Lenalidomide is currently licensed only for previously treated multiple myeloma (MM) patients in Europe. A phase III trial, comprising 459 patients, evaluated lenalidomide as first-line therapy for transplant-ineligible patients. Within this three-armed trial, lenalidomide induction therapy with melphalan and prednisone followed either by lendalidomide maintenance therapy (MPR-R arm) or by placebo maintenance (MPR) and placebo with melphalan and prednisone followed by placebo maintenance therapy (MP arm) were compared.

The primary outcome was progression-free survival (PFS) in the MPR-R group compared to the MP group. Overall, median PFS was 31 months in the MPR-R group, 14 months in the MPR and 13 months in the MP group, yielding a gain of 17 months for the MPR-R group in comparison to the MPR group and of 18 months in comparison to the MP group. Furthermore, complete or partial responses, were superior for the two groups which had received lenalidomide and duration of response was significantly longer for the maintenance lenalidomide group (MPR-R) than for those with placebo maintenance. Higher grade haematologic AEs during induction therapy occurred more often
in the lenalidomide groups than in the placebo group; 2% of deaths in the MPR-R group and 1% in the MPR group respectively, were considered as treatment-related but no results were provided for the MP group. Second primary tumours developed in 7% of patients in the two lenalidomide groups in contrast to 3% in the MP group.

The increase in PFS was mainly attributable to lenalidomide maintenance therapy, but only about 60% of patients entered this phase. Furthermore, subjects receiving maintenance therapy showed better baseline characteristics than the overall study population. Also, since no commonly accepted criteria for determination of transplant eligibility -besides age- exist (co-morbidities and the biological age are being considered), it remains questionable if the primary inclusion criteria (i.e. ≥65 years, Karnofsky performance score ≥60%, no serious medical condition) actually led to the enrolment of patients who would be deemed transplant-ineligible in clinical practice. In addition, data on both, adverse events -specifically for elderly patients- and quality of life are missing.