CHICAGO – Lenalidomide plus rituximab (R²) had comparable efficacy versus standard chemoimmunotherapy in patients with previously untreated follicular lymphoma, according to results from a phase 3 trial.

RELEVANCE is the first randomized, phase 3 trial to examine a chemotherapy-free regimen in this setting.

Response and progression-free survival (PFS) results were similar for patients who received R² followed by rituximab maintenance and patients assigned to chemotherapy plus rituximab and rituximab maintenance, in study results presented at the annual meeting of the American Society of Clinical Oncology.

“These results show that lenalidomide plus rituximab, which is a novel immunomodulatory approach, is a potential first-line option for patients with follicular lymphoma that require treatment,” said investigator Nathan H. Fowler, MD, of the University of Texas MD Anderson Cancer Center, Houston.

But since the study was designed as a superiority trial, rather than a noninferiority trial, and it failed to meet its primary endpoint of superior complete remission (CR) or CR unconfirmed (CRu) at 120 weeks, said Bruce D. Cheson, MD, head of hematology at Georgetown University, Washington.

R² had a similar PFS overall and in all major patient subgroups, similar overall survival, less nonhematologic toxicity aside from rash, less neutropenia, and fewer infections despite increased use of growth factors in the chemoimmunotherapy arm, Dr. Cheson said in a presentation commenting on the results. “Therefore, I agree with Dr. Fowler’s conclusion that R² can be considered as an option for the front-line therapy of patients with follicular lymphoma,” Dr. Cheson said.

The RELEVANCE study included 1,030 patients (median age, 59 years) with previously untreated, advanced follicular lymphoma requiring treatment. They were randomized 1:1 to either lenalidomide plus rituximab followed by rituximab maintenance, or R-chemotherapy followed by rituximab maintenance.

For patients randomly assigned to R-chemotherapy, physicians could choose among three standard regimens: rituximab plus bendamustine (R-B), rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), or rituximab plus cyclophosphamide, vincristine, and prednisone (R-CVP).

There was no statistical difference between treatment approaches in CR/CRu at 120 weeks, which was 48% in the R² arm and 53% in the R-chemotherapy arm (P = 0.13). Best CR/CRu also was not statistically different between arms (59% and 67%, respectively), as was best overall response rate (84% and 89%). The 3-year duration of response was 77% in the R2 arm and 74% for R-chemotherapy.

With 37.9 months median follow-up, progression-free survival was “nearly identical” between the two groups, Dr. Fowler said, at 77% for R² and 78% for R-chemotherapy (P = 0.48). The 3-year overall survival was 94% in both the R² and R-chemotherapy arms, though survival data are still immature, Dr. Fowler noted.

Grade 3/4 neutropenia was more common in the R-chemotherapy arm, resulting in higher rates of febrile neutropenia, according to Dr. Fowler, who also noted that rash and cutaneous reactions were more common with R2. About 70% of patients in each arm were able to tolerate treatment, and reasons for discontinuation were “fairly similar” between arms, Dr. Fowler added.

Second primary malignancies occurred in 7% of patients in the R² arm and 10% of the R-chemotherapy arm.

The study was sponsored was Celgene and the Lymphoma Academic Research Organisation. Dr. Fowler reported disclosures related to Abbvie, Celgene, Janssen, Merck, and Roche.

SOURCE: Fowler NH et al. ASCO 2018, Abstract 7500.

Chemo-free regimen appears viable in previously untreated FL