POST HOC ANALYSES OF PATIENTS WITH RELAPSED/REFRACTORY MARGINAL ZONE LYMPHOMA WHO RECEIVED LENALIDOMIDE PLUS RITUXIMAB (R2) VS RITUXIMAB/PLACEBO (AUGMENT) (2019)

Introduction: Initial AUGMENT study results in R/R FL grade 1-3a and MZL patients showed significantly improved PFS for lenalidomide plus rituximab (R2) over R/placebo overall and in subgroups, with the exception of the MZL histology. Given the small MZL sample size, post hoc analyses of baseline characteristics and univariate/multivariate analyses of PFS were further examined. Methods: The AUGMENT phase III study randomized patients 1:1 to R2 (lenalidomide PO 20 mg/d, d1-21/28 X12 cycles (c) plus rituximab IV 375 mg/m2/wk c1 and d1 c2-5) or rituximab-placebo (R/placebo; same dosing schedule). The primary endpoint PFS was evaluated by 2007 IWG (without PET). Post hoc Cox regression models evaluated univariate analysis of one risk factor and multivariate analyses for treatment arm and significant risk factors (P<0.05) from the univariate analyses. Results: Of 358 overall patients, 63 (18%) were MZL, including n = 14/16 MALT, n = 9/6 splenic, and n = 8/10 nodal MZL subtypes for R2 and R/placebo arms, respectively. Numerical differences for R2 vs R-placebo, respectively, were ECOG PS 0 (55% vs 72%), age (≥65 y: 68% vs 59%; ≥70 y: 42% vs 38%), refractory to last regimen (13% vs 3%), Ann Arbor stage IV (65% vs 41%), high-risk MALT-IPI (50% vs 19%), elevated LDH (29% vs 19%), B symptoms (13% vs 3%), and high tumor burden per GELF (65% vs 56%). For MZL patients receiving R2 vs R/placebo, respectively, neutropenia (47% vs 16%), pneumonia (3% vs 13%), and leukopenia (10% vs 0) were the most common grade 3/4 AEs. 5 total deaths occurred in the R2 arm (most associated with PD; 2 early deaths occurred at 3 and 13 days post-randomization [1 patient before receiving R2 and 1 patient 2 days after initiating treatment]) and 2 in the R/placebo arm. Despite worse prognostic features, best response was higher, but not statistically significant, with R2 (vs R/placebo): ORR = 65% vs 44% and CR = 29% vs 13%. Median PFS for MZL was 20.2 mo R2vs 25.2 mo R/placebo (HR = 1.00; 95% CI, 0.47-2.13; P = 1.0). Univariate analyses identified several prognostic factors for MZL patients (P<0.05): Ann Arbor stage IV, elevated LDH, and unfit for chemotherapy (Table). Multivariate analyses of PFS showed an adjusted HR of 0.51 (95% CI, 0.20-1.28) favoring R2, similar to the overall PFS HR (HR = 0.46; 95% CI, 0.34-0.63). Conclusions: Overall, these additional analyses in MZL patients suggest that the PFS results were negatively impacted by baseline prognostic factor imbalances and more aggressive disease in the R2 over R/placebo arm. Keywords: lenalidomide; marginal zone lymphoma (MZL); rituximab. Disclosures: Thieblemont, C: Consultant Advisory Role: Cellectis, Kite, Janssen, Roche, Novartis, Bayer; Honoraria: Gilead, Janssen, Novartis; Research Funding: Roche; Other Remuneration: Travel: Roche, Gilead, Janssen. Leonard, J: Consultant Advisory Role: Celgene, Biotest, Sunesis Pharmaceuticals, Bristol-Myers Squibb, Gilead Sciences, Epizyme, Pfizer, Bayer, Genentech/Roche, ADC Therapeutics, MEI Pharma, AstraZeneca, Novartis, Merck, Sutter Medical Group, Morphosys, Beigene, Nordic Nanovector, Bristol-Myers Squibb, United Therapeutics, Karyopharm Therapeutics, Sand; Research Funding: all institutional Celgene, Alliance for Clinical Trials in Oncology, Takeda, Pfizer, National Cancer Institute; Other Remuneration: Travel, Accommodations, Expenses: BeiGene. Trneny, M: Consultant Advisory Role: Takeda, BMS, Incyte, Abbvie, Amgen, Roche, Gilead, Janssen, Celgene, MorphoSys; Honoraria: Janssen, Gilead, Takesa, BMS, Amgen, Abbvie, Roche, MorphoSys, Incyte; Other Remuneration: Travel & Expenses: Gilead, Takeda, BMS, Roche, Janssen, Abbvie. Izutsu, K: Consultant Advisory Role: Bayer, Celgene; Honoraria: Takeda, Chugai Pharma, Eisai, Kyowa Hakko Kirin, Janssen, Ono Pharmaceutical, Gilead Sciences, Abbie, Novartis, MSD, Otsuka; Research Funding: Eisai, Chugai Pharma. Fowler, N: Consultant Advisory Role: Roche/Genentech, TG Therapeutics, Verastem, Bayer, Celgene, Novartis; Research Funding: Roche, Celgene, Gilead Sciences, TG Therapeutics, Novartis, Abbvie, BeiGene. Nowakowski, G: Consultant Advisory Role: Celgene, MorphoSys, Genentech; Research Funding: Celgene, NanoString Technologies, MorphoSys. Pinto, A: Consultant Advisory Role: Servier, Roche, MDS Pharma, BMS; Honoraria: Roche, MDS Pharma, Celgene, Servier, BMS; Research Funding: EDO-Mundipharma; Other Remuneration: Speakers' Bureau: Roche, Travel: Roche, Takeda. Scheinberg, P: Consultant Advisory Role: Novartis, Abbvie, Alexion Pharmaceuticals, Janssen, Celgene; Honoraria: Novartis; Other Remuneration: Speakers' Bureau: Novartis, Pfizer. Flinn, I: Consultant Advisory Role: Abbvie, Seattle Genetics, TG Therapeutics, Verastem; Research Funding: (All institutional): Acerta Pharma, Agios, Calithera Biosciences, Celgene, Constellation Pharmaceuticals, Genentech, Gilead Sciences, Incyte, Infinity Pharmaceuticals, Janssen, Karyopharm Therapeutics, Kite Pharma, Novartis, Pharmacyclics, Portola Pharmaceuticals, Roche, TG Therapeutics, Trillium Therapeutics, Abbvie, ArQule, BeiGene, Curis, FORMA Therapeutics, Forty Seven, Merck, Pfizer, Takeda, Teva, Verastem, Gilead Sciences, Astra Zeneca (AZ), Juno Therapeutics, Unum Therapeutics, MorphoSys AG, Abbvie. Czuczman, M: Employment Leadership Position: Celgene; Stock Ownership: Celgene. Kalambakas, S: Employment Leadership Position: Celgene; Stock Ownership: Celgene, Novartis. Wu, C: Employment Leadership Position: Celgene; Stock Ownership: Celgene. Gribben, J: Consultant Advisory Role: Abbvie, Acerta Pharma/Astra Zeneca, Celgene. Janssen; Honoraria: Abbvie, Acerta Pharma/Astra Zeneca, Celgene. Janssen, Gilead Sciences, Roche/Genentech, TG Therapeutics; Research Funding: Acerta Pharma/Astra Zeneca, Janssen, Celgene.