ORLANDO—In newly diagnosed multiple myeloma, the greatest benefits of continuous lenalidomide maintenance after melphalan, prednisone, and lenalidomide induction (MPR-R) are conferred to patients aged between 65 and 75 years. The finding emerged from results of the MM-015 study presented by Antonio Palumbo, MD, University of Torino, Italy. Palumbo’s analysis of the phase 3 study also showed continuous lenalidomide therapy to be superior to regimens of limited duration.
The MM-015 study evaluated the efficacy and safety of continuous lenalidomide maintenance after MPR-R induction versus fixed-duration regimens of melphalan and prednisone (MP) or melphalan, prednisone, and lenalidomide (MPR) in 459 transplant-ineligible patients aged ≥65 years.
Patients were randomized to MPRR, MPR, or MP, receiving melphalan 0.18 mg/kg (days 1-4) and prednisone 2 mg/kg (days 1-4), with or without lenalidomide 10 mg/day (days 1-21) for nine 28-day cycles. Following nine cycles of MPR, patients received maintenance lenalidomide 10 mg/day (days 1-21) or placebo until progression; MP patients received placebo until progression.
Nearly 50% of patients were high risk (International Staging System [ISS] stage III). Typical multiple myeloma trials, Palumbo commented, include 25% to 30% high-risk patients. Median patient age was 71 years.
Response improved over time, such that the rates of more than a very good partial response continued to increase through nine treatment cycles, reaching nearly 30% compared with about 10% for MP. Time to response, Palumbo noted, was much shorter for the three-drug combination.
Risk of progression was reduced 60% for MPR-R at a median follow-up of 25 months. Median progression-free survival (PFS) was 31 months for MPR-R, 14 months for MPR, and 13 months for MP (P <.0000001 for MPR-R vs MP; hazard ratio, 0.398). “This is a PFS you might see in many studies with autologous transplant,” Palumbo commented.
Although median PFS among patients aged 65 to 75 years was not yet reached (risk reduced by 69%), median PFS among patients aged >75 years was not reduced.
Adverse events led to discontinuations in 19% of patients in the older group, despite a lower dose intensity of approximately 50%. “This tells us that it is very important in the future to define a schema for patients older than 75, because in frail patients we are ending up with too high a discontinuation rate.”
Neutropenia and thrombocytopenia were higher in the lenalidomide-containing regimens. Among patients receiving lenalidomide-containing regimens, solid tumors were reported in <4%, acute myelogenous leukemia (AML) in 3%, and myelodysplastic syndrome in <3%. Palumbo noted that risk of secondary tumors and AML in patients receiving autologous transplants or alkylating agents in previous reports among larger sequences of patients has been as high as 8%.
Overall survival was similar between groups (1 year, 92%-93%; 2 years 75%- 82%). Overall survival hazard ratios favored MPR-R over MP in all subgroups (aged ≤75 years, lower ISS stage, good renal function, low beta-2 microglobulin ≤5.5 mg/L) except for patients aged >75 years.
“MPR-R is highly active, with the greatest benefit in patients [aged] 65 to 75 years,” Palumbo concluded at his presentation. He added, “Continuous lenalidomide therapy achieved an unprecedented median PFS of 31 months.”