1. 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.

2. 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: ClinicalTrials.gov. NCT
3. Pfreundschuh M, et al. ASCO Abstract 7506.
Slide credit: clinicaloptions.com

3. 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 xR + RT to bulky (>7.5 cm) sites
6xCHOP-14* + Rituximab
Pts 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 Abstract 7506.

4. 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 xR.
Slide credit: clinicaloptions.com
Pfreundschuh M, et al. ASCO Abstract 7506.

5. 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 Abstract 7506.

6. OPTIMAL>60 vs RICOVER-60: PFS
PFS in Pts Receiving 6xCHOP xR
Multivariate Analysis of PFS by Factor
HR (95% CI)
P Value
OPTIMAL>60 vs RICOVER-60
0.7 ( )
.261
LDH > UNV
2.1 ( )
.009
ECOG PS > 1
1.7 ( )
.046
Stage III/IV
1.3 ( )
.323
Extranodal involvement > 1
1.3 ( )
.298
> 75 yrs of age
1.4 ( )
.180
Male
1.6 ( )
.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 Abstract Reproduced with permission.

7. OPTIMAL>60 vs RICOVER-60: OS
OS in Pts Receiving 6xCHOP xR
Multivariate Analysis of OS by Factor
HR (95% CI)
P Value
OPTIMAL>60 vs RICOVER-60
0.5 ( )
.121
LDH > UNV
2.5 ( )
.007
ECOG PS > 1
1.9 ( )
.035
Stage III/IV
1.2 ( )
.607
Extranodal involvement > 1
1.3 ( )
.312
> 75 yrs of age
1.4 ( )
.240
Male
1.9 ( )
.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 Abstract Reproduced with permission.

8. 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 Abstract Reproduced with permission.

9. 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 Abstract 7506.

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