Randomized, multi-center study of carfilzomib, lenalidomide, and dexamethasone (KRd) with or without daratumumab (D) in patients with newly diagnosed multiple myeloma (NDMM): The ADVANCE clinical trial
Abstract
7503
Background:
The use of modern combination therapy in NDMM patients delivers deep and durable treatment responses independent of transplant status. In the current ADVANCE study (NCT04268498), patients were randomly assigned to receive 8 cycles of carfilzomib-lenalidomide-dexamethasone with or without daratumumab (DKRd vs KRd). Transplants were offered to patients who were minimal residual disease (MRD) positive after 8 cycles. All patients transitioned to lenalidomide maintenance. Primary endpoint was MRD negativity 10^-5 by NGS after up to 8 cycles of combination therapy.
Methods:
306 NDMM patients were randomly assigned 1:1 to receive 8 cycles (28-day cycles) of either DKRd or KRd (D: 1800 mg SC, days 1, 8, 15, and 22 (C1-2), days 1 and 15 (C3-6), day 1 (C7-8); K: 20/56 mg/m2 IV, days 1, 8, and 15; R: 25 mg days 1-21; d: 40/20 mg). Stem cell collection was encouraged after 4 cycles for eligible patients. After completion of cycle 8, patients were evaluated for MRD (ClonoSEQ). Transplant was reserved for MRD-positive patients (post C8). MRD-negative patients transitioned to lenalidomide 10 mg maintenance (D1-21/28). Sustained MRD status was monitored annually. Key eligibility included NDMM with ECOG PS 0-2 and adequate organ function, independent of transplant status. The study was monitored and approved by an independent data safety monitoring committee.
Results:
At 2nd prespecified analysis (data cutoff 01/15/25) demographics and disease characteristics were well…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design. Reported size: 306 participants or records.
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