of life (HRQoL), and safety.

RESULTS:

RBC-TI ≥ 8 weeks was achieved in 26.9% and 2.5% of patients in the lenalidomide and placebo groups, respectively (P < .001). Ninety percent of patients achieving RBC-TI responded within 16 weeks of treatment. Median duration of RBC-TI with lenalidomide was 30.9 weeks (95% CI, 20.7 to 59.1). Transfusion reduction of ≥ 4 units packed RBCs, on the basis of a 112-day assessment, was 21.8% in the lenalidomide group and 0% in the placebo group. Higher response rates were observed in patients with lower baseline endogenous erythropoietin ≤ 500 mU/mL (34.0% v 15.5% for > 500 mU/mL). At week 12, mean changes in HRQoL scores from baseline did not differ significantly between treatment groups, which suggests that lenalidomide did not adversely affect HRQoL. Achievement of RBC-TI ≥ 8 weeks was associated with significant improvements in HRQoL (P < .01). The most common treatment-emergent adverse events were neutropenia and thrombocytopenia.

CONCLUSION:

Lenalidomide yields sustained RBC-TI in 26.9% of RBC transfusion-dependent patients with lower-risk non-del(5q) myelodysplastic syndromes ineligible for or refractory to erythropoiesis-stimulating agents. Response to lenalidomide was associated with improved HRQoL. Treatment-emergent adverse event data were consistent with the known safety profile of lenalidomide.

Bone Marrow Diseases: