Post-transplant maintenance with carfilzomib, lenalidomide, and dexamethasone (KRd) improves outcomes, when compared with lenalidomide alone, in patients with multiple myeloma (MM), according to research presented at the EHA 2022 Hybrid Congress.
Researchers found that KRd improved progression-free survival (PFS) and minimal residual disease (MRD) negativity. In addition, using MRD status and cytogenetics to guide the continued use of KRd appeared to be effective.
Therefore, risk-adapted, MRD-directed KRd maintenance may represent a new standard of care for this patient population, according to study presenter Dominik Dytfeld, MD, PhD, of Poznań University of Medical Sciences in Poland.
Dr Dytfeld and colleagues conducted the phase 3 ATLAS trial (ClinicalTrials.gov Identifier: NCT02659293) to compare KRd and lenalidomide maintenance in MM patients who had undergone hematopoietic stem cell transplant (HSCT).
The trial included 180 MM patients who had received 2 or fewer prior regimens and had at least stable disease after HSCT. The patients were randomly assigned to receive KRd (n=93) or lenalidomide (n=87) maintenance. Patients in the KRd arm who had standard-risk cytogenetics and achieved MRD negativity after cycle 6 could be switched to lenalidomide alone after cycle 8.
At baseline, the median age was 57 years (range, 32-70) in the KRd arm and 59 years (range, 34-71) in the lenalidomide arm. Less than 10% of patients in each arm had received 2 prior treatment regimens. A majority of patients (88% in the KRd arm and 92% in the lenalidomide arm) had at least a very good partial response at study entry.
At cycle 6, the MRD negativity rate by IMWG criteria was 44% in the KRd arm and 27% in the lenalidomide arm (P =.027).
The median follow-up was 33.8 months. The median PFS was 59 months with KRd and 41.1 months with lenalidomide alone (hazard ratio [HR], 0.56; 95% CI, 0.34-0.93; P =.026).
Among patients with standard-risk cytogenetics, the median PFS was not reached with KRd and was 65.4 months with lenalidomide alone (HR, 0.44; 95% CI, 0.24-0.81; P =.01).
Among patients with standard-risk cytogenetics who achieved MRD negativity at cycle 6, the median PFS was not reached in either arm (HR, 0.23; 95% CI, 0.06-0.86; P =.01).
The median overall survival was not reached in the KRd arm and was 61.8 months in the lenalidomide arm (HR, 0.92; 95% CI, 0.37-2.26; P =.86).
Grade 3 or higher adverse events of interest (in the KRd and lenalidomide arms, respectively) were neutropenia (48% vs 59%), thrombocytopenia (13% vs 7%), infection (15% vs 6%), and cardiovascular toxicity (4% vs 6%).
One treatment-related death was observed in the KRd arm.
Disclosures: This research was sponsored by the University of Chicago. The presenter declared affiliations with Amgen, Celgene/Bristol-Myers Squibb, Janssen, and Takeda.
Dytfeld D, Wróbel T, Jamroziak K, et al. ATLAS: A phase 3 randomized trial of carfilzomib, lenalidomide, and dexamethasone versus lenalidomide alone after stem-cell transplant for multiple myeloma. Presented at EHA 2022; June 9-12, 2022. Abstract S175.