2018 ASCO: Lenalidomide Plus Rituximab vs Rituximab Plus Chemotherapy in Previously Untreated Follicular Lymphoma
Results from RELEVANCE, a phase III, randomized, open-label, international clinical study conducted in partnership with the Lymphoma Academic Research Organisation (LYSARC), were presented by Fowler et al at the 2018 ASCO Annual Meeting (Abstract 7005).
This study evaluated the investigational regimen of lenalidomide (Revlimid) plus rituximab (Rituxan), or R2, followed by R2 maintenance, compared to the standard-of-care treatment of rituximab plus chemotherapy (R-chemo: R-CHOP [rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone], R-bendamustine, or R-CVP [rituximab plus cyclophosphamide, vincristine, and prednisone) followed by rituximab maintenance in patients with previously untreated follicular lymphoma.
Major Findings
Investigators found that treatment with a chemotherapy-free R2 regimen offered numerically similar efficacy results for the primary endpoints of progression-free survival and complete response or unconfirmed complete response at 120 weeks with a different safety profile than treatment with the conventional R-chemo standard. As previously disclosed, the study did not achieve the primary endpoints of superior progression-free survival and complete response/unconfirmed complete response.
“These findings provide important insight into the efficacy and safety of a chemotherapy-free regimen in patients with previously untreated follicular lymphoma and represent an important step forward in understanding possible treatment options for these patients,” said Nathan Fowler, MD, Associate Professor, Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center.
More About RELEVANCE
RELEVANCE is the first multicenter, international, open-label, randomized phase III clinical trial of the chemotherapy-free combination immunotherapy R2 vs R-chemo followed by rituximab maintenance in previously untreated advanced follicular lymphoma. The study was conducted by Celgene in the United States and Japan and by LYSARC in the rest of the world at 136 centers in 10 countries.
The trial evaluated 1,030 patients with advanced follicular lymphoma who had not received prior treatment and were deemed to require treatment per Groupe d'Etude des Lymphomes Folliculaires criteria. Patients received treatment for 120 weeks and were randomized to receive either R2 or R-chemo treatment. The median age of the patients was 59 years.
The R2 arm received lenalidomide plus rituximab on the following dosing schedules: lenalidomide at 20 mg on days 2 to 22 every 28 days for up to 6 cycles. Patients with a complete response after 6 cycles then received lenalidomide at 10 mg on days 2 to 22 every 28 days for 12 cycles. Patients with a partial response after 6 cycles continued to receive lenalidomide at 20 mg for 3 to 6 cycles until they achieved a complete response or unconfirmed complete response, at which time they then received lenalidomide at 10 mg on days 2 to 22 of every 28-day cycle for up to 9 or 6 cycles, respectively. Patients who remained in partial response after the additional 6 cycles received lenalidomide at 10 mg for a total of 18 cycles. Rituximab at 375 mg/m2 was administered on days 1, 8, 15, and 22 of cycle 1 and day 1 of cycles 2 to 6; 8 weeks later, responding patients continued with rituximab at 375 at mg/m2 every 8 weeks for 12 cycles.
The R-chemo arm received one of the following: rituximab/CHOP (72%), rituximab/CVP (5%), or rituximab/bendamustine (23%). Seven to 8 weeks later, responding patients continued with rituximab at 375 mg/m2 every 8 weeks for 12 cycles.
The coprimary efficacy endpoints of the study were complete response/unconfirmed complete response at 120 weeks and progression-free survival during the preplanned analysis (final analysis of complete response/unconfirmed complete response and interim analysis of progression-free survival). An analysis of the findings found that 48% of patients in the R2 arm and 53% of those receiving R-chemo maintained complete response/unconfirmed complete response 120 weeks after randomization, with a 3-year estimated interim progression-free survival rate of 77% and 78%, respectively (hazard ratio [HR] = 1.10, 95% confidence interval [CI] = 0.85–1.43; P = .48).
Preliminary overall survival, one of the study's secondary endpoints, showed a 3-year survival rate of 94% in both treatment arms. Other secondary endpoints included number of patients with adverse events, time to treatment failure, event-free survival, time to next antilymphoma treatment, time to next chemotherapy treatment, overall response rate at 120 weeks based on International Working Group 1999 criteria, and health-related quality of life as measured by the EORTC QLQ-C30.
The majority of patients in both arms completed treatment (69% R2 and 71% R-chemo). The most common grade 3/4 treatment-related adverse events in both arms were neutropenia (32% R2 vs 50% R-chemo), febrile neutropenia (2% R2 vs 7% R-chemo), and cutaneous events (7% R2 vs 1% R-chemo). Second primary malignancies were reported in 7% R2 and 10% R-chemo patients, and grade 5 adverse events were 1% in both treatment arms.
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