Lenalidomide/rituximab (R2) versus rituximab/placebo efficacy by POD24 status and time to next treatment in patients with relapsed/refractory indolent NHL (AUGMENT)

Relapse is common in indolent lymphoma, and relapse <2y from initial chemoimmunotherapy (ie,POD24) in follicular lymphoma (FL) patient (pts) has been associated with worse prognosis and survival. Objectives here were twofold: To examine the impact of POD24 status in relapsed/refractory (R/R) FL pts and to analyze time to next treatment (TTNT) in R/R FL and marginal zone lymphoma (MZL) pts receiving lenalidomide+rituximab (R2) vs rituximab/placebo (R/placebo). The AUGMENT phase III study evaluated pts with R/R FL gr 1-3a and MZL after >1 prior systemic therapy (not rituximab refractory). Randomization was 1:1 to R2 (lenalidomide PO 20 mg/d, d1-21/28 X12 cycles [c]+rituximab [R] IV 375 mg/m2/wk, c1, d1, 8, 15, 22 and c2-5, d1) and R/placebo (same schedule). The primary endpoint was PFS by 2007 IWG. POD24 was defined post-hoc as PD/relapse <2y from initial an-tilymphoma treatment, which included immuno and/or chemotherapy. Secondary/exploratory analyses were time to next antilymphoma/chemotherapy treatment (TTNLT/TTNCT), response to next treatment, and PFS2. PFS2 was time from randomization to first PD/death (any cause) after next or start of 3rd antilymphoma treatment. As of 22June2018, 178 pts were randomized to R2 (FL, n=147; MZL n=31) and 180 to R/placebo (FL, n=148; MZL, n=32). Median PFS was superior for R2 vs R/placebo (39.4 vs 14.1 mo; HR=0.46; p<0.0001). Of the FL pts, 56 (38%) R2 and 57 (39%) R/placebo pts were POD24. Median PFS was improved in FL pts receiving R2 vs R/placebo, irrespective of POD24 status (HR=0.41 [95% CI, 0.24-0.68] with POD24 and HR=0.43 [95% CI, 0.28-0.65] with no POD24). Best responses were similar in each arm in FL pts with or without POD24. Treatment with R2 (vs R/placebo) reduced the risk of relapse/progression by 59% in FL pts with POD24, and improved both ORR and CR. Similar outcomes were shown for FL pts who relapsed <2y from diagnosis. Median TTNLT, TTNCT, and PFS2 were not reached for R2, and significantly longer than R/placebo (HR=0.54, 0.50, and 0.52, respectively). For R2 (n=49) and R/placebo (n=80) pts receiving next antilymphoma therapy, response was generally higher with R2 (57% ORR 31% CR) vs R/placebo (36% ORR; 16% CR). R2 demonstrated superior efficacy (vs R/placebo) in FL pts, including those with POD24 who are historically associated with worse outcomes. Additionally, these analyses suggest that R2 (vs R/placebo) prolonged TTNT and was associated with longer PFS2, enabling greater response to next therapy.