BRIGHT: 5-Yr Follow-up of First-line BR vs R-CHOP/R-CVP in Pts With iNHL or MCL CCO Independent Conference Highlights* of the 2017 ASCO Annual Meeting; June 2-6, 2017; Chicago, Illinois *Clinical Care Options (CCO) is an independent medical education organization that provides conference coverage and other unique educational programs for healthcare professionals BR, bendamustine/rituximab; iNHL, indolent non-Hodgkin lymphoma; MCL, mantle cell lymphoma; R-CHOP, rituximab plus cyclophosphamide/doxorubicin/vincristine/prednisone; R-CVP, rituximab plus cyclophosphamide/vincristine/prednisone. This activity is supported by educational grants from AbbVie, Amgen, AstraZeneca, Celgene Corporation, Genentech, Halozyme, Incyte, and Merck & Co., Inc.

First-line BR vs R-CHOP/R-CVP in iNHL or MCL: Background BRIGHT: randomized, open-label phase III noninferiority study of BR vs R-CHOP or R-CVP in treatment-naive pts with iNHL or MCL BR noninferior to R-CHOP/R-CVP for CR (primary endpoint; 31% vs 25%; P = .0225)[1] ORR for BR vs R-CHOP/R-CVP: 97% vs 91% (P = .0102)[1] Incidence of vomiting, nausea, drug hypersensitivity increased with BR; peripheral neuropathy/paresthesia, alopecia, constipation increased with R- CHOP/R-CVP (all P < .05)[1] Improved QoL with BR vs R-CHOP/R-CVP[2] Current analysis reports results from 5-yr follow-up study[3] BR, bendamustine/rituximab; iNHL, indolent non-Hodgkin lymphoma; MCL, mantle cell lymphoma; QoL, quality of life; R-CHOP, rituximab plus cyclophosphamide/doxorubicin/vincristine/prednisone; R-CVP, rituximab plus cyclophosphamide/vincristine/prednisone. 1. Flinn IW, et al. Blood. 2014;123:2944-2952. 2. Burke JM, et al. Clin Lymphoma Myeloma Leuk. 2016;16:182-190.e1. 3. Flinn I, et al. ASCO 2017. Abstract 7500. Slide credit: clinicaloptions.com

BRIGHT 5-Yr Follow-up: Study Design Preassignment by investigator Bendamustine 90 mg/m2 IV Days 1-2 + Rituximab 375 mg/m2 IV Day 1 (28-day cycles) Bendamustine or R-CHOP R-CHOP standard dosing (21-day cycles) Treatment-naive pts with iNHL or MCL (N = 447) 5-yr follow-up Bendamustine 90 mg/m2 IV Days 1-2 + Rituximab 375 mg/m2 IV Day 1 (28-day cycles) Bendamustine or R-CVP R-CVP standard dosing (21-day cycles) BR, bendamustine/rituximab; DoR, duration of response; EFS, event-free survival; iNHL, indolent non-Hodgkin lymphoma; MCL, mantle cell lymphoma; R-CHOP, rituximab plus cyclophosphamide/doxorubicin/vincristine/prednisone; R-CVP, rituximab plus cyclophosphamide/vincristine/prednisone. All regimens, including BR, given for 6 cycles with option to increase to 8 cycles at investigator discretion. R-CHOP: R 375 mg/m2 IV Day 1; C 750 mg/m2 IV Day 1; D 50 mg/m2 IV Day 1; V 1.4 mg/m2 IV Day 1; P 100 mg PO Days 1-5. R-CVP: R 375 mg/m2 IV Day 1; C 750 or 1000 mg/m2 IV Day 1; V 1.4 mg/m2 IV Day 1; P 100 mg PO Days 1-5. Investigator-assessed time-to-event endpoints: PFS, EFS, DoR, OS Stratified by preassigned treatment, lymphoma type Slide credit: clinicaloptions.com Flinn I, et al. ASCO 2017. Abstract 7500. Standard dosing in slidenotes.

BRIGHT 5-Yr Follow-up: Pt Disposition R-CHOP/R-CVP Randomized (ITT),* n 224 223 Treated (safety population), n 221 215 Evaluable (primary endpoint), n 213 206 Completed ≥ 6 cycles of treatment, n 203 196 Received rituximab maintenance, % 43 45 Second-line treatment, % Bendamustine regimen† Other 22 3 8 11 34 12 4 17 BR, bendamustine/rituximab; ITT, intent to treat; R-CHOP, rituximab plus cyclophosphamide/doxorubicin/vincristine/prednisone; R-CVP, rituximab plus cyclophosphamide/vincristine/prednisone. *Population included in time-to-event analyses. †Mostly BR. Slide credit: clinicaloptions.com Flinn I, et al. ASCO 2017. Abstract 7500.

BRIGHT 5-Yr Follow-up: PFS 1.0 0.9 0.8 0.7 0.6 0.5 PFS 0.4 0.3 5-Yr Rate, % (95% CI): 65.5 (58.5-71.6) vs 55.8 (48.4-62.5) HR: 0.61 (95% CI: 0.45-0.85; P = .0025) 0.2 BR R-CHOP/R-CVP 0.1 BR, bendamustine/rituximab; MCL, mantle cell lymphoma; R-CHOP, rituximab plus cyclophosphamide/doxorubicin/vincristine/prednisone; R-CVP, rituximab plus cyclophosphamide/vincristine/prednisone. 2 4 6 8 10 12 18 24 30 36 42 48 54 60 66 72 Mos Pts at Risk, n BR R-CHOP/R-CVP 224 223 218 205 210 201 202 194 197 191 194 183 191 179 183 162 177 147 160 134 154 126 146 114 139 105 131 100 122 94 37 11 0 0 BR associated with significantly increased PFS in overall pt population (P = .0025) and in subgroup analyses in pts with MCL and when BR compared with R-CVP (both P < .05); similar trends seen in pts with iNHL and when BR compared with R-CHOP Slide credit: clinicaloptions.com Flinn I, et al. ASCO 2017. Abstract 7500. Reproduced with permission.

BRIGHT 5-Yr Follow-up: PFS by Lymphoma Type iNHL MCL 1.0 1.0 0.9 0.9 0.8 0.8 0.7 0.7 0.6 0.6 0.5 0.5 BR R-CHOP/R-CVP BR R-CHOP/R-CVP PFS PFS 0.4 0.4 0.3 0.3 0.2 0.2 5-Yr Rate, %: 70.3 vs 62.0 HR: 0.70 (95% CI: 0.49-1.01; P = .0582) 5-Yr Rate, %: 39.7 vs 14.2 HR: 0.40 (95% CI: 0.21-0.75; P = .0035) BR, bendamustine/rituximab; iNHL, indolent non-Hodgkin lymphoma; MCL, mantle cell lymphoma; R-CHOP, rituximab plus cyclophosphamide/doxorubicin/vincristine/prednisone; R-CVP, rituximab plus cyclophosphamide/vincristine/prednisone. 0.1 0.1 2 4 6 8 10 12 18 24 30 36 42 48 54 60 66 72 2 4 6 8 10 12 18 24 30 36 42 48 54 60 66 72 Mos Mos Slide credit: clinicaloptions.com Flinn I, et al. ASCO 2017. Abstract 7500. Reproduced with permission.

BRIGHT 5-Yr Follow-up: DoR Population* 5-Yr DoR, % (95% CI) HR (95% CI) P Value BR R-CHOP/R-CVP All pts 65.5 (58.3-71.7) 56.9 (49.3-63.9) 0.66 (0.47-0.92) .0134 Pts with iNHL 70.5 (62.8-76.9) 62.4 (54.3-69.5) 0.73 (0.50-1.07) .1051 Pts with MCL 39.7 (22.8-56.1) 15.9 (4.1-34.5) 0.47 (0.24-0.91) .0231 *Pts at risk, n (BR vs R-CHOP/R-CVP): all: 209 vs 194; iNHL: 173 vs 167; MCL: 36 vs 27. BR associated with significantly increased DoR in overall pt population and pts with MCL in subgroup analysis (P < .05) BR, bendamustine/rituximab; DoR, duration of response; iNHL, indolent non-Hodgkin lymphoma; MCL, mantle cell lymphoma; R-CHOP, rituximab plus cyclophosphamide/doxorubicin/vincristine/prednisone; R-CVP, rituximab plus cyclophosphamide/vincristine/prednisone. Slide credit: clinicaloptions.com Flinn I, et al. ASCO 2017. Abstract 7500.

BRIGHT 5-Yr Follow-up: OS, EFS Population 5-Yr OS, % (95% CI) HR (95% CI) P Value BR (n = 224) R-CHOP/R-CVP (n = 223) All pts 81.6 (75.7-86.3) 85.0 (79.2-89.2) 1.15 (0.72-1.84) .5461 Treatment allocation had no significant effect on OS in overall pt population or pt subgroups BR associated with significantly increased EFS in overall pt population and pts with MCL in subgroup analysis (P < .05) BR had higher rate of secondary malignancy vs R-CHOP/R-CVP (19% vs 11%; P = .022); however, with NHL and nonmelanoma skin cancer excluded, difference becomes nonsignificant (10% vs 6%; P = .133) BR, bendamustine/rituximab; EFS, event-free survival; MCL, mantle cell lymphoma; NHL, non-Hodgkin lymphoma; R-CHOP, rituximab plus cyclophosphamide/doxorubicin/vincristine/prednisone; R-CVP, rituximab plus cyclophosphamide/vincristine/prednisone. Slide credit: clinicaloptions.com Flinn I, et al. ASCO 2017. Abstract 7500.

Conclusions In treatment-naive pts with iNHL or MCL, first-line BR: Significantly increased 5-yr PFS, DoR, and EFS vs R-CHOP/R-CVP in overall pt population and MCL subgroup PFS benefit greater in BR vs R-CVP comparison Associated with increased risk of secondary malignancy vs R-CHOP/R-CVP Treatment allocation had no significant effect on 5-yr OS BR, bendamustine/rituximab; DoR, duration of response; EFS, event-free survival; iNHL, indolent non-Hodgkin lymphoma; MCL, mantle cell lymphoma; R-CHOP, rituximab plus cyclophosphamide/doxorubicin/vincristine/prednisone; R-CVP, rituximab plus cyclophosphamide/vincristine/prednisone. Slide credit: clinicaloptions.com Flinn I, et al. ASCO 2017. Abstract 7500. Slide credit: clinicaloptions.com

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