Reynolds, Chris

PURPOSE Lenalidomide combined with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) (R2CHOP) in untreated diffuse large B-cell lymphoma (DLBCL) has shown promising activity, particularly in the activated B-cell–like (ABC) subtype. Eastern Cooperative Oncology Group (ECOG)-ACRIN trial E1412 was a randomized phase II study comparing R2CHOP versus R-CHOP in untreated DLBCL. PATIENTS AND METHODS Patients with newly diagnosed DLBCL, stage II bulky-IV disease, International Prognostic Index (IPI) ≥ 2, and ECOG performance status ≤ 2 were eligible and randomly assigned 1:1 to R2CHOP versus R-CHOP for six cycles. Tumors were analyzed using the NanoString Lymph2Cx for cell of origin. The primary end point was progression-free survival (PFS) in all patients with the co-primary end point of PFS in ABC-DLBCL. Secondary end points included overall response rate (ORR), complete response (CR) rate, and overall survival (OS). RESULTS Three hundred forty-nine patients were enrolled; 280 patients (145 R2CHOP and 135 R-CHOP) were evaluable: 94 were ABC-DLBCL, 122 germinal center B-cell–like-DLBCL, 18 unclassifiable, and 46 unknowns. Baseline characteristics were well-balanced between arms, and the median age was 66 (range, 24-92); 70% of patients had stage IV disease; 34%, 43%, and 24% had IPI 2, 3, and 4 or 5, respectively. Myelosuppression was more common in the R2CHOP arm. The ORR and CR rate were 92% and 68% in R-CHOP and 97% ( P = .06) and 73% ( P = .43) in the R2CHOP arm, respectively. The median follow-up was 3.0 years; R2CHOP was associated with a 34% reduction in risk of progression or death versus R-CHOP (hazard ratio [HR], 0.66 95% CI, 0.43 to 1.01) and 3-year PFS of 73% versus 61%, one-sided P = .03, and an improvement in OS (83% and 75% at 3 years; HR, 0.67; one-sided P = .05). The PFS HR for R2CHOP was 0.67 for ABC-DLBCL, one-sided P = .1. CONCLUSION In this signal-seeking study, the addition of lenalidomide to R-CHOP (R2CHOP) improved outcomes in newly diagnosed DLBCL including patients with ABC-DLBCL.

8046 Background: Patients (pts) with relapsed iNHL have limited standard treatment options. The immunomodulatory agent lenalidomide shows enhanced activity with rituximab (ie, R2), which recently reported 39.4-mo median PFS in R/R iNHL pts (AUGMENT; J Clin Oncol. 2019;37:1188). Methods: MAGNIFY is a multicenter, phase IIIb trial in pts with R/R FL gr1-3a, MZL, or MCL (NCT01996865) exploring optimal lenalidomide duration. Lenalidomide 20 mg/d, d1-21/28 + rituximab 375 mg/m2/wk c1 and then q8wk c3+ (R2) are given for 12c followed by 1:1 randomization in pts with SD, PR, or CR to R2 vs rituximab maintenance for 18 mo. Data presented here focus on induction R2 in efficacy-evaluable FL and MZL pts (MCL not included) receiving ≥ 1 treatment with baseline/post-baseline assessments to analyze the primary end point of ORR by 1999 IWG criteria. Results: As of June 16, 2019, 393 pts (81% FL gr1-3a; 19% MZL) were enrolled with a median follow up of 23.7 mo (range, 0.6-57.8) for censored pts (n = 335). Median age was 66 y (range, 35-91), 83% had stage III/IV disease, with a median of 2 prior therapies (95% prior rituximab-containing). ORR was 69% with 40% CR/CRu (Table). Median DOR was 39.0 mo, and median PFS was 40.1 mo. 199 pts (51%) have completed 12c of R2, and 188 (48%) have been randomized and entered maintenance. 139 pts (35%) prematurely discontinued both lenalidomide and rituximab, primarily due to AEs (n = 52, 13%) or PD (n = 45, 11%). Most common all-grade AEs were 48% fatigue, 43% neutropenia, 36% diarrhea, 31% nausea, and 30% constipation. Grade 3/4 AE neutropenia was 36% (9 pts [2%] had febrile neutropenia); all other grade 3/4 AEs occurred in < 7% of pts. Conclusions: R2 is active with a tolerable safety profile in pts with R/R FL and MZL, including rituximab-refractory, double-refractory, and early relapse pts. Clinical trial information: NCT01996865 . [Table: see text]