OPTIMAL>60: Radiotherapy by PET Status After R-CHOP or R-CHLIP in Elderly Pts With DLBCL 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 DLBCL, diffuse large B-cell lymphoma; R-CHLIP, rituximab plus doxorubicin/liposomal vincristine/cyclophosphamide; R-CHOP, rituximab plus doxorubicin/vincristine/cyclophosphamide. This activity is supported by educational grants from AbbVie, Amgen, AstraZeneca, Celgene Corporation, Genentech, Halozyme, Incyte, and Merck & Co., Inc.

RT for PET-Negative Bulky Disease After ImmunoCT in Elderly DLBCL Pts: Background RICOVER-60: inferior EFS, PFS, and OS in elderly pts with DLBCL/bulky disease receiving R-CHOP without vs with RT[1] UNFOLDER: early closure of no RT arm in phase III study of young pts with DLBCL/bulky disease receiving R-CHOP due to inferior EFS without vs with RT[2] Current analysis includes interim data from OPTIMAL>60 evaluating whether RT can be spared in elderly pts with PET- negative DLBCL following R-CHOP or R-CHLIP[3] CT, chemotherapy; DLBCL, diffuse large B-cell lymphoma; EFS, event-free survival; R-CHLIP, rituximab plus doxorubicin/liposomal vincristine/cyclophosphamide; R-CHOP, rituximab plus doxorubicin/vincristine/cyclophosphamide; RT, radiotherapy. 1. Held G, et al. J Clin Oncol. 2014;32:1112-1118. 2. ClinicalTrials.gov. NCT00278408. 3. Pfreundschuh M, et al. ASCO 2017. Abstract 7506. Slide credit: clinicaloptions.com

OPTIMAL>60: Study Design Randomized (factorial assignment), open-label phase III study Planned interim analysis occurred at 40% of expected events, compared results with RICOVER-60 pts receiving 6xCHOP-14 + 8xR + RT to bulky (>7.5 cm) sites 6xCHOP-14* + Rituximab Pts 61-80 yrs of age with CD20+ DLBCL, IPI 2-4, and IPI 1 bulk (N = 187) 6xCHOP-14* + Opti-Rituximab† 39.6 Gy RT only for pts with PET-positive bulk 6xCHLIP-14‡ + Rituximab 6xCHLIP-14‡ + Opti-Rituximab† CHLIP, doxorubicin/liposomal vincristine/cyclophosphamide; CHOP, doxorubicin/vincristine/cyclophosphamide; DLBCL, diffuse large B-cell lymphoma; IPI, International Prognostic Index; R, rituximab; RT, radiotherapy. *Conventional vincristine 2 mg. †Given on an optimized dosing schedule. ‡Liposomal vincristine 2 mg/m2. Slide credit: clinicaloptions.com Pfreundschuh M, et al. ASCO 2017. Abstract 7506.

OPTIMAL>60: Baseline Demographics Characteristic OPTIMAL>60 (n = 187) RICOVER-60* (n = 117) P Value Pts with bulky disease, % 49 50 .985 Male, n (%) 111 (59) 62 (53) .275 Median age, yrs (range) > 70 yrs of age > 75 yrs of age 70 (61-79) 92 (49) 32 (17) 68 (61-80) 39 (33) 17 (15) .021 .007 .551 LDH > UNV, n (%) 144 (77) 76 (65) .022 ECOG PS > 1, n (%) 18 (10) 27 (23) .001 Stage III/IV, n (%) 128 (68) 69 (59) .092 Extranodal involvement > 1, n (%) 77 (41) 24 (21) < .001 IPI, n (%) 1 2 3 4, 5 43 (23) 62 (33) 64 (34) 20 (17) 36 (31) 34 (29) .041 B symptoms, n (%) 60 (33) 54 (46) .020 BM involvement, n (%) 12 (6) 5 (4) .429 BM, bone marrow; CHOP, doxorubicin/vincristine/cyclophosphamide; ECOG, Eastern Cooperative Oncology Group; IPI, International Prognostic Index; LDH, lactate dehydrogenase; PS, performance status; R, rituximab. *Pts receiving 6xCHOP-14 + 8xR. Slide credit: clinicaloptions.com Pfreundschuh M, et al. ASCO 2017. Abstract 7506.

OPTIMAL>60 vs RICOVER-60: Radiotherapy PET positive: 48% (80/166) Received RT: 33% (62/187) RICOVER-60 Received RT: 57% (67/117) Relative reduction with PET- based approach: 42% Reason for No RT, %- OPTIMAL>60 RICOVER-60 PD 44 36 Medical reasons, toxicity 50 33 Protocol violation -- 20 Negative biopsy 6 Other 11 PD, progressive disease; RT, radiotherapy. Slide credit: clinicaloptions.com Pfreundschuh M, et al. ASCO 2017. Abstract 7506.

OPTIMAL>60 vs RICOVER-60: PFS PFS in Pts Receiving 6xCHOP-14 + 8xR Multivariate Analysis of PFS by Factor HR (95% CI) P Value OPTIMAL>60 vs RICOVER-60 0.7 (0.3-1.4) .261 LDH > UNV 2.1 (1.2-3.7) .009 ECOG PS > 1 1.7 (1.0-2.8) .046 Stage III/IV 1.3 (0.8-2.1) .323 Extranodal involvement > 1 1.3 (0.8-2.0) .298 > 75 yrs of age 1.4 (0.9-2.3) .180 Male 1.6 (1.0-2.4) .039 1.0 OPTIMAL>60 (n = 47) RICOVER-60 (n = 117) 0.9 79% 0.8 P = .602 0.7 75% 0.6 0.5 Proportion 0.4 0.3 0.2 CHOP, doxorubicin/vincristine/cyclophosphamide; ECOG, Eastern Cooperative Oncology Group; LDH, lactate dehydrogenase; PS, performance status; R, rituximab. 0.1 10 20 30 40 50 60 70 80 90 100 110 120 Mos Median time of observation: 24 mos. Slide credit: clinicaloptions.com Pfreundschuh M, et al. ASCO 2017. Abstract 7506. Reproduced with permission.

OPTIMAL>60 vs RICOVER-60: OS OS in Pts Receiving 6xCHOP-14 + 8xR Multivariate Analysis of OS by Factor HR (95% CI) P Value OPTIMAL>60 vs RICOVER-60 0.5 (0.2-1.2) .121 LDH > UNV 2.5 (1.3-5.0) .007 ECOG PS > 1 1.9 (1.0-3.3) .035 Stage III/IV 1.2 (0.7-2.1) .607 Extranodal involvement > 1 1.3 (0.8-2.2) .312 > 75 yrs of age 1.4 (0.8-2.5) .240 Male 1.9 (1.1-3.1) .014 1.0 88% OPTIMAL>60 (n = 47) RICOVER-60 (n = 117) 0.9 0.8 P = .307 0.7 78% 0.6 0.5 Proportion 0.4 0.3 0.2 CHOP, doxorubicin/vincristine/cyclophosphamide; ECOG, Eastern Cooperative Oncology Group; LDH, lactate dehydrogenase; PS, performance status; R, rituximab. 0.1 10 20 30 40 50 60 70 80 90 100 110 120 Mos Median time of observation: 24 mos. Slide credit: clinicaloptions.com Pfreundschuh M, et al. ASCO 2017. Abstract 7506. Reproduced with permission.

OPTIMAL>60: Outcome by PET Status, RT PFS OS 1.0 1.0 0.9 0.9 0.8 0.8 0.7 0.7 0.6 0.6 0.5 0.5 Proportion Proportion 0.4 0.4 0.3 0.3 PET negative (n = 86) PET positive/RT (n = 62) PET positive/no RT (n = 18) PET negative (n = 86) PET positive/RT (n = 62) PET positive/no RT (n = 18) 0.2 0.2 RT, radiotherapy. 0.1 0.1 10 20 30 40 50 60 10 20 30 40 50 60 Mos Mos Slide credit: clinicaloptions.com Pfreundschuh M, et al. ASCO 2017. Abstract 7506. Reproduced with permission.

OPTIMAL>60: Conclusions At interim analysis in elderly pts with DLBCL, PET-based RT strategy for bulky disease safe, reduced proportion of pts receiving RT by 42% vs previous RICOVER-60 study approach Pts with PET-negative bulky disease after R-CHOP or R-CHLIP can be spared RT without detriment to treatment outcomes Study investigators suggest that addition of RT to PET-positive bulky disease following CT may compensate for worse prognosis in this subgroup CT, chemotherapy; DLBCL, diffuse large B-cell lymphoma; R-CHLIP, rituximab plus doxorubicin/liposomal vincristine/cyclophosphamide; R-CHOP, rituximab plus doxorubicin/vincristine/cyclophosphamide; RT, radiotherapy. Slide credit: clinicaloptions.com Pfreundschuh M, et al. ASCO 2017. Abstract 7506.

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