In a randomized phase 3 clinical trial involving patients with intermediate fitness who had multiple myeloma (MM), treatment with dose/schedule-adjusted lenalidomide plus dexamethasone (Rd) showed feasibility and similar survival outcomes as seen with continuous Rd therapy. Results of this trial were published in the journal Blood.
The multicenter study (ClinicalTrials.gov Identifier: NCT02215980) based in Italy included elderly patients of intermediate fitness who were newly diagnosed with MM. Eligible participants were also ineligible for autologous stem cell transplantation. This trial evaluated the efficacy and feasibility in this patient population of dose/schedule-adjusted course of Rd therapy. Rd for 9 cycles, followed by 10 mg/day lenalidomide maintenance without dexamethasone, was given to patients in the Rd-R arm, while the other study arm received continuous Rd.
The primary study endpoint was event-free survival (EFS). In this study, the definition of EFS involved progression or death from any cause, lenalidomide discontinuation, hematologic grade 4 adverse event (AE), or nonhematologic grade 3 or 4 AE.
A total of 101 patients were in the Rd-R group, and 98 were given continuous Rd. Median patient ages were 75 years with Rd-R and 76 years with continuous Rd (P =.06). In the Rd-R group, the median duration of lenalidomide therapy was 17.3 months, and it was 12.8 months in the continuous Rd group. At a median study follow-up of 37 months, the Rd-R group showed a median EFS of 10.4 months, compared with 6.9 months for continuous Rd (HR, 0.70; 95% CI, 0.51-0.95; P =.02).
The median progression-free survival was 20.2 months for the Rd-R group and 18.3 months for the continuous Rd group (HR, 0.78; 95% CI, 0.55-1.10; P =.16). The 3-year overall survival rate was 74% with Rd-R, and it was 63% with continuous Rd (HR, 0.62; 95% CI, 0.37-1.03; P =.06). The overall response rate was 78% with Rd-R and 68% with Rd (P =.15).
The presence of ≥1 grade 3 or higher hematologic AEs occurred at rates of 26% with Rd-R and 20% with Rd (P =.40). The presence of ≥1 grade 3 or higher nonhematologic AEs occurred at 33% with Rd-R and a rate of 43% with continuous Rd (P =.15). Lenalidomide discontinuations related to AEs occurred in 24% of patients in the Rd-R arm and in 30% in the continuous Rd arm (P =.42).
“An optimization of this combination, sparing steroids and reducing lenalidomide dose after induction (Rd-R), can allow patients to remain on treatment longer, maintaining disease control over time,” the study investigators wrote in their report.
Disclosures: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.
Larocca A, Bonello F, Gaidano G, et al. Dose/schedule-adjusted Rd-R vs continuous Rd for elderly, intermediate-fit patients with newly diagnosed multiple myeloma. Blood. 2021;137(22):3027-3036. doi:10.1182/blood.2020009507