SUBGROUP ANALYSES OF ELDERLY PATIENTS AGED 70 YEARS IN MAGNIFY: A PHASE 3B INTERIM ANALYSIS OF INDUCTION R2 FOLLOWED BY MAINTENANCE IN RELAPSED/REFRACTORY INDOLENT NON-HODGKIN LYMPHOMA

Abstract

Objectives: Lenalidomide combined with rituximab (R2) has shown complimentary clinical activity and is a tolerable regimen in both untreated and relapsed or refractory (R/R) patients (pts) with indolent non-Hodgkin lymphoma. Pts with advanced age at diagnosis are considered to be high risk, supporting post-hoc subgroup analyses by age, with a focus on pts aged ≥ 70 years from the MAGNIFY study. Materials and methods: MAGNIFY is a multicenter, phase 3b trial (NCT01996865) in pts with R/R follicular lymphoma (FL) grades 1–3b, transformed FL (tFL), marginal zone lymphoma (MZL), and mantle cell lymphoma (MCL). Lenalidomide 20 mg on d 1–21 of a 28-d cycle + rituximab 375 mg/m2/wk cycle 1 and then every 8 wk starting with cycle 3 (R2) is given for 12 cycles followed by 1:1 randomization in pts with stable disease, partial response, or complete response/complete response unconfirmed (CR/CRu) to R2 vs rituximab maintenance for 18 mo. The primary end point is progression-free survival (PFS) by 1999 International Working Group (IWG) criteria. Secondary end points include safety, CR rate, duration of response DOR, duration of CR DOCR, time-to-response TTR, time-to-next antilymphoma therapy, and overall survival. Data presented here focus on induction R2 in efficacy-evaluable FL grade 1–3a and MZL pts (FL grade 3b, tFL, and MCL not included) receiving ≥ 1 treatment with baseline/postbaseline assessments. Post-hoc analyses were performed by analyzing data from pts aged ≥ 70 years at time of study entry. Results: As of August 28, 2020, 394 pts have enrolled and 152 (39%) were aged ≥ 70 years. Baseline characteristics including histology, disease status, and prior treatments of pts ≥ 70 and the overall population were similar. Median PFS in the ≥ 70 subgroup was 40.1 months (95% CI, 28.6–NR). Overall response rate (ORR) and CR/CRu were 75% and 39%, with a median duration of response that was not reached (95% CI, 29.4–NR). Efficacy results for the overall population were similar; median PFS = 41.2 mo (95% CI, 38.7–NR), ORR = 75%, CR = 44%, and median DOR = NR (95% CI, 38.6–NR). In pts ≥ 70 the most common (≥ 20%) any-grade treatment emergent adverse events (TEAEs) were fatigue (44%), neutropenia (41%), diarrhea (34%), constipation (34%), and nausea (27%). Neutropenia (35%) was the only grade 3/4 TEAE occurring in > 10% of pts (febrile neutropenia occurred in 3 pts [2%]). TEAEs led to lenalidomide dose reduction in 71 pts (47%) and discontinuation in 42 pts (28%). Eighty-two pts ≥ 70 (54%) completed all 12 cycles of induction treatment, and 75 (49%) have entered the maintenance phase. Sixty-two pts ≥ 70 (41%), prematurely discontinued both lenalidomide and rituximab, due to TEAEs (n = 28; 18%), progressive disease (n = 14; 9%), patient withdrawal (n = 12; 8%), death (n = 4; 3%), and other reasons (n = 4; 3%). Neutropenia was the only TEAE leading to discontinuation of lenalidomide in more than 2 pts (n = 10; 7%). Discussion: Similar to findings in the overall population, R2 treatment in advanced-age pts with R/R FL and MZL resulted in encouraging efficacy, and with close attention to dose reduction there is a tolerable safety profile. Conclusions: These results suggest that R2 should be considered as a therapeutic option for advanced-age pts with R/R FL and MZL.