Frontline Chemo-Free Combination Shows Activity in Frail Older Patients With DLBCL

The chemo-free combination of rituximab and lenalidomide in frontline therapy is feasible and has moderate activity in older patients with diffuse large B-cell lymphoma (DLBCL) who have a frail geriatric assessment profile, according to research published in Blood.

“Compared with those of their younger counterparts, the outcomes of older patients [with DLBCL] remain dismal because of age-related conditions and their reduced tolerance to treatment side effects [of anthracycline-containing regimens],” the study authors explained in their report. 

Researchers conducted a 2-stage single-arm trial, sponsored by the Fondazione Italiana Linfomi (FIL_ReRi study; ClinicalTrials.gov Identifier: NCT02955823), to investigate the activity and safety of the chemo-free combination of rituximab and lenalidomide in untreated patients ≥70 years of age with DLBCL considered frail according to a simplified geriatric assessment tool. Enrollment took place between January 2017 and June 2021.

For induction treatment, patients received a maximum of 6 cycles of oral lenalidomide (20 mg) on days 2-22 and intravenous rituximab (375 mg/m²) on day 1 of a 28-day cycle. Response was assessed after cycles 4 and 6. Patients who achieved partial response or complete response (CR) at cycle 6 received maintenance lenalidomide (10 mg/d) on days 1-21 until a maximum of 12 cycles total or until progression or unacceptable toxicity. 

The primary endpoints were the overall response rate (ORR) after cycle 6 and the rate of grade 3 or 4 extrahematologic toxicity according to the National Cancer Institute Common Terminology Criteria. 

The study included 65 patients (53.9% female), with a median age of 83 years (range, 70-91). After cycle 6, the ORR was 50.8% (95% CI, 38.1-63.4), with a 27.7% CR rate. After a median follow-up of 24 months, the median progression-free survival was 14 months (95% CI, 6.8 months to not reached), and the duration of response was 64% (95% CI, 42.1-80.1). 

Overall, 34 of 65 patients (52.3%) experienced at least 1 grade ≥3 extrahematologic toxicity. Of the 50 grade ≥3 extrahematologic events experienced among these patients, 41 (82%) were grade 3, 4 (8%) were grade 4, and 5 (10%) were grade 5.

“The activity of the [rituximab and lenalidomide] combination was observed in a significant proportion of cases, warranting further exploration of chemo-free approaches in this setting, and our results could constitute a new benchmark for future studies,” the study authors concluded.

Limitations of the study included the formally negative ORR result as the minimum number of responses required by the statistical plan to confirm the alternative hypothesis was not reached, the initial unplanned collection of certain biological data — notably cell-of-origin profiling — and lack of strict follow-up monitoring using computed tomography due to the frailty status of the patients.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, or device companies. Please see the original reference for a full list of authors’ disclosures.  

Reference

Gini G, Tani M, Tucci A, et al. Lenalidomide plus rituximab for the initial treatment of frail older patients with DLBCL: the FIL_ReRi phase 2 study. Blood. 2023;142(17):1438-1447. doi:10.1182/blood.2022019173

This article originally appeared on Hematology Advisor