Multicenter phase 3 trial of carfilzomib-lenalidomide-dexamethasone versus lenalidomide maintenance after aHSCT for multiple myeloma

Lenalidomide maintenance has long been a preferred treatment after autologous HSCT in patients with multiple myeloma (MM). The phase 3 ATLAS trial, at 12 centers in the USA and Poland, evaluated maintenance with carfilzomib-lenalidomide-dexamethasone for these patients. The trial enrolled 180 adult patients with newly diagnosed MM with at least stable disease after autologous HSCT and an ECOG performance status of 0 or 1. Patients were randomized 1:1 to carfilzomib-lenalidomide-dexamethasone (n=92) or lenalidomide alone (n=88). Patients in the combination group with standard cytogenetic risk were switched to lenalidomide maintenance after cycle 8 if no measurable residual disease was detected after cycle 6. The primary endpoint was progression-free survival (PFS). At a median follow-up of 69 months (IQR 57-77), 4-year PFS rate was 67.5% with the combination versus 38.0% with lenalidomide (p<0.0001; median PFS 72.8 months versus 37.3 months; HR 0.46; p=0.0002). Serious adverse events occurred in 30% of the patients in the combination group and 23% of the patients in the lenalidomide group. Two deaths in each of both groups were considered possibly related to treatment. The authors conclude that these results support strategies for maintenance therapy intensification in this setting.