Rituximab/Lenalidomide vs Rituximab/Chemotherapy in Advanced Untreated Follicular Lymphoma
In a phase III RELEVANCE trial reported in The New England Journal of Medicine by Morschhauser et al, no difference in complete response rate or interim progression-free survival was found between rituximab [Rituxan]/lenalidomide [Revlimid] vs rituximab/chemotherapy in newly diagnosed advanced follicular lymphoma. Adverse event profiles differed between the two regimens.
Study Details
In the open-label trial, 1,030 patients from 137 sites in Australia, Belgium, Canada, France, Germany, Italy, Japan, Portugal, Spain, and the United States were randomly assigned between December 2011 and November 2014 to receive rituximab plus lenalidomide (n = 513) or rituximab plus investigator choice of chemotherapy (n = 517). In the chemotherapy group, 372 (72%) received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP); 117 (23%) received rituximab/bendamustine (R-B); and 28 (5%) received rituximab, cyclophosphamide, vincristine, and prednisone (R-CVP). Randomization was stratified by Follicular Lymphoma International Prognostic Index (FLIPI), age (≤ 60 vs > 60 years), and lesion size (≤ 6 vs > 6 cm).
The total treatment duration was 120 weeks for both study groups. Treatment with rituximab plus lenalidomide consisted of 18 cycles of the two drugs followed by rituximab maintenance therapy every 8 weeks for 12 cycles. Treatment with rituximab plus chemotherapy consisted of the rituximab-based regimens followed by maintenance rituximab every 8 weeks for 12 cycles. The primary endpoints were complete response (confirmed or unconfirmed) at 120 weeks and progression-free survival (first interim analysis) on independent review committee assessment in the intent-to-treat population.
In the rituximab/lenalidomide group vs the rituximab/chemotherapy groups, median age was 59 years (16% vs 15% aged > 70 years); 51% were female; and Eastern Cooperative Oncology Group performance status was 0 or 1 in 97%. In the rituximab/lenalidomide group vs the rituximab/chemotherapy group, 94% vs 92% had Ann Arbor stage III or IV disease; 42% vs 38% had bulky disease; disease grade was 1 or 2 in 85% vs 86%; and FLIPI score was 0 or 1 in 15% in both, 2 in 36% vs 37%, and 3 to 5 in 49% vs 48%.
Efficacy Outcomes
After a median follow-up of 37.9 months, confirmed or unconfirmed complete response at 12 weeks was observed in 48% (confirmed in 28%) of the lenalidomide/rituximab group vs 53% (confirmed in 33%) of the rituximab/chemotherapy group (P = .13). On investigator assessment, the rates of confirmed or unconfirmed complete response were 55% vs 58% (P = .38). Overall response rates were 61% vs 65%.
The interim 3-year rate of progression-free survival on independent review was 77% vs 78% (hazard ratio [HR] = 1.10, P = 0.48). On investigator assessment, 3-year progression-free survival was 77% vs 78% (HR = 0.94, P = .63). No signifcant differences between rituximab/lenalidomide and rituximab/chemotherapy were observed in subgroup analysis for either complete response rate or progression-free survival, including analysis by FLIPI scores of 0 to 1, 2, or 3 to 5; age ≤ 60 and > 60 years; or lesion size. Overall survival data were immature at time of analysis; 3-year overall survival was 94% vs 94% (HR = 1.16, 95% confidence interval = 0.72–1.86).
Adverse Events
Adverse events of any grade that were more common in the rituximab/lenalidomide group included cutaneous reactions (43% vs 24%), diarrhea (37% vs 19%), rash (29% vs 8%), abdominal pain (15% vs 9%), myalgia (14% vs 6%), muscle spasms (13% vs 4%), and tumor flare reaction (6% vs < 1%). Adverse events of any grade that were more common in the rituximab/chemotherapy group included anemia (89% vs 66%), fatigue (29% vs 23%), nausea (42% vs 20%), vomiting (19% vs 7%), peripheral neuropathy (16% vs 7%), leukopenia (10% vs 4%), febrile neutropenia (7% vs 2%), and alopecia (9% vs 1%). Rates of thromboembolic events of any grade were similar in the two groups.
Grade 3 or 4 adverse events occurred in 65% of the rituximab/lenalidomide group vs 68% of the rituximab/chemotherapy group. Grade 3 or 4 cutaneous reactions were more common in the rituximab/lenalidomide group, whereas grade 3 or 4 neutropenia was more common in the rituximab/chemotherapy group (50% vs 32%; 31% vs 8% grade 4).
The incidence of infection was higher in the rituximab/chemotherapy group (12% vs 5% any grade, 4% vs 2% grade 3 or 4). Febrile neutropenia requiring hospitalization occurred in 2% of the rituximab/lenalidomide group vs 5% of the rituximab/chemotherapy group, and growth factor was used in 23% vs 68%.
Second primary cancers occurred in 7% vs 10% of patients. Death occurred in 37 patients (23 attributed to lymphoma) vs 29 patients (10 attributed to lymphoma). The death of one patient in each group was considered related to study treatment.
The investigators concluded, “Among patients with previously untreated follicular lymphoma, efficacy results were similar with rituximab plus lenalidomide and rituximab plus chemotherapy (with both regimens followed by rituximab maintenance therapy). The safety profile differed in the two groups.”
The study was funded by Celgene.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
