1. 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.

2. 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:
2. Pfreundschuh M, et al. Blood. 2014;123:

3. 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 Abstract 8567.

4. 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 ( )
1.9 ( )
1.9 ( )
.10
Male, %
48.7
53.3
46.9
.65
Median time since diagnosis, mos (range)
2.7 (0-149)
1.3 ( )
1 (0.1-94)
< .001
Pts with an event, % 62 51 28
Median follow-up for pts without event, yrs (range)
2.6 ( )
3.9 ( )
3.0 ( )
.26
BSA, body surface area; NHL, non-Hodgkin’s lymphoma; R, rituximab.
Sawalha Y, et al. ASCO Abstract 8567.

5. 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 Abstract Reprinted with permission.

6. 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 ( ;
.02)
2.40 ( ;
.005)
1.05 ( ;
NS)
BSA ≥ 2 m2
1.44 ( ;
1.90 ( ;
.037)
0.84 ( ;
Females aged 65 yrs or older
0.34 ( ;
.035)
0.21 ( ;
.033)
0.71 ( ;
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 Abstract 8567.

7. 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 ( ;
.01)
1.65 ( ;
.019)
1.31 ( ;
NS)
BSA ≥ 2 m2
1.39 ( ;
.041)
1.45 ( ;
1.24 ( ;
Female
0.73 ( ;
0.88 ( ;
0.59 ( ;
.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 Abstract 8567.

8. 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 Abstract 8567.

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