The combination of lenalidomide with steroid dexamethasone is standard of care in multiple myeloma (MM), but new research shows older patients can be spared the steroids.
Although the combination of lenalidomide and the steroid dexamethasone (Rd) are standard treatment for elderly patients with multiple myeloma (MM), a new study in Blood found that switching older patients to a lower dose of lenalidomide and discontinuing use of dexamethasone was equally safe and effective.
The trial included elderly intermediate-fit patients with newly diagnosed MM to compare Rd induction followed by maintenance of lenalidomide at 10 mg/day without steroids vs the standard continuous Rd treatment.
“Myeloma patients are a very diverse population, including fit patients who may tolerate full-dose treatments, and intermediate-fit and frail patients who are more susceptible to adverse events that may negatively affect the duration and outcome of treatment due to the presence of comorbidities and functional impairments, thus requiring an adapted therapy,” lead author Alessandra Larocca, MD, PhD, of the University of Turin in Italy, said in a statement. “Our study shows, for the first time, that reducing the dose or intensity of treatment is a feasible option and produces similar outcomes as standard dose treatments for intermediate-fit patients.”
Patients were > 65 to ≤ 80 years old, ineligible for autologous stem cell transplantation and considered intermediate-fit based on the International Myeloma Working Group frailty score.
The multicenter, randomized, phase 3 clinical trial involved 33 centers in Italy. A total of 199 patients were randomized to receive Rd for nine 28-day cycles followed by lenalidomide maintenance until progression or intolerance (Rd-R group; n = 101) or continuous Rd for 28-day cycles until progression or intolerance (n = 98).
The primary end point was event-free survival (EFS), and the secondary end points were progression-free survival (PFS), overall survival (OS), response rate, and incidence of dose reductions and discontinuation.
At a median follow-up of 37 months, the median EFS was 10.4 months in the Rd-R group and 6.9 months in the Rd group (HR 0.70; 95% CI, 0.51-0.95, P = .02). The median PFS was 20.2 months in the Rd-R arm and 18.3 months in the Rd arm (HR 0.78; 95% CI, 0.55-1.1, P = .16). The median OS was not reached.
After 9 cycles, there was no difference in median PFS among the patients who remained on therapy.
“Despite no substantial PFS difference between Rd-R vs continuous Rd, a trend towards a better PFS was observed in standard-risk patients treated with Rd-R vs Rd, whereas no difference was observed in high-risk patients, although limited by a lower number of patients,” the authors wrote.
In 26% of Rd-R patients and 20% of Rd patients, there was at least 1 grade ≥ 3 hematologic adverse event (AE). At least 1 grade ≥ 3 non-hematological AE occurred in 33% of Rd-R patients and 43% of Rd patients.
In the Rd-R arm, the rate of lenalidomide discontinuation due to AE was 24% compared with 30% in the Rd arm.
“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 authors concluded.
Larocca A, Bonella F, Gaidano G, et al. Dose/Schedule-Adjusted Rd-R vs Continuous Rd for elderly, intermediate-fit, newly diagnosed multiple myeloma patients. Blood. Published online March 19, 2021. doi:10.1182/blood.2020009507