Lenalidomide/Rituximab Represents an Acceptable Chemo-Free Regimen for Advanced Follicular Lymphoma


Six-year follow-up data showed an overall survival rate of 89% among patients with follicular lymphoma who received either lenalidomide plus rituximab or immunochemotherapy.

Franck Morschhauser, MD, PhD

Franck Morschhauser, MD, PhD

Lenalidomide (Revlimid) plus rituximab (Rituxan) for the frontline treatment of advanced follicular lymphoma (FL) demonstrated a similar efficacy and safety profile to rituximab plus chemotherapy (R-chemo) in a 6-year analysis of the RELEVANCE trial (NCT01650701), according to findings published in the Journal of Clinical Oncology.1

At a median follow-up of 72 months, the overall survival (OS) rate was estimated to be approximately 89% in both groups. Neither cohort reached median OS or progression-free survival (PFS; HR, 1.03; 95% CI, 0.84-1.27; P = .78). In addition, overall responses following disease progression were 61% with lenalidomide/rituximab and 74% with R-chemo. The rate of transformation per year was 0.68% and 0.45% in the 2 groups, respectively, and the rate of secondary primary malignancies were 11% and 13%, respectively (P = .34).

Moreover, no new safety signals emerged in the lenalidomide/rituximab cohort, suggesting that this combination may be an acceptable chemotherapy-free treatment options, noted study authors.

“Both groups maintained very favorable outcomes with similar 6-year PFS rates and excellent 6-year OS rates of 89%,” Franck Morschhauser, MD, PhD, of the University of Lille, and co-investigators wrote in the paper. “Together, these data show that [lenalidomide/rituximab] and R-chemo yield similar durable responses in untreated patients with FL in need of therapy.”

Historically, immunochemotherapy has been considered the frontline gold standard for patients with FL who require systemic therapy; however, this disease has also demonstrated viable responses to nonchemotherapy regimens.

Lenalidomide is an immunomodulatory agent designed to alter the production of cytokine, and consequently increase T-cell costimulation and natural killer cell cytotoxicity. Phase 2 and phase 3 findings have indicated that this agent yields encouraging clinical activity in patients with previously untreated FL.

Previous reports from RELEVANCE documented a similar efficacy profile between lenalidomide/rituximab and rituximab plus chemotherapy; however, information regarding long-term safety and toxicity results with the regimen are limited.

Overall response rates (ORR) in the lenalidomide/rituximab and R-chemo cohorts were 61% and 65%, respectively, and complete response (CR) rates were 48% and 53% (P = .10). Event-free survival and time to next anti-lymphoma treatment were also deemed to be comparable with both treatment regimens.

A total of 206 patients required additional treatment following relapse (lenalidomide, n = 107; R-chemo, n = 99). The ORR was 61% and 59% and the confirmed/unconfirmed CR rates were 37% and 45%.

The number of patients with histologic transformation was 13 vs 11 in the lenalidomide/rituximab and R-chemo groups, respectively. The cumulative incidence of transformation at 6 years in these groups were 4.4% and 3.3%, and the transformation rates per year were 0.68% and 0.45%.

Both regimens had similar safety profiles; 15 patients experienced grade 5 treatment-emergent adverse events (TEAEs; 9 in the lenalidomide/rituximab group and 6 in the R-Chemo group). Of note, among these patients, 1 experienced chronic obstructive pulmonary disease and 2 experienced adenocarcinomas of the colon. Further, between 2017 and 2020, the percentage of patients with second primary malignancies increased from 7% (n = 38) to 11% (n = 57) in the lenalidomide group and from 10% (n = 48) to 13% (n = 67) in the R-chemo group (P = .34).

Throughout the study duration, a total of 8 patients experienced treatment-related deaths—3 of whom were receiving the lenalidomide/rituximab combination and 5 of whom were receiving R-chemo. Patients in the lenalidomide/rituximab combination group reported higher rates of lymphoma-related deaths (29 vs 17, respectively); however, patients in the R-chemo group were more likely to die from other causes (6 vs 13), such as cardiac disorder (0 vs 4).

“The overall safety profile in both groups is consistent with the first interim analysis, and no new safety signals were detected,” study authors noted. “The safety profile of [lenalidomide/rituximab] is distinct from that of R-chemo but manageable. Both treatments were generally well tolerated with the additional follow-up, and treatment/study discontinuation rates were similar.”

Ultimately, this regimen represents an acceptable, chemotherapy-free alternative to R-chemo for patients with advanced or untreated FL, they concluded.


Morschhauser F, Nastoupil L, Feugier P, et al. Six-year results from RELEVANCE: lenalidomide plus rituximab (R2) versus rituximab-chemotherapy followed by rituximab maintenance in untreated advanced follicular lymphoma. J Clin Oncol. 2022;40(28):3239-3245. doi:10.1200/JCO.22.00843

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