Rituximab plus Lenalidomide Combination a New Treatment Option for Patients with Follicular Lymphoma
Combination rituximab (Rituxan) and chemotherapy followed by maintenance rituximab has been the standard treatment for advanced-stage, untreated follicular lymphoma; however, most patients will experience a relapse.
Phase 2 clinical trials in treatment-naïve patients with advanced follicular lymphoma had a high response rate to rituximab plus lenalidomide (Revlimid). This led researchers to evaluate the efficacy and safety of rituximab plus lenalidomide compared with rituximab plus chemotherapy in patients with untreated follicular lymphoma (Morschhauser F, et al. N Engl J Med. 2018;379:934-947).
RELEVANCE was a multicenter, international, randomized, open-label, phase 3 study of 1030 patients randomized in a 1:1 ratio to rituximab plus lenalidomide (N = 513) or to rituximab plus chemotherapy (N = 517), followed by rituximab maintenance therapy. The rituximab plus lenalidomide group received lenalidomide 20 mg daily on days 2 through 22 of every 28-day cycle for 6 cycles (or 10 mg daily for 12 cycles if in complete response, or 20 mg daily for 3 to 6 cycles if in partial response). They received rituximab 375 mg/m2 on days 1, 8, 15, and 22 of cycle 1 and on day 1 of cycles 2 through 6. The patients who responded continued to receive rituximab every 8 weeks for 12 cycles.
Patients in the rituximab plus chemotherapy group received the investigator’s choice of 3 regimens—rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone; rituximab and bendamustine (Treanda); or rituximab, cyclophosphamide, vincristine, and prednisone—followed by 12 cycles of maintenance rituximab every 8 weeks for 12 cycles.
The co-primary end points were complete response rate at 120 weeks and progression-free survival (PFS). The median follow-up was 37.9 months.
“Overall, both treatment groups showed good outcomes, and a median has not yet been reached for either progression-free survival or overall survival,” observed the researchers.
The rate of confirmed and unconfirmed complete response rates at 120 weeks was similar between the 2 groups, with 48% in the rituximab plus lenalidomide group and 53% in the rituximab plus chemotherapy group. The investigator-assessed rates were also comparable at 55% and 58%, respectively. The best overall response rates per an independent review committee were 84% and 89%, respectively.
The interim 3-year PFS rates were 77% in the rituximab plus lenalidomide group and 78% in the rituximab-chemotherapy group. The risk for progression or death differed between the 2 arms in the independent review committee assessment (hazard ratio [HR], 1.1; 95% confidence interval [CI], 0.85-1.43) or investigator assessment (HR, 0.94; 95% CI, 0.73-1.22).
A total of 99.8% of the rituximab plus lenalidomide group and 99% of the rituximab plus chemotherapy group had at least 1 adverse event; however, the differences between the 2 groups were noted in the incidence of grade 3 or 4 adverse events. More patients receiving the chemotherapy combination than the lenalidomide combination had grade 3 or 4 neutropenia (50% vs 32%, respectively) and febrile neutropenia (7% vs 2%, respectively), whereas more patients in the rituximab plus lenalidomide group than the chemotherapy group had grade 3 or 4 cutaneous reactions (7% vs 1%, respectively).