FDA Approves Revlimid/Rituxan Combo for Indolent Non-Hodgkin Lymphoma

The Food and Drug Administration (FDA) has approved the combination regimen of Revlimid (lenalidomide) plus Rituxan (rituximab), also known as the R² regimen, for use in patients with previously-treated follicular lymphoma and marginal zone lymphoma.

“Nearly 15 years following the initial FDA approval, Revlimid continues to demonstrate benefits for new patient populations,” Dr. Jay Backstrom, chief medical officer and head of Global Regulatory Affairs for Celgene, the manufacturer of Revlimid, said in a statement. “Revlimid in combination with rituximab leads to immune-mediated treatment effects and represents a chemotherapy-free treatment option that can help patients with previously treated follicular lymphoma and marginal zone lymphoma delay disease progression.”

The agency based its decision on results from the double-blind, phase 3 AUGMENT trial, which included 358 patients with relapsed/refractory follicular lymphoma (295 patients) or marginal zone lymphoma (63 patients) in need of treatment. Patients had to have received at least one prior chemotherapy, immunotherapy or chemoimmunotherapy regimen and could not be refractory to treatment with Rituxan.

Patient characteristics at baseline were well balanced overall between the two arms: about 60% of patients were aged 60 or older; over 70% of patients had advanced-stage disease at study entry; about 50% of patients had high tumor burden; and around 83% of patients in each arm had follicular lymphoma, with the remaining 17% having marginal zone lymphoma.

In the trial, the combination regimen reduced the risk of disease progression or death by 54% compared with Rituxan alone. At a median follow-up of 28.3 months, the median progression-free survival (or time from treatment to disease worsening) was 39.4 months with the combination regimen versus 14.1 months with Rituxan alone.

By investigator assessment, the median progression-free survival was 25.3 months versus 14.3 months, respectively. Overall response rate was also significantly improved with the combination: 78% versus 53%, respectively. Of note, the 78% overall response rate included a 44% complete response rate and a 34% partial response rate.

In addition, the progression-free survival benefit with Revlimid and Rituxan was sustained across almost all prespecified subgroups, regardless of age, disease histology, whether or not they had prior Rituxan, number of prior regimens, time since last anti-lymphoma therapy, geographic region where treatment was received, chemoresistance status or tumor burden status.

The one exception in which the progression-free survival advantage in a subgroup was not consistent with the overall population was the subgroup of patients with marginal zone lymphoma. “This relates to the fact that there were roughly 30 patients in each arm with (marginal zone lymphoma), which limits these comparisons,” lead study author Dr. John Leonard, associate dean for clinical research and Richard T. Silver Distinguished Professor of Hematology and Medical Oncology at Weill Cornell Medicine and New York-Presbyterian Hospital in New York City, said when presenting the data at the 2018 ASH Annual Meeting.

Overall survival data across the entire population showed that at a median follow-up of 28.3 months. The two-year overall survival rate was 93% for Revlimid and Rituxan and 87% for Rituxan alone.

In a prespecified subgroup analysis of patients with follicular lymphoma, at a median follow-up of 28.3 months, the two-year overall survival rate was 95% for the combination regimen and 86% for Rituxan alone.

Thirty percent of patients in the Revlimid and Rituxan arm discontinued treatment early compared with 39% of patients in the placebo arm. The primary cause of discontinuation was disease progression, at 12% in the Revlimid and Rituxan arm versus 30% in the control arm. Side effects led to discontinuation in 8% of the Revlimid and Rituxan group versus 4% of the placebo group. Among patients receiving Revlimid, 66% had at least one side effect-related dose interruption.

“The main grade 3/4 (side effect) difference (between the 2 arms) in (side effects was) in neutropenia.” However, the neutropenia generally did not result in febrile neutropenia, with only 3% of patients in the Revlimid and Rituxan arm having febrile neutropenia.

Also of note, six patients in the Revlimid and Rituxan arm and 10 patients in the placebo arm had secondary malignancies. “Venous and arterial thromboembolic (side effects) were relatively low and similar in both arms,” said Leonard.

This article originally appeared on OncLive as “FDA Approves Lenalidomide/Rituximab for Indolent Non-Hodgkin Lymphoma.”