LENALIDOMIDE AND DEXAMETHASONE WITH OR WITHOUT IXAZOMIB MAINTENANCE TAILORED BY RESIDUAL DISEASE STATUS IN MYELOMA.

From November 2014 to May 2017, 332 patients homogeneously treated with VRD induction, ASCT and VRD consolidation were randomized to receive maintenance therapy with RD (161 patients) vs IRD (171 patients). RD consisted of lenalidomide 15 mg/d from days 1-21 plus dexamethasone 20 mg/d on days 1-4 and 9-12 at 4-weeks intervals while in the IRD arm oral ixazomib at a dose of 4 mg on days 1,8, and 15 was added. MRD negative patients after 24 cycles were discontinued while those who were MRD positive remained on maintenance with RD for 36 more cycles. The MRD negativity from baseline increased from 50.9% to 71.8% with RD and from 59.6% to 72.4% with IRD at 2 years. After a median follow-up of 69 months from the initiation of maintenance, the PFS was similar in both arms, median not reached in either arm with a 6-years PFS rate of 61.3% and 55.6% for RD and IRD, respectively (HR 1.136 [95% CI 0.809 - 1.603]). No significant differences in PFS between RD and IRD were observed in any prognostic subgroup. After 2 years of maintenance, treatment was discontinued in 163 patients who were MRD negative while 63 MRD positive patients were continued on RD therapy. Maintenance discontinuation in MRD negative patients resulted in a low progression rate (17.2% at 4 years), even in patients with high-risk features. In summary, our results show the efficacy of RD maintenance and support the safety of maintenance discontinuation in MRD negative patients at 2 years. This trial is registered at ClinicalTrials.gov (NCT02406144) and EudraCT (2014-00055410).