Quadruplet therapy guided by minimal residual disease (MRD) status can produce deep, durable responses in patients with newly diagnosed multiple myeloma (MM), according to research published in JAMA Oncology.
MRD-guided treatment with elotuzumab plus carfilzomib, lenalidomide, and dexamethasone (Elo-KRd) yielded stringent complete responses (sCRs) and/or MRD negativity in 72% of patients in this study.
The phase 2 study (ClinicalTrials.gov Identifier: NCT02969837) included 46 patients with newly diagnosed MM. At baseline, the patients had a median age of 62 years, 72%, were men, 70% were White, and 48% had high-risk cytogenetics.
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Patients received 12 to 24 cycles of Elo-KRd. The duration of treatment was guided by MRD status after cycles 8 and 12. The primary endpoint was the rate of sCR and/or MRD negativity after 8 cycles of treatment exceeding 30%.
Forty-five patients were evaluable for response. The primary endpoint was met, as 58% of patients achieved sCR and/or MRD negativity at the end of cycle 8.
In all, 38% of patients achieved sCR at the end of cycle 8, 47% had a CR or better, 84% had a very good partial response or better, and 87% had a partial response or better.
The proportion of patients achieving sCR/MRD negativity continued to increase with the number of treatment cycles. Ultimately, 72% of patients had sCR and/or MRD negativity as their best response.
A total of 6 responders went on to autologous stem cell transplant off protocol.
At a median follow-up of 28.7 months, the median progression-free survival (PFS) and overall survival (OS) were not reached in the intent-to-treat population (46 patients).
The estimated 3-year PFS and OS rates were 72% and 78%, respectively, for the entire cohort and 92% and 100%, respectively, for the subset of patients who achieved MRD negativity by cycle 8.
The most common nonhematologic adverse events (AEs) were fatigue (72%), diarrhea (63%), nonpulmonary infections (48%), dyspnea (44%), upper respiratory infections (41%), and peripheral neuropathy (41%). Hematologic AEs included anemia (24%), neutropenia (20%), thrombocytopenia (17%), and lymphopenia (9%).
Cardiac AEs occurred in 26% of patients, and 9% of patients had grade 3 or higher cardiac AEs. One patient had a fatal myocardial infarction on day 1 of cycle 2. Six patients developed COVID-19, and 1 was hospitalized.
“An MRD-adapted design using Elo-KRd without transplant was associated with deep, durable responses and an expected safety profile; this therapeutic approach may decrease treatment exposure over time while maintaining deep responses,” the researchers wrote.
Disclosures: This research was supported, in part, by Amgen and Bristol Myers Squibb. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Reference
Derman BA, Kansagra A, Zonder J, et al. Elotuzumab and weekly carfilzomib, lenalidomide, and dexamethasone in patients with newly diagnosed multiple myeloma without transplant intent. A phase 2 measurable residual disease-adapted study. JAMA Oncol. Published online July 21, 2022. doi:10.1001/jamaoncol.2022.2424
