MRD-Guided Quadruplet Regimen Associated With Deep, Durable Responses in MM

A measurable residual disease (MRD)-adapted study design employing a quadruplet therapy regimen of elotuzumab with weekly carfilzomib, lenalidomide, and dexamethasone (Elo-KRd) without transplant was associated with deep, durable responses and an expected safety profile in newly diagnosed patients with multiple myeloma (MM).

“This therapeutic approach may decrease treatment exposure over time while maintaining deep responses,” wrote Benjamin A. Derman, MD, University of Chicago Medicine, and colleagues in JAMA Oncology.

Patients were enrolled in this multicenter, single-arm, phase 2 study between July 2017 and February 2021. The median follow-up was 29 months, and they employed 12 to 24 cycles of Elo-KRd; consecutive MRD-negative results at 10⁻⁶ by next-generation sequencing after cycles 8 and 12 determined the duration of Elo-KRd. This was followed by Elo-Rd (no carfilzomib) maintenance therapy until disease progression.

The primary study end point was the rate of stringent complete response (sCR) and/or MRD-negativity (10⁻⁵) after 8 cycles of Elo-KRd. Secondary end points included safety, rate of response, MRD status, progression-free survival (PFS), and overall survival (OS). As an exploratory analysis, MRD was assessed using liquid chromatography mass spectrometry (MS) on peripheral blood samples.

A total of 46 patients were enrolled, with a median age of 62 years, and 24% aged over 70 years. High-risk cytogenetic abnormalities were present in 22 (48%) patients.

The rate of sCR and/or MRD-negativity after cycle 8 was 26 (58%) of 45, meeting the predefined statistical threshold for efficacy. Responses deepened over time, with the MRD-negativity rate increasing to 70% and MS-negativity rate increasing to 65%. Dr Derman and colleagues noted the concordance between MRD by next-generation sequencing and MS increased over time.

The most common (>10%) grade 3 or 4 adverse events were lung and nonpulmonary infections, which were 13% and 11%, respectively. There was 1 grade 5 myocardial infarction. The estimated 3-year PFS was 72% overall and 92% for patients with MRD-negativity at cycle 8.

“An MRD-adapted design using elotuzumab and weekly KRd without ASCT showed a high rate of sCR and/or MRD-negativity and durable responses,” Derman and colleagues concluded, “This approach provides support for further evaluation of MRD-guided deescalation of therapy to decrease treatment exposure while sustaining deep responses.”

Source:

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. JAMA Oncology. Published online July 21, 2022. doi:10.1001/jamaoncol.2022.2424