INDUCTION R2 FOLLOWED BY MAINTENANCE IN PATIENTS WITH RELAPSED/REFRACTORY MANTLE CELL LYMPHOMA: INTERIM ANALYSIS FROM THE PHASE 3B MAGNIFY STUDY

Objectives: The combination of lenalidomide + rituximab (R2) has shown complementary clinical activity and is a tolerable regimen in both untreated and relapsed or refractory (R/R) indolent non-Hodgkin lymphoma (NHL), as well as mantle cell lymphoma (MCL), an uncommon but aggressive form of NHL. The MAGNIFY phase 3 trial previously reported an ORR of 54% in patients with R/R MCL (Sharman J, et al. Hematol Oncol. 2019). Presented here are updated analyses from this trial. Materials and methods: MAGNIFY is a multicenter, phase 3b trial (NCT01996865) in patients with R/R follicular lymphoma (FL) grades 1–3b, transformed FL, marginal zone lymphoma, and 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 patients 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. This analysis evaluates the interim primary endpoint of overall response rate (ORR) by 1999 IWG criteria and safety of R2 induction in patients with MCL in the induction intention-to-treat population. Results: As of August 28, 2020, 73 patients with MCL were enrolled (median age, 70.0 y [range, 51–88]); 89% had stage III/IV disease, and 41% had bulky disease (> 7 cm or > 3 cm ×3 lymph nodes). All patients had received prior rituximab-containing therapy, with 25 (34%) rituximab refractory (progression ≤ 6 mo after last rituximab dose). Seven patients (10%) had received prior ibrutinib. Median follow-up was 31.7 mo for patients still alive. ORR was 51%, with 34% CR rate (CR + CRu). Response rates were similar in patients refractory to rituximab (ORR = 48%, CR/CRu = 32%) and patients not refractory to rituximab (ORR = 52%, CR/CRu = 35%). Median DOR was 31.6 mo; median DOCR was not reached; median TTR was 2.8 mo, and median PFS was 28.0 mo, with 1-year PFS rate of 57%. The most common treatment emergent adverse events (TEAEs) of any grade were neutropenia (51%), fatigue (44%), diarrhea (32%), constipation (28%), cough (28%), dyspnea (26%), and nausea (26%). Grade 3/4 neutropenia was 46%; all other grade 3/4 TEAEs were ≤ 11%. Discussion: R2 is an active and tolerated regimen with durable responses among patients with R/R MCL and mostly naive to Bruton tyrosine kinase inhibitor therapy. Conclusions: These results suggest that R2 should be considered as a therapeutic option for patients with R/R MCL.