Recent clinical trial results suggested similar efficacy for thalidomide (T), compared with lenalidomide (R), in combination with carfilzomib (K) and dexamethasone (d) in treatment of transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM). Trial results were presented at the EHA 2022 Hybrid Congress by Heinz Ludwig, MD, of the Wilhelminen Cancer Research Institute in Vienna, Austria, and colleagues.
The phase 2 AGMT-MM02 trial (ClinicalTrials.gov Identifier: NCT02891811) contained 2 randomized treatment arms for 9 cycles of induction therapy, with 1 arm featuring T plus Kd (KTd) and the other arm featuring R plus Kd (KRd). Following induction, patients were again randomized for a maintenance period, which consisted of either 12 cycles of K maintenance therapy or observation. Patients in this trial were >65 years of age, had NDMM, and were transplant ineligible, in addition to other eligibility criteria. The primary study objective was to show noninferiority in response rates for KTd, relative to KRd.
A total of 123 patients were randomized in the induction stage of the trial, with 62 patients in the KTd arm and 61 patients in the KRd arm. In the maintenance stage, 79 patients were randomized, with 39 patients receiving K maintenance and 40 patients undergoing observation. The median follow-up times were 31.8 months for the KTd arm and 29.0 months for the KRd arm.
The overall response rate was 93.3% in the KTd arm, and it was 88.1% in the KRd arm. A very good partial response or better was seen in 77.4% of patients in the KTd arm and in 65.6% of the KRd arm.
The median progression-free survival (PFS) time did not significantly differ between arms, occurring at 25.3 months for the KTd group and at 34.4 months for the KRd group (P =.853). The median overall survival (OS) time was not reached in the KTd arm, and it was 52.2 months for the KRd arm (P =.463).
The minimal residual disease (MRD) status, assessed at the 10-6 threshold, was negative in 48.3% of 60 patients who were evaluated at the end of 9 months of induction. MRD negativity was seen in 39% of patients in the KTd arm and in 59% of patients in the KRd arm, but this difference was not significant (P =.126).
Toxicity profiles differed between treatment arms. Among grade 1 and 2 nonhematologic adverse events (AEs), the KTd arm reported more edema, peripheral neuropathy, neurologic disorders, and others. The KRd arm reported slightly more grade 1 or 2 diarrhea and rash. Grade 3 or 4 cardiac disorders were reported in 6.5% of patients in the KTd arm and in 11.5% of the KRd arm. There were 4 study-related deaths reported.
The study investigators concluded that KTd was noninferior to KRd in this study of transplant-ineligible patients at least 65 years of age with NDMM, with high response rates seen in both treatment arms and similar PFS and OS rates with each. Toxicity profiles differed between treatments, but the investigators considered most AEs to be of grades 1 and 2.
Disclosures are not available for this presentation.
Ludwig H, Melchardt T, Sormann S, et al. Randomized comparison between KRd and KTd induction, followed by K maintenance or observation in transplant non-eligible patients with NDMM (AGMT-MM02 trial). Presented at EHA 2022; June 9-12, 2022. Abstract S179.