Poorer Outcomes With Rituximab + Chemo in Heavier Patients, Older Men With Follicular Lymphoma CCO Independent Conference Highlights of the 2015 ASCO Annual Meeting* May 29 - June 2, 2015 *CCO is an independent medical education company that provides state-of-the-art medical information to healthcare professionals through conference coverage and other educational programs. This program is supported by educational grants from AstraZeneca, Bayer, Bristol-Myers Squibb, Celgene Corporation, Genentech, Incyte, and Novartis.

Rituximab in NHL: Pt Factors May Affect Rituximab Pharmacokinetics In aggressive NHL, sex, age, body weight affect rituximab pharmacokinetics may influence outcomes[1,2] Current analysis evaluated whether these factors affected clinical outcomes in pts receiving rituximab-based initial therapy for indolent NHL Based on retrospective analysis of consecutive group of pts treated at Cleveland Clinic NHL, non-Hodgkin’s lymphoma. 1. Müller C, et al. Blood. 2012;119:3276-3284. 2. Pfreundschuh M, et al. Blood. 2014;123:640-646.

Rituximab in NHL: Study Design Pts receiving rituximab-containing initial therapy for indolent NHL from 1997 to 2014 N = 303; 3 cohorts Rituximab only (n = 119) Rituximab + chemotherapy (n = 120) R-chemo followed by R maintenance (n = 64) Cohorts assessed based on FL (n = 184) or non-FL (n = 199) histology EFS: treatment Day 1 until relapse, progression, histologic transformation, loss of follow-up, start of second-line therapy, or death EFS, event free survival; FL, follicular lymphoma; NHL, non-Hodgkin’s lymphoma. Sawalha Y, et al. ASCO 2015. Abstract 8567.

Rituximab in NHL: Baseline Characteristics No significant differences in age, weight, BSA Parameter R R-Chemo R-Chemo  R P Value Median age, yrs (range) 63 (31-98) 60 (28-89) 63 (29-86) .073 Median weight, kg (range) 83 (43-173) 79 (43-156) 77 (51-115) .11 Median BSA, m2 (range) 2.0 (1.4-3.0) 1.9 (1.4-2.8) 1.9 (1.5-2.4) .10 Male, % 48.7 53.3 46.9 .65 Median time since diagnosis, mos (range) 2.7 (0-149) 1.3 (0.1-108) 1 (0.1-94) < .001 Pts with an event, % 62 51 28 Median follow-up for pts without event, yrs (range) 2.6 (0.18-11.0) 3.9 (0.44-8.3) 3.0 (0.62-8.8) .26 BSA, body surface area; NHL, non-Hodgkin’s lymphoma; R, rituximab. Sawalha Y, et al. ASCO 2015. Abstract 8567.

Rituximab in NHL: R-Chemo Cohort EFS 1.00 R-Chemo 1.00 FL in the R-Chemo Cohort Elderly females Young females Elderly males Young males Elderly females Young females Elderly males Young males 0.75 0.75 EFS 0.50 EFS 0.50 0.25 0.25 Yr 3 6 9 Yr 3 6 9 1.00 R-Chemo 1.00 FL in the R-Chemo Cohort EFS, event-free survival; NHL, non-Hodgkin’s lymphoma; R, rituximab. Weight ≤ 81.8 kg Weight > 81.8 kg Weight ≤ 81.8 kg Weight > 81.8 kg 0.75 0.75 0.50 0.50 EFS EFS 0.25 0.25 Yr 3 6 9 Yr 3 6 9 Sawalha Y, et al. ASCO 2015. Abstract 8567. Reprinted with permission.

Rituximab in NHL: R-Chemo Cohort Outcomes In univariate analysis, heavier pts had worse outcomes, older females had better outcomes among R-chemo–treated pts with FL Effect not observed in R-only or R-chemo  R cohorts HR for EFS in Pts Receiving R-Chemo (95% CI; P Value) Characteristic All Pts (n = 120) FL (n = 81) Non-FL (n = 39) Weight ≥ 81.8 kg 1.81 (1.1-2.99; .02) 2.40 (1.31-4.40; .005) 1.05 (0.41-2.66; NS) BSA ≥ 2 m2 1.44 (0.87-2.38; 1.90 (1.04-3.48; .037) 0.84 (0.32-2.18; Females aged 65 yrs or older 0.34 (0.12-0.93; .035) 0.21 (0.05-0.88; .033) 0.71 (0.15-3.27; BSA, body surface area; EFS, event-free survival; FL, follicular lymphoma; NHL, non-Hodgkin’s lymphoma; NS, not significant; R, rituximab. Sawalha Y, et al. ASCO 2015. Abstract 8567.

Rituximab in NHL: Combined Cohort Outcomes In univariate analysis, weight, BSA, sex, associated with outcomes in combined cohorts In multivariate analysis of all pts, weight significantly associated outcome (HR: 1.55; P = .031) HR for EFS for All Cohorts (95% CI; P Value) Characteristic All Pts (N = 303) FL (n = 184) Non-FL (n = 119) Weight ≥ 81.8 kg 1.52 (1.1-2.09; .01) 1.65 (1.08-2.5; .019) 1.31 (0.79-2.15; NS) BSA ≥ 2 m2 1.39 (1.01-1.91; .041) 1.45 (0.95-2.21; 1.24 (0.75-2.03; Female 0.73 (0.53-1.01; 0.88 (0.58-1.35; 0.59 (0.35-0.995; .048) BSA, body surface area; EFS, event-free survival; FL, follicular lymphoma; NHL, non-Hodgkin’s lymphoma; NS, not significant. Sawalha Y, et al. ASCO 2015. Abstract 8567.

Rituximab in NHL: Conclusions In pts with indolent lymphoma (particularly FL), outcomes among pts receiving R-chemo worse in heavier pts, better in older females vs older males Same effect not observed in R alone or R-chemo  R cohorts Investigator conclusions Pt weight shown to negatively affect outcomes in pts treated with R- chemo Likely due to faster rituximab clearance Hypothesis: higher rituximab levels (weekly and/or maintenance) exceed therapeutic threshold, counteract negative impact of pt weight Subsets of pts with FL may receive suboptimal doses of rituximab FL, follicular lymphoma; NHL, non-Hodgkin’s lymphoma; R, rituximab. Sawalha Y, et al. ASCO 2015. Abstract 8567.

Go Online for More CCO Coverage of ASCO 2015! Short slidesets of all the key data Additional CME-certified analyses with expert faculty commentary on all the key studies in: Gastrointestinal cancers Genitourinary cancer Hematologic malignancies Immunotherapy Lung cancer clinicaloptions.com/oncology