Tailored lenalidomide regimen benefits older patients with multiple myeloma
A dose-adjusted lenalidomide regimen that included discontinuation of dexamethasone after 9 months appeared safe and led to similar outcomes as continuous lenalidomide plus dexamethasone among older patients with multiple myeloma.
Results of the randomized phase 3 study were published in Blood.
“We evaluated if switching select older patients to a 10 mg/day dose of lenalidomide [Revlimid, Bristol Myers Squibb] and discontinuing dexamethasone after 9 months would be feasible and safe in intermediate-fit patients — based on the International Myeloma Working Group frailty scale — with newly diagnosed multiple myeloma who were not eligible for transplantation compared with continuous lenalidomide plus dexamethasone,” Alessandra Larocca, MD, PhD, researcher in the division of hematology at University of Turin in Italy, told Healio. “Patients who were no longer taking dexamethasone experienced a significantly longer period without an adverse event or relapse compared with those who continued on the standard lenalidomide-plus-dexamethasone therapy. The tailored approach was also well-tolerated, resulting in fewer adverse effects.”
The study included 199 patients (median age, 76 years; 52% aged 76-80 years) receiving treatment for multiple myeloma at one of 33 medical centers across Italy. Among them, 101 patients received the tailored regimen and 98 received the continuous regimen.
The tailored regimen consisted of nine 28-day induction cycles of 25 mg lenalidomide daily for 21 days and 20 mg dexamethasone on days 1, 8, 15 and 22, followed by 10 mg lenalidomide maintenance daily for 21 days until progression or intolerance. The continuous regimen consisted of the 28-day cycles of lenalidomide and dexamethasone until progression or intolerance.
EFS served as the primary endpoint. Secondary endpoints included PFS, OS, discontinuation of lenalidomide and any grade 4 hematologic or grade 3 to grade 4 nonhematologic adverse events.
Median follow-up was 37 months (range, 27-45).
Results showed median EFS of 10.4 months with the tailored regimen vs. 6.9 months with the continuous regimen (HR = 0.7; 95% CI, 0.51-0.95).
Overall response rate did not differ significantly between the tailored vs. continuous regimen groups (78% vs. 68%), nor did median PFS (20.2 months vs. 18.3 months; HR = 0.78; 95% CI, 0.55-1.1) and 3-year OS (74% vs. 63%; HR = 0.62; 95% CI, 0.37-1.03).
Grade 3 or higher hematologic events occurred among 26% of patients who received the tailored regimen and 20% of patients who received the continuous regimen and included neutropenia (21% vs. 18%) and anemia (9% vs. 7%). Grade 3 or higher nonhematologic adverse events occurred among a greater percentage of patients on the continuous regimen (43% vs. 33%) and included neutropenia (18% vs. 21%), infections (12% vs. 10%) and skin disorders (3% vs. 7%). Central nervous system and constitutional adverse events were more common among the continuous regimen group.
A greater proportion of patients assigned the continuous regimen discontinued lenalidomide (30% vs. 24%) or reduced the dose due to adverse events (62% vs. 45%).
“We expect the results of this study may help to improve and optimize the treatment of elderly patients who may be at greater risk for treatment toxicity and poor survival due to their age or comorbidities,” Larocca said. “Ongoing trials are now evaluating steroid sparing in combination with a monoclonal antibody or the role of frailty-guided treatment.”
For more information:
Alessandra Larocca, MD, PhD, can be reached at University of Turin, Via Giuseppe Verdi, 8, 10124 Torino TO, Italy; email: alelarocca@hotmail.com.
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