Minimal residual disease (MRD)/risk-adapted post-transplant carfilzomib, lenalidomide, and dexamethasone (KRd) therapy demonstrated superior progression-free survival (PFS) compared with lenalidomide (R) maintenance therapy in patients with newly diagnosed multiple myeloma (MM), according to research presented at the 2022 ASCO Annual Meeting. The extended KRd treatment may represent a new standard of care.
The findings come from ATLAS, an international open-label phase 3 randomized trial (ClinicalTrials.gov Identifier: NCT02659293). The researchers recruited newly-diagnosed MM patients who received any induction therapy for up to 12 months followed by single autologous stem cell transplantation (ASCT) and achievement of at least stable disease within 100 days following ASCT and directly compared outcomes of patients treated with post-ASCT KRd to those of patients treated with standard R maintenance.
Patients were randomly assigned to receive either KRd or R and were stratified by post-transplant response (≥ very good partial response [VGPR] vs < VGPR) and cytogenetic risk (standard risk [SR] vs high risk [HR], defined as the presence of t(4;14), t(14;16), or del(17p)).
Patients assigned to the KRd group received 28-day cycles of K 36 mg/m2 (days 1, 2, 8, 9, 15, and 16 for 4 cycles then days 1, 2, 15, and 16 starting at cycle 5), R 25 mg (days 1-21), and D 20 mg (days 1, 8, 15, and 22). Those in the SR group who reached MRD-negativity (according to the International Myeloma Working Group definition) after cycle 6 de-escalated therapy to R alone after cycle 8. All other patients continued KRd through cycle 36 followed by R alone until progression. Patients randomized to R alone received R 10 mg for 3 cycles then 15 mg daily.
The primary objective was progression free survival (PFS) rate. For the presented analysis, the data cutoff date was December 31, 2021.
A total of 180 patients were enrolled on the study, 87 to the R arm and 93 to the KRd arm. Patient characteristics were balanced for median age (KRd and R arms: 58 vs 59 years), >VGPR (88% vs 92%), and HR (23% vs 21%).
After 6 cycles of treatment, 47% of patients in the KRd arm and 29% of patients in the R arm were MRD negative (P =.017). Among those eligible for de-escalation, 34 patients treated with KRd converted to R alone after cycle 8.
At median follow-up duration of 33.8 months, 25% of patients on the KRd arm and 44% of patients on the R arm progressed. The estimated median PFS was 59.0 months with KRd and 41.4 months with R alone (hazard ratio, 0.56; log-rank P =.026). At data cutoff, 90% and 87% of patients were alive in the KRd and R arms, respectively.
The researchers reported that all-grade toxicities were comparable between the arms. The most common grade ≥3 adverse events and those of special interest were neutropenia (KRd, 47%; R, 59%), thrombocytopenia (KRd, 13%; R, 7%), infections (KRd, 15%; R, 6%), cardiovascular toxicities (KRd, 4%; R, 5%), and secondary malignancies (KRd, 2; R, 2). No deaths were consider to be treatment related.
Disclosure: This research was supported by Amgen Pharmaceutical/Biotech Company. Please see the original reference for a full list of disclosures.
Dytfeld D, Wrobel 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 ASCO 2022; June 3-7, 2022. Abstract 8001.