A dexamethasone-sparing treatment strategy is safe and effective for frail patients with newly diagnosed multiple myeloma (MM), according to researchers.
The team found that a regimen of daratumumab and lenalidomide with 2 cycles of low-dose dexamethasone (DR) was more effective than a regimen of lenalidomide and continuous low-dose dexamethasone (Rd). Grade 3 or higher toxicities were generally more common with DR, but rates of treatment discontinuation were similar with each regimen.
These results were presented at the 2022 ASH Annual Meeting by Salomon Manier, MD, PhD, of Lille University Hospital in France.
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The phase 3 trial (ClinicalTrials.gov Identifier: NCT03993912) enrolled patients with newly diagnosed MM who were 65 years of age or older and had an IFM frailty score of 2 or higher.
The patients were randomly assigned to receive DR (n=199) or Rd (n=94). Baseline characteristics were well balanced between the arms.
Patients in the Rd arm received lenalidomide at 25 mg daily on days 1-21 of each 28-day cycle and dexamethasone at 20 mg once a week. Patients in the DR arm received lenalidomide at 25 mg daily on days 1-21, dexamethasone at 20 mg weekly for 2 cycles, and daratumumab at 1800 mg weekly for 8 weeks, every other week for 16 weeks, and every 4 weeks thereafter. Patients in both arms were treated until disease progression or unacceptable toxicity.
The overall response rate was higher in the DR arm than in the Rd arm — 96% and 85%, respectively (P =.001). The rate of very good partial response was 64% and 43%, respectively.
Patients in the DR arm had deeper responses at all time points. The rate of very good partial response was 41% with DR and 26% with Rd at 4 months, 68% with DR and 48% with Rd at 8 months, and 71% with DR and 55% with Rd at 12 months.
The rate of minimal residual disease negativity was 10% in the DR arm and 3% in the Rd arm (P =.012).
Grade 3 or higher adverse events (AEs) were more common in the DR arm than in the Rd arm — 82% and 68%, respectively (P =.01). This was primarily due to hematologic AEs. The rate of grade 3 or higher neutropenia was 46% in the DR arm and 18% in the Rd arm (P <.0001). The rates of grade 3 or higher anemia were 11% and 2%, respectively (P =.01).
The rate of grade 3 or higher infections was 13% in the DR arm and 18% in the Rd arm (P =.29). The percentage of patients who discontinued treatment due to AEs was 14% with DR and 16% with Rd (P =.65).
“This preliminary data on a dexamethasone-sparing strategy is encouraging for a frail population of patients,” Dr Manier said. He added that the analysis of progression-free survival is ongoing.
Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Reference
Manier S, Corre J, Hulin C, et al. A dexamethasone sparing-regimen with daratumumab and lenalidomide in frail patients with newly-diagnosed multiple myeloma: Efficacy and safety analysis of the phase 3 IFM2017-03 trial. Presented at ASH 2022. December 10-13, 2022. Abstract 569.
