1. NCI 9177: Risk-Adapted DA-EPOCH-R in Adults With Burkitt Lymphoma
New Findings in Hematology: Independent Conference Coverage* of ASH 2015, December 5-8, 2015, Orlando, Florida
*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.
DA, dose-adjusted; EPOCH-R, etoposide, prednisolone, vincristine, cyclophosphamide, doxorubicin, rituximab.
This program is supported by educational grants from Amgen, Celgene Corporation, Merck, Incyte, Seattle Genetics, and Takeda Oncology.

2. NCI 9177: Background
Burkitt lymphoma: rare, highly aggressive B-cell non-Hodgkin’s lymphoma with very high tumor proliferation
Treatment strategies modeled after ALL regimens with multiple agents in high- intensity, alternating cycles[1]
Good efficacy but high toxicity in adults, immunosuppressed pts
Risk-adapted therapy used to mitigate toxicity
CHOP: low efficacy in highly proliferating cells (Burkitt, DLBCL)[2,3]
EPOCH-R-based regimens: FFP and OS > 90%[4]
NCI 9177: a multicenter phase II study of risk-adapted DA-EPOCH-R in Burkitt lymphoma[5]
ALL, acute lymphocytic leukemia; CHOP, cyclophosphamide, doxorubicin, vincristine, prednisone; DLBCL, diffuse large B-cell lymphoma; DA, dose-adjusted; EPOCH-R, etoposide, prednisolone, vincristine, cyclophosphamide, doxorubicin, rituximab; FFP, freedom from progression.
1. Mead GM, et al. Ann Oncol. 2002;13: Dave SS, et al. N Engl J Med. 2006;354: Rosenwald A, et al. N Engl J Med. 2002;346: Dunleavy K, et al. N Engl J Med. 2013;369: Dunleavy K, et al. ASH Abstract 342.
Slide credit: clinicaloptions.com

3. NCI 9177: Study Design Multicenter, prospective phase II study
Objective: validation of single center findings
Low-Risk Arm*
DA-EPOCH-RR
2 cycles
(n = 11)
Negative
DA-EPOCH-RR
1 cycle
Routine FU
CT/
FDG-PET
Untreated pts ≥ 18 yrs old with Burkitt lymphoma
(N = 88)
Positive
Repeat CT/
FDG-PET if + after 2 cycles
High-Risk Arm
DA-EPOCH-R
2 cycles
(n = 77)
Negative
Routine FU
DA-EPOCH-R
4 cycles†
CT/
FDG-PET
DA, dose-adjusted; ECOG, Eastern Cooperative Oncology Group; EPOCH-R, etoposide, prednisolone, vincristine, cyclophosphamide, doxorubicin, rituximab; EPOCH-RR, etoposide, prednisolone, vincristine, cyclophosphamide, doxorubicin, dose-dense rituximab; FU, follow up; LDH, lactate dehydrogenase; MTX, methotrexate; PS, performance status.
*Low-risk: stage I or II disease, normal LDH, ECOG PS 0-1, mass size < 7cm; all other pts high risk. †Intrathecal MTX included in high-risk arm on cycles 3, 4, 5.
Slide credit: clinicaloptions.com
Dunleavy K, et al. ASH Abstract 342.

4. NCI 9177: Baseline Characteristics
Baseline characteristics similar to those from other studies in adults, including UK LY06[1]
Characteristic,* %[2]
All
(N = 88)
Low Risk (n = 11)
High Risk
(n = 77)
UK LY06[1]
Low Risk (n = 12)
(n = 40)
Median age, yrs (range)
40 yrs or older
60 yrs of older
46 (18-78) 57 25
38 (19-62) 45 9
47 (18-78) 58 27
26 (15-52)
38 (16-60) 48
Male 82 64 84 83 50
Stage III or IV 73 80
Elevated LDH 56
ECOG PS ≥ 2 18 21 -
Extranodal disease 23
CNS disease 13 15 17
HIV positive 24
CNS, central nervous system; ECOG, Eastern Cooperative Oncology Group; LDH, lactate dehydrogenase; PS, performance status.
*Includes data from 24 sites.
1. Mead GM, et al. Ann Oncol. 2002;13:
2. Dunleavy K, et al. ASH Abstract 342.
Slide credit: clinicaloptions.com

5. NCI 9177: Outcomes by Subgroup
Median follow-up: 25 mos
Subgroup
PFS, %
P Value
OS, %
Overall 84 86
Risk group
Low risk
High risk
100 81
.16
.19
HIV infection status
Positive
Negative 85
.91 88
.77
Age
Younger than 40 yrs
40 yrs or older
.41 83 91
.33
Slide credit: clinicaloptions.com
Dunleavy K, et al. ASH Abstract 342.

6. NCI 9177: Safety
Main on-treatment toxicity observed: infectious deaths in high-risk arm (n = 3)
Cycle 1
Male, 72 yrs of age
Male, 59 yrs of age
Cycle 4
Female, 52 yrs of age
Toxicity profile consistent with previous reports
Regimen administered on an outpatient basis where feasible
Slide credit: clinicaloptions.com

7. NCI 9177: Conclusions
Phase II study suggests DA-EPOCH-R an effective approach for treating Burkitt lymphoma
Treatment-related toxicity markedly reduced compared to standard regimens for Burkitt lymphoma
Excellent outcomes in low-risk pts treated with an abbreviated regimen (3 cycles) without intrathecal therapy
Study accrual is ongoing
Investigators concluded that DA-EPOCH-R is a potential alternative to high-intensity treatment requiring a multicenter setting
DA, dose-adjusted; EPOCH-R, etoposide, prednisolone, vincristine, cyclophosphamide, doxorubicin, rituximab.
Slide credit: clinicaloptions.com
Dunleavy K, et al. ASH Abstract 342.

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