TOPLINE

A phase 3 trial found that in older patients with relapsed/refractory (R/R) follicular lymphoma who had responded to salvage immunochemotherapy, adding lenalidomide to rituximab maintenance therapy did not significantly improve 2-year progression-free survival (PFS) compared with rituximab alone, although a numerical benefit was seen; the combination regimen was also associated with a higher incidence of adverse events. Notably, a subgroup analysis suggested a favorable benefit-risk balance with the combination regimen in patients younger than 70 years.

METHODOLOGY

• R/R follicular lymphoma remains difficult to treat in older or transplant-ineligible patients who have limited durable options after prior anti-CD20 therapy. Although regimens such as rituximab-lenalidomide have shown promise in prior studies, their role as maintenance therapy for patients with R/R follicular lymphoma previously exposed to immunochemotherapy has not been defined.
• To evaluate whether the addition of lenalidomide to rituximab improves the efficacy of standard rituximab maintenance, researchers conducted a multicenter, phase 3 randomized trial of 152 older or transplant-ineligible patients (median age, 71 years) with R/R, grade 1/2 or 3A follicular lymphoma in advanced stage who required treatment after one or two previous lines of rituximab-containing regimens.
• Overall, 129 patients (85%) achieved an overall response after induction and were randomly assigned to rituximab (n = 65; every 90 days for eight cycles) or rituximab plus lenalidomide (n = 64; rituximab on the same schedule plus lenalidomide on days 1-21 every 28 days for 24 cycles).
• The primary outcome was 2-year PFS from randomization; secondary outcomes included overall survival (OS), time to next treatment, and toxicity. The median follow-up duration was 68 months.
• Most patients received bendamustine plus rituximab as induction treatment (83%), followed by rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (7%), rituximab plus cyclophosphamide, vincristine, and prednisone (10%), and rituximab plus fludarabine, mitoxantrone, and dexamethasone (1%). Overall, 86% of patients received four cycles of induction therapy, whereas 14% received a total of six cycles before randomization.

TAKEAWAY

• Among patients who were randomized, the 2-year PFS was numerically higher in the combination arm than in the monotherapy arm (73% vs 64%; hazard ratio [HR], 0.73), but the difference was not statistically significant (P = .183).
• The 2-year OS was numerically lower with combination therapy than with monotherapy (80% vs 89%; HR, 1.12; P = .72), whereas time to next treatment favored combination therapy, with a lower 2-year probability of starting salvage treatment (6.7% vs 22.4%; HR, 0.60; P = .124); neither difference reached statistical significance, indicating no clear survival or treatment-free advantage with the addition of lenalidomide.
• In an unplanned subgroup analysis, combination therapy appeared to provide greater benefit than monotherapy in patients younger than 70 years — with improved 2-year PFS (96% vs 69%; HR, 0.32; interaction P = .042) and 2-year OS (100% vs 91%; HR, 0.29; interaction P = .056).
• Combination therapy resulted in more frequent grade 3/4 adverse events than monotherapy, including neutropenia (40.6% vs 11.5%; P < .001) and gastrointestinal disorders (9.4% vs 0%; P = .032). Fatal treatment-emergent adverse events were reported in nine patients (7%), including five in the monotherapy arm and four in the combination arm.

IN PRACTICE

"These findings support a personalized approach to maintenance therapy in R/R FL [follicular lymphoma]. Further studies are warranted to validate these results and optimize R2 [rituximab and lenalidomide]-based maintenance strategies by integrating novel approaches to enhance efficacy while minimizing toxicity," the study authors wrote. 

SOURCE

The study, led by Barbara Botto, MD, of Azienda Ospedaliero-Universitaria Città della Salute e della Scienza in Turin, Italy, was published online in Blood Advances.

LIMITATIONS

The study had several limitations, including the extended enrollment period, the open-label design, the absence of centralized radiologic review to confirm response, a lower lenalidomide dose than that used in other rituximab and lenalidomide trials, and a potentially overly optimistic projection of the expected PFS improvement between treatment arms.

DISCLOSURES

The study was partially supported by grants from Fondazione Piemontese per la Ricerca sul Cancro and the Italian Ministry of Health. Celgene/Bristol Myers Squibb provided lenalidomide and partial funding. Several authors reported receiving consulting fees and speakers bureau honoraria, as well as having other ties with various pharmaceutical companies, including AbbVie, AstraZeneca, BeiGene, Gilead, Incyte, Janssen, Roche, Takeda, and others. Full disclosures are reported in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.