latest concepts in large cell and hodgkin lymphomas morton coleman, m.d. director, center for...
TRANSCRIPT
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LATEST CONCEPTS IN LARGE CELL AND HODGKIN LYMPHOMAS
LATEST CONCEPTS IN LARGE CELL AND HODGKIN LYMPHOMAS
Morton Coleman, M.D.Director, Center for Lymphoma and Myeloma
New York-Presbyterian Hospital Weill Cornell Medical Center
Clinical Professor of Medicine
Weill Cornell Medical College
Chairman, Medical Affiliates Board
Lymphoma Research Foundation
Morton Coleman, M.D.Director, Center for Lymphoma and Myeloma
New York-Presbyterian Hospital Weill Cornell Medical Center
Clinical Professor of Medicine
Weill Cornell Medical College
Chairman, Medical Affiliates Board
Lymphoma Research Foundation
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Disclosures for Morton Coleman, MD
Employment None
ConsultancyCelgene, Genzyme, GlaxoSmithKline, Millenium, Onyx, Spectrum
Equity Ownership Immunomedics
Research Funding Glaxo Smith Kline, Onyx
Honoraria None
Patents & Royalties None
In compliance with ACCME policy, ASH requires the following disclosures to the session audience:
2012
Clin
ical R
esea
rch
Trai
ning
Inst
itute
Sum
mer
Wor
ksho
p, L
a Jo
lla, C
A
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Disclosures for Morton Coleman, MD, con’t
Speakers Bureau None
Membership on Board of Directors/Advisory Committee Immunomedics, Glaxo Smith Kline
Other None
Presentation includes a description of the following off-label use of a drug or medical device
None
In compliance with ACCME policy, ASH requires the following disclosures to the session audience:
2012
Clin
ical R
esea
rch
Trai
ning
Inst
itute
Sum
mer
Wor
ksho
p, L
a Jo
lla, C
A
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THE THRUST OF CURRENT DEVELOPMENTS
Identify subsets of patients with diffuse large B cell or Hodgkin lymphoma who are either destined to do well or fare poorly using techniques beyond the known clinical predictive factors, particuarly those techniques using molecular changes and/or PET scans.
By applying our better understanding of the (molecular) biology of these diseases, can we not only identify these subsets, but also develop and individualize treatments using less therapy for those with a good prognosis and using novel therapies for those destined to do poorly.
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R-CHOP-21/14 cures about 2/3 of“all comers”: Failure-free survival
R-CHOP14 533 438 355 224 102 25 1
Patients at Risk
R-CHOP21 534 429 358 216 116 25 1
Years from randomisation
R-CHOP21
R-CHOP14
Pro
babi
lity
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
0 1 2 3 4 5 6
0.99 (0.79–1.24)HR (95% CI)
p=0.94Log-rank test
75%75%2-yr FFS
153 (28)155 (29)Events, n (%)
R-CHOP14R-CHOP21
Cunningham et al, ASCO 2011
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N=22831%
Gisselbrecht C, et al. J Clin Oncol 2009; 27(15s): Abstract 8509.
DLBCL patients who recur post R-CHOP-21 do not do well
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Overall survival of patients with DLBCL refractory to
second line therapy is very poor
Elstrom et al , Clin Lymph Myel Leuk, 2010
0 5 10 15 20 250 5 10 15 20 25
0.00
0.
25
0.50
0.
75
1.00
0.00
0.
25
0.50
0.
75
1.00
Pro
po
rtio
n o
f P
atie
nts
Pro
po
rtio
n o
f P
atie
nts
Time (months)Time (months)
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Rosenwald A et al. N Engl J Med. 2002;346:1937-1947
Germinal center vs activated B cell DLBCL
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Lenz G, et al, NEJM November 27, 2008
Outcome by GCB vs non-GCB gene signatures in DLBCL
N=233 patients treated with R-CHOP
PFS OS
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CD10+
-
BCL6
-
GCB
non-GCB+
MUM1+ -
?
?
BCL2
FOXP1
HGAL
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Non-GCB DLBCL is associated with high expression of target genes of
NF-kB transcription factors
Davis, et al, J Exp Med 2001
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Ruan et al, JCO 2010
CHOP-R + bortezomib DLBCL PFS and OS by subtype (n = 40)
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PYRAMID study designDLBCL
diagnosis & subtyping
GCB
Not enrolled
Non-GCB
R
Vc-R-CHOPBortezomib 1.3 mg/m2, d 1, 4
Rituximab 375 mg/m2, d 1Cyclophosphamide 750 mg/m2, d 1
Doxorubicin 50 mg/m2, d 1Vincristine 1.4 mg/m2, d 1
Prednisone 100 mg/d, d 1–5Six treatment cycles q21 days
R-CHOPRituximab 375 mg/m2, d 1
Cyclophosphamide 750 mg/m2, d 1Doxorubicin 50 mg/m2, d 1Vincristine 1.4 mg/m2, d 1
Prednisone 100 mg/d, d 1–5Six treatment cycles q21 days
Follow up every 3 months for 2 yrs
Hans method
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What is a “double hit” lymphoma?
Recurrent breakpoints activating multiple oncogenes, one being MYC
BCL2+/MYC+ most common
BCL6, CCND1 and BCL3 may also occur
Can also have “triple hit”
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Immunophenotype of “double hit” lymphoma
CD10+, GCB phenotype
Lack MUM1, ABC phenotype
BCL2 + also present (with Myc) in a majority of cases
High proliferative index – median 90% Ki67+
Aukema et al, Blood 2011
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Clinical features of “double hit” lymphoma
Aukema et al, Blood 2011
StudyN DH/
total N (%)
DH w prior iNHL
%
Med age
St III/IV %
LDH > Nl
%
BM + %
CNS + %
> 1 ENS %
IPI Hi/HiI
%
Bertrand 2007
10/17 (59%)
10% 58 70% NA NA NA NA 56%
Johnson 2009
54/54 (100%)
46% 62 76% 50% 71% NA 35% 70%
Kanungo 2006
14/14 (100%)
None 55 NA 93% 79% 21% 57% NA
Le Gouill 2007
16/16 (100%)
25% 61 100% 100% 94% 50% 88% 81%
Macpherson 1999
15/39 (38%)
46% 65 92% 80% 69% NA 62% 90%
Niitsu 2009 19/19 (100%)
None 61 100% 100% 84% 21% 63% 89%
Snuderl 2010
20/20 (100%)
15% 64 95% 100% 59% 45% 30% 85%
Tomita 2009 27/27 (100%)
17% 51 96% 93% 65% 9% 65% 87%
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R-CHOP and MYC rearranged DLBCL
Barrans et al, JCO 2010
EFS
OS
35 (14%) with MYC rearrangements
19 also had t(14;18)
3 also had BCL6
7 “triple hit”
Therefore most“MYC+” are “double”or “triple” hit
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DA-R-EPOCH and MYC+ DLBCL
Dunleavy et al, Lugano 2011
EFS
OS
9 MYC+ DLBCL
99 MYC- DLBCL
Similarrisk by IPI
High RR/PFS inBL
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Impact of Induction Regimen and Consolidative Stem Cell Transplantation in Patients with
Double Hit Lymphoma (DHL): A Large Multicenter Retrospective Analysis
Mitul Gandhi, Adam M. Petrich, Ryan Cassaday, Oliver Press, Khushboo A. Shah, Jeremy D. Whyman, Frederick Lansigan, Andrew Zelenetz, Namrata Shah, Timothy Fenske, Francisco J.
Hernandez-Ilizaliturri, Lisa X. Lee, Stefan K. Barta, Shruthi Melinamani, Reem Karmali, Camille Adeimy, Scott Smith, Julie Vose, Neil Dalal, Chadi Nabhan, David Peace, Borko Jovanvoic, Aliyah
Sohani, Andrew Evens, Jorge Castillo, Jeremy S. Abramson
ASH 2013, Abstract 40
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DHL: Impact of R-EPOCH
• Results of chi-square analysis
– Improved CR compared to R-CHOP (p = .005)
– Trend towards improvement w/ other regimens (p = .07)
– Decreased PD compared to R-CHOP (p = .005)
– Decreased PD w/ other intensive regimens (p = .003)
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DHL: Conclusions
• DHL has a poor prognosis, although a subset exists which can achieve durable CR
• R-EPOCH is associated with improved rates of CR and decreased rates of PD
• SCT does not clearly improve OS compared to observation alone in those achieving CR
• Novel approaches and agents are necessary to overcome unfavorable biology
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A Phase III Study of Enzastaurin in Patients with High-risk Diffuse Large B Cell Lymphoma Following
Response to Primary Treatment: The PRELUDE Trial
Michael Crump; Sirpa Leppä; Luis Fayad; Je Jung Lee; Alice Di Rocco; Michinori Ogura; Hans Hagberg; Frederick Schnell; Robert Rifkin; Andreas Mackensen; Fritz Offner; Lauren Pinter-Brown; Sonali Smith; Kensei Tobinai; Su-Peng Yeh; Jun Zhu;
Eric D. Hsi; Marjo Hahka-Kemppinen; Scott P. Myrand; Donald Thornton; Peipei Shi; Tuan Nguyen; Boris Lin; Brad Kahl; Norbert Schmitz; Kerry J. Savage; Thomas
Habermann for PRELUDE Trial Investigators
ASH 2013, Abstract 371
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Background
1Morgillo F, et al. Mol Cancer Ther 2008;7:1698-707; 2Dumstorf CA, et al. Mol Cancer Ther 2010;9:3158-63; 3Robertson MJ, et al. J Clin Oncol 2007;25:1741-6.
R-CHOP = rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone.
The PRELUDE Trial
• Patients with DLBCL and an IPI score of 3-5 at diagnosis who relapse after R-CHOP can have a poor prognosis.
• Enzastaurin is a potent and selective competitive inhibitor of PKCβ.1,2
• Enzastaurin was associated with freedom from progression in a phase II trial in a small subgroup of patients with relapsed or refractory DLBCL, thereby providing the rationale for this study.3
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Background
• PKCβ is the major isoform expressed in normal and malignant B cells.1,2
1Shipp MA, et al. Nat Med 2002;8:68-74; 2Graff JR, et al. Cancer Res 2005;65:7462-9; 3Robertson MJ, et al. J Clin Oncol 2007;25:1741-6.
• PKCβ is required for B cell receptor signaling, activation of NFκB, and VEGF-mediated angiogenesis.3
• Over-expression of PKCβ mRNA and protein is associated with a poor outcome in patients with DLBCL.1
DLBCL = diffuse large B cell lymphoma.
BTK
PI 3K
AKT
mTOR
PLC2
PKCβ
SYK
PP
IKK
NFKB
The PRELUDE Trial
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Disease Free Survival by Treatment Arm for ITT Population
p=0.541
Enzastaurin
Placebo
HR (95% Cl): 0.92 (0.689, 1.216)P = 0.541
Su
rviv
al P
rob
abil
ity
Disease-Free Survival Time (months)Patients at Risk, (n):
504 383 348 259 157 45254 197 165 138 74 18
0 6 12 18 24 30 36 42 48 54 60 66 72 78
Disease-free Survival Time (months)Patients at risk, n:
Enza:Placebo:
100
80
60
40
20
0
The PRELUDE Trial
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Disease-free Survival – GCB vs. Non-GCB by Hans’ Algorithm
GCB vs. non-GCB in the Enzastaurin Arm GCB vs. non-GCB in the Placebo Arm
GCB vs. non-GCB in the Combined Arm
GCB, Enzastaurin (N=79)
Non-GCB, Enzastaurin (N=66)
GCB, Placebo (N=30)
Non-GCB, Placebo (N=40)GCB, Enzastaurin (N=79)
Non-GCB, Enzastaurin (N=66)
GCB, Placebo (N=30)
Non-GCB, Placebo (N=40)
HR (95% Cl): 0.77 (0.42, 1.42)P=0.40
HR (95% Cl): 1.31 (0.56, 3.08)P=0.54
0 6 12 18 24 30 36 42 48 54 60 66 72 78 84 0 6 12 18 24 30 36 42 48 54 60 66 72 78 84
1.0
0.9
0.8
0.7
0.6
0.5
1.0
0.9
0.8
0.7
0.6
0.5
Cox regression determined associations between DFS and GCB/non-GCB status, adjusted for IPI score (3 vs. >3), age (≤60 vs. >60), and prior radiation (yes vs. no).
The PRELUDE Trial
GCB (N=109)
Non-GCB (N=106)
0 6 12 18 24 30 36 42 48 54 60 66 72 78 84
1.0
0.9
0.8
0.7
0.6
0.5
HR (95% Cl): 0.92 (0.56, 1.52)P=0.74
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Discussion and Conclusions
• Enzastaurin did not improve DFS, EFS, or OS vs. placebo in patients with CR after initial treatment for DLBCL and an IPI score of ≥3
• Safety results of PRELUDE were consistent with the established safety profile of enzastaurin when used as a single-agent therapy in lymphoma and other cancers
• Cell-of-origin (GCB vs. non-GCB) was not prognostic for DFS in patients with CR
The PRELUDE Trial
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BENDAMUSTINE (with rituximab, vitamin R)
Three studies reported: Japan, NSH, Germany Doses of B were 120mgm/m2 days 1,2 + R
375 mgm/m2 every three weeks. German study was with unrx’ed elderly (E) Responses ranged from 58% to 69% (E) CR’s ranged from 19% to 54% (E) PFS/OS ranged from 6 to 7.7(E) months Significant toxicity
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Approach to “variant” DLBCLs GCB vs non-GCB
– R-CHOP is standard– Various randomized trials underway
MYC+, DH, TH– Consider FISH/IHC for MYC, BCL2, BCL6– Less favorable with R-CHOP– Unclear if other approaches better– Prospective studies underway, including R-EPOCH
Intensive BL type regimens
R-EPOCH
Less favorable outcome than other DLBCL with R-CHOP– Risk seems to be beyond age, IPI
Less favorable at progression
Rearrangements noted– BCL2 31%– BCL6 18%– C-MYC 13%
C-MYC worse PFS and OS
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In Hodgkin lymphoma, what role do PET Scans play in lessening (toxicity) therapy and enhancing
cure?
May interim PET/CAT scans be of value or should scans be used only at the end of treatment?
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FDG-PET: After one (two treatments) versus two cycles
(four treatments) of therapy
Early determination of treatment sensitivity in Hodgkin lymphoma: FDG-PET/CT after one cycle of therapy has a higher negative predictive value than after two
cycles of therapy
Hutchings, M., Kostakoglu,L., Coleman, M., et al. Submitted for publication
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Participating Nations
Denmark
United States
Italy
Poland
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Patient Population:126 Pts.
Stage I 8% Stage 2 46% Stage 3 19% Stage4 27% B Sxs 56% Bulky 37%
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Comparison of the prognostic value of PET 1 and PET 2: Progression Free
Survival at 2 Years PET 1 PET2
Negative predictive value 98% 91% Positive predictive value 63% 85% Sensitivity 95% 61% Specificity 86% 97% Concordance >90%
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The RAPID Trial in Patients With Clinical Stages IA/IIA Hodgkin
Lymphoma and a “Negative” PET Scan After 3 Cycles ABVD
Radford J, Barrington S, Counsell N, Pettengell R,
Johnson P, Wimperis J, Coltart S, Culligan D, Lister A, Bessell E,
Kruger A, Popova B, Hancock B, Hoskin P, Illidge T, O’Doherty M
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Initial treatment: ABVD x 3
Reassessment: if NR/PD, patient goes off studyif CR/PR, FDG-PET scan performed
4th cycle ABVD then IFRT Randomization
IFRT No further treatment
PET-positive PET-negative
RAPID Trial Design
Radford J, et al. Blood. 2012;120: Abstract 547.
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PET negative;
randomized to
IFRT
(n = 209)
PET negative;
randomized to
NFT
(n = 211)
PET positive;
4th cycle
ABVD/IFRT
(n = 145)
Progressions 9 20 11
Deaths 6 1 8
PFS at 3 years 93.8% 90.7% 85.9%
OS at 3 years 97.0% 99.5% 93.9%
Outcomes After Median Follow-Up of 45.7 Months
Radford J, et al. Blood. 2012;120: Abstract 547.
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Summary 602 pts registered between 2003 and 2010
75% PET-negative at central review after ABVD x 3
In the randomized PET-negative population, 3 yr PFS is 93.8% IFRT and 90.7% NFT
Risk difference -3% is within the maximum allowable difference of -7%
Radford J, et al. Blood. 2012;120: Abstract 547.
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Conclusion
Patients with a negative PET scan after 3 cycles ABVD have an excellent prognosis without further treatment, and for these patients RT can be avoided
Radford J, et al. Blood. 2012;120: Abstract 547.
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Commentary
These data are similar to those reported from Argentina several years ago.
Would the slightly higher rate of false negative PET scans at cycle 3 seen in those patients not receiving adjuvant radiotherapy been avoided had the PET been performed at cycle 2, or better yet, cycle 1
Response-adapted therapy based on quality- controlled/assured PET imaging may become the future standard of care in early-stage HL
Radford J, et al. Blood. 2012;120: Abstract 547.
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An Individual Patient-Data Comparison of German Hodgkin Study Group HD10 and HD11 Combined Modality Therapy
and NCIC Clinical Trials Group HD.6 ABVD Alone
Hay AE, Klimm B, Chen BE, Goergen H, Shepherd LE, Fuchs M,
Gospodarowicz M, Borchmann P, Connors JM, Markova J, Crump M, Lohri A,
Winter JN, Dorken B, Pearcey RG, Volker D, Horning SJ, Eich HT, Engert A,
Meyer RM
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2 ABVD + 20 Gy IFRT
Comparison of NCIC CTG HD.6 and GHSG HD10 and HD11 Staging, Eligibility and
Preferred Arms
4 ABVD + 30 Gy IFRT
4 – 6 ABVD alone
Early, unfavorable
HD11
Early, favorable
HD10
AdvancedHD.6
FavorableUnfavorable
NCIC CTG
GHSG
Advanced
Not necessarily to scale
Hay AE, et al. Blood. 2012;120: Abstract 549.
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Very good prognosis B or Bulk
Early, unfavorable
HD11
Early, favorable
HD10
AdvancedHD.6
FavorableUnfavorable
NCIC CTG
GHSG
Advanced
Not necessarily to scale
Hay AE, et al. Blood. 2012;120: Abstract 549.
Comparison of NCIC CTG HD.6 and GHSG HD10 and HD11 Staging, Eligibility and Preferred ArmsComparison of NCIC CTG HD.6 and GHSG HD10 and HD11 Staging, Eligibility and Preferred Arms
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Outcomes: All Patients
Hay AE, et al. Blood. 2012;120: Abstract 549.
Endpoint
Number
Med. F/U
GHSG HD10/11
406
7.6 Years
NCIG CTG
HD.6
182
11.2 Years
HR
(95% CI)
GHSG
PD/OS
NCIC CTG
PD/OS
8-yr TTP 93% 87% 0.44 (0.24, 0.78) 25/0 23/0
8-yr PFS 89% 86% 0.71 (0.42, 1.18) 25/13 23/4
8-yr OS 95% 95% 1.09 (0.49, 2.40) 19 10
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Overall Summary
Combined modality therapy (CMT) improves disease control by 4%-7%
Superior long-term overall survival with CMT is highly unlikely
The relatively long term outcomes associated with IFRT remain to be clarified
Hay AE, et al. Blood. 2012;120: Abstract 549.
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What’s new for refractory/relalpsing disease?
Evolving Data on Brentuximab Vedotin
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Brentuximab Vedotin Mechanism of Action
Brentuximab vedotin (SGN-35) ADCmonomethyl auristatin E (MMAE), potent antitubulin agent
protease-cleavable linker
anti-CD30 monoclonal antibody
ADC binds to CD30
MMAE disruptsmicrotubule network
ADC-CD30 complex traffics to lysosome
MMAE is released
Apoptosis
G2/M cellcycle arrest
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Long-Term Survival Analyses of an
Ongoing Phase 2 Study of
Brentuximab Vedotin in Patients with
Relapsed or Refractory Hodgkin Lymphoma
R Chen, AK Gopal, SE Smith, SM Ansell, JD Rosenblatt, KJ Savage,
JM Connors, A Engert, EK Larsen, EL Sievers, A Younes
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Overall survival after treatment with Brentuximab
vedotin
• Median observation time from 1st dose: – All patients = 29.5 months
(range, 1.8 to 36.9) – CR patients = 29.1 months
(range, 2.6 to 34.3) • 60/102 patients (59%) remain
alive; median OS has not been reached (95% CI: 28.7, NE)
• Estimated 24-month survival rate* = 65% (95% CI: 55, 74)
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Overall Survival by Cycle 4 PET Status
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Conclusions
After a median observation time of ~2.5 years from first
brentuximab vedotin dose, 60 of 102 patients (59%) remain alive at
last follow up
Median OS has not yet been reached; the estimated 24-mo survival
rate was 65%
– Improved OS strongly correlated with both:
Achievement of CR Negative PET scan at Cycle 4
– Prolonged OS was observed in patients with both long and short progression-free intervals after auto-SCT
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What are we doing new for Advanced-Stage HL
How can we improve the cure rate and reduce the toxicity for advanced stage disease?
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Frontline Therapy With Brentuximab Vedotin Combined with ABVD or
AVD in Patients with Newly Diagnosed Advanced-Stage Hodgkin
Lymphoma
Ansell SM, Connors JM, Park SI, O’Meara M, Younes A
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Study Design Phase I, multicenter, dose-escalation study
Major eligibility criteria
– Treatment-naïve HL patients
– Age ≥18 to ≤60 years
– Stage IIA bulky disease or Stage IIB-IV disease
Treatment design
– 28-day cycles (up to 6 cycles) with dosing on Days 1 and 15
– Dose escalation cohorts – I-6, II-13, III-6, IV-6, expansion-20
A(B)VD
Brentuximab Vedotin
Cycle 1 Cycle 2 Cycle 3
6 Cycles +/- XRT
Weeks0 2 4 6 8 10 12
Ansell SM, et al. Blood. 2012;120: Abstract 798.
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Response Results at End of Front-Line Therapy
Response per Investigatora
ABVD with brentuximab
vedotin
N = 22
AVD with brentuximab
vedotin
N = 25
Response at end of front-line therapy,
n (%)
Complete remission 21 (95) 24 (96)
Progressive disease 0 1 (4)
Not evaluable due to AEs 1b (5) 0
• Response results at end of front-line therapy:
◦ ABVD cohorts: 21 of 22 CR (95%)
◦ AVD cohorts: 24 of 25 CR (96%)• In addition, 1 patient withdrew consent and 3
patients were lost to follow-up prior to completion of front-line therapy and were not evaluable for response
Ansell SM, et al. Blood. 2012;120: Abstract 798.
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Carde et al. J Clin Oncol 30, 2012 (suppl; abs 8002)
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Study Design HL Stages III-IV IPS ≥ 3
Randomized Phase III Trial
Carde et al. J Clin Oncol 30, 2012 (suppl; abs 8002)
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Progression-Free Survival(Not a predefined study endpoint)
Carde et al. J Clin Oncol 30, 2012 (suppl; abs 8002)
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Treatment Discontinuations for Toxicity
ABVD
n = 272
BEACOPP
n = 269
Toxicity 10 28
Respiratory related (not including
infections)
7 5
Hematological 4
Infection / meningitis / septicemia 10
Septic / toxic shock 1 4
Hepatic 2 2
Cardiac 1
Neurological 1
Allergy to etoposide 1Carde et al. J Clin Oncol 30, 2012 (suppl; abs 8002)
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Event-Free Survival
Carde et al. J Clin Oncol 30, 2012 (suppl; abs 8002)
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Overall Survival
Carde et al. J Clin Oncol 30, 2012 (suppl; abs 8002)
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CONCLUSIONS
EFS (primary endpoint) is similar between treatment arms.
However, more progressions / relapses were observed with ABVD
while early discontinuations were more frequent with BEACOPP
In this high-risk group, conventional dose escalation with
BEACOPP 4+4 provides a better PFS compared to ABVD, yet not
good enough to improve OS
Additional considerations (treatment burden & cost, fertility issues,
risk of relapse, risk of salvage, immediate & late morbidities) may
guide physician / patient decisions toward ABVD or BEACOPP,
which currently may share the claim for “current standard of care”
Carde et al. J Clin Oncol 30, 2012 (suppl; abs 8002)
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CONCLUSIONS A GENERAL SURVEY OF STUDIES COMPARING BEACOPP TO
ABVD ALMOST ALL CONSISTENTLY SHOW A SUPERIOR
PROGRESSION FREE SURVIVAL FOR BEACOPP BUT LONG
TERM SURVIVAL SEEMS TO BE COMPARABLE DUE TO THE
TOXICITY OF BEACOPP.
AS WITH LIMITED STAGE DISEASE, CAN INTERIM PET SCANS
BE USED TO SELECT OUT THOSE PATIENTS NOTNEEDING
MORE AGGRESSIVE THERAPY AND THEREBY AVOID ALL THE
UNNECESSARY TOXICITY OF BEACOPP? IS GENETIC
INSTABILITY ADVANCED BY DR DIEHL TRULY OPERATIVE
EVEN AS EARLY AS (A PET SCAN AFTER) ONE CYCLE
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3 cycles of ABVD without IFRT has an excellent outcome for favorable stage IA/IIA
patients who are at the conclusion of treatment are PET neg.
Disease control may be slightly better for CMT as compared with CT (3%-7%),
although a survival difference is unlikely although long-term effects of IF (reduced)
RT are unknown.
BV + AVD results are comparable, if not superior, to ABVD for patients with stage
III/IV HL. Phase III comparison has opened. BV has been shown effective in
relapsing/refractory patients including those failing transplant. It is being
incorporated into many strategies for the rx of ‘difficult’ HL pts.
The overall results with ABVD are at least equal to BEACOPP with less toxicity.
Interim PET scans may prove valuable in the rx strategies for HL.
SUMMARY
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Acknowledgment
Clinical Research Jia Ruan, M.D., Ph.D.Richard Furman, M.D.John P. Leonard, M.D.Peter Martin, M.D.Maureen Joyce, R.N.Patricia Glenn, R.N.Jamie KetasJessica HansenKaren WeilJennifer O’LoughlinRebecca Elstrom, M.D. (Gen.)Lale Kostakoglu, M.D. (Sinai)Stanley Goldsmith, M.D.
Biostatistician
Ken Chueng, Ph.D. (Columbia)
Madhu Mazumdar, Ph.D. (Cornell)
Translational Core Maureen Lane, Ph.D. (Cornell)Maureen Ward
Laboratory Research Ari Milneck, M.D., Ph.D.(Cornell)Katherine Hajjar, M.D. (Cornell)Shahin Rafii, M.D. (Cornell)
Lymphoma Research Foundation
ASCO Foundation (YIA, CDA)
NIH / NHLBI
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THANK YOU FOR
YOUR ATTENTION