in CR with Brentuximab Koen van Besien MD PhD Weill Cornell Medical College Recurrent HL after Autotransplant in CR with Brentuximab ALLO Koen van Besien MD PhD Weill Cornell Medical College ID: 774797
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Slide1
Recurrent HL after Autotransplant in CR with Brentuximab:
Koen van Besien, MD, PhD
Weill Cornell Medical College
Slide2Recurrent HL after Autotransplant in CR with Brentuximab:ALLO
Koen van Besien, MD, PhD
Weill Cornell Medical College
Slide3Recurrent HL after Autotransplant in CR with Brentuximab:But is that the issue?
Koen van Besien, MD, PhD
Weill Cornell Medical College
Slide4Frequency of Response to Brentuximab in Refractory Relapsed HL
Zinzani
,
Hematologica
, 98, 1231, 2013
Slide5Scenario of HL Failure
MS
Age, PMH
49, CAD, Stents,
MI, HTN, HCHOL
Hist
/Ext
NS. IVB
(Lung, spleen, bone, epidural, BM
R1
ABVD
x6 + IT MTX: PR
PD
R
2
DICE
x3: PR
PD
R3
Brentuximab
x3:
PR
PD
R4
R5+R6
Donor
Cond+GVH
Current Status
Slide6Scenario of HL Failure
MS
SK
Age, PMH
49, CAD, Stents,
MI, HTN, HCHOL
34
Hist
/Ext
NS. IVB
(Lung, spleen, bone, epidural, BM
NS,
IIA
R1
ABVD
x6 + IT MTX: PR
PD
ABVDx4
+XRT
CT
Rel
9 m
R
2
DICE
x3: PR
PD
DICE
x 2 + BUVP Auto: CR
Rel
6 m
R3
Brentuximab
x3:
PR
PD
Brentuximab
x9: CR
R4
R5+R6
Donor
Cond+GVH
Current Status
Slide7Scenario of HL Failure
MS
SK
SG
Age, PMH
49, CAD, Stents,
MI, HTN, HCHOL
34
39
Hist
/Ext
NS. IVB
(Lung, spleen, bone, epidural, BM
NS,
IIA
NS,
II B
R1
ABVD
x6 + IT MTX: PR
PD
ABVDx4
+XRT
CT
Rel
9 m
ABVD x6 PR
PD
R
2
DICE
x3: PR
PD
DICE
x 2 + BUVP Auto: CR
Rel
6 m
DICE x2: SD
R3
Brentuximab
x3:
PR
PD
Brentuximab
x9: CR
GND
CBV Auto (
pul
tox
): CR
Rel
6 m
R4
PEPC: PD
R5+R6
Brentuximab
x 5: PR
PD
Donor
Cond+GVH
Current Status
Slide8Scenario of HL Failure
MS
SK
SG
SC
Age, PMH
49, CAD, Stents,
MI, HTN, HCHOL
34
39
24, ADD, Obesity
Hist
/Ext
NS. IVB
(Lung, spleen, bone, epidural, BM
NS,
IIA
NS,
II B
NS,
IV B (liver)
R1
ABVD
x6 + IT MTX: PR
PD
ABVDx4
+XRT
CT
Rel
9 m
ABVD x6 PR
PD
ABVD x6 PR
PD
R
2
DICE
x3: PR
PD
DICE
x 2 + BUVP Auto: CR
Rel
6 m
DICE x2: SD
ICE
x2:
PD
R3
Brentuximab
x3:
PR
PD
Brentuximab
x9: CR
GND
CBV Auto (
pul
tox
): CR
Rel
6 m
Brentuximab
x2:PD
R4
PEPC: PD
R5+R6
Brentuximab
x 5: PR
PD
Donor
Cond+GVH
Current Status
Slide9Scenario of HL Failure
MS
SK
SG
SC
Age, PMH
34
Hist
/Ext
NS,
IIA
R1
ABVDx4
+XRT
CT
Rel
9 m
R
2
DICE
x 2 + BUVP Auto: CR
Rel
6 m
R3
Brentuximab
x9: CR
R4
R5+R6
Donor
Cond+GVH
Current Status
Slide10Treatment Options for
Continue
Brentuximab
Second Auto Transplant
Allo
Transplant
Slide11Treatment Options for
Continue
Brentuximab
:
Limited Durability
Toxicity
Second Auto Transplant
Allo
Transplant
Slide12Duration of Response to Brentuximab in HL
Duration of CR in alive patients
Black Circles: Allogeneic TransplantGray Circles: Autologous Transplant
Zinzani
,
Hematologica
, 98, 1231, 2013
Slide13Progression-free Survival ComparisonAll Patients versus Patients with CR
12 of 15 patients who remain in long-term follow-up with no evidence of disease had CR; the remaining 3 patients had PR
Presented by S Smith et al, EHA 2012
Slide14Brentuximab VedotinSignificant Adverse Events
Grade 3-4 (from Phase II studies)Peripheral neuropathy 8-10%Neutropenia 20%Fever/neutropenia 0% Thrombocytopenia 8-14%Progressive Multifocal Leukencephalopathy?3 reported cases after 2, 2, and 8 doses of BV BOXED WARNING in BV labelPulmonary Toxicity when given in combination with Bleomycin Contraindication in BV label
*Leukemia & Lymphoma 53(11): 2283,2012
Slide15Treatment Options for
Continue
Brentuximab
:
Limited Durability
Toxicity
Second Auto Transplant
Limited Applicability
Toxicity
Allo
Transplant
Slide16Second Autologous TX in HL and NHL relapsing after previous Auto SCT
NHL
(19)HL (21)Alive47Dead1514Primary disease10 8 Interstitial pneumonia01 Infection01 Organ failure1 1 New malignancy2 1 Other, not specified2 2
Smith S, BBMT 2008, 14, 904-912
Slide17Treatment Options for
Continue
Brentuximab
:
Limited Durability
Toxicity
Second Auto Transplant
Allo
Transplant
Slide18Proof of Principle: DLI for Relapsed Disease (n=24)
Nov 06 - Feb 08
Time post last DLI (years)
0
1
2
3
4
5
6
7
8
0.00
0.25
0.50
0.75
1.00
33% 3yr
9
Relapse incidence
79% ORR (14 CR, 5 PR)
13 responders (11CR) had no prior salvage
46% had no significant
GvHD
Peggs
, KS, et al.
J
Clin
Oncol
2011;29:971-978
Slide19Reduced-intensity
Allo
-SCT vs. Chemotherapy for Relapse Following ASCT
RIT group (n=38)
Control group (n=34)
P=0.0001
Thomson KJ, et al.
BMT 2008;41:765–770
1.0
0.8
0.6
0.4
0.2
0
Surviving
0 1000 2000 3000 4000 5000
Time (days)
Overall survival
Slide20Sarina
B, et al. Blood 2010;115:3671–7
Donor vs. No Donor Analysis in Patients Relapsed Post ASCT
Progression free survival
Overall survival
0.0
0.2
0.4
0.6
0.8
1.0
Donor
No donor
p<0.001
Survival probability
0.0
0.2
0.4
0.6
0.8
1.0
p<0.001
Donor
No donor
0
12
24
36
48
60
Months
0
12
24
36
48
60
Months
Slide21Salvage
Autologous Transplant
(BEAM)
Progressive
Allogeneic Transplant
(BEAM-C)
FDG-PET
Metabolic CR
< Metabolic CR
Non-progressive
Salvage
Progressive
SD or better
(n=61)
Response-adjusted
Transplantation
:
R
estoring
I
ntensity
FDG-PET
n=28
n=25
n=8
UCLH – single centre series
Thomson KJ, et al. Leukaemia.
201
3
Slide22Autologous Transplant
Non relapse-related mortality 1 (4%) 2 (8%)
Relapse 3 (11%) 5 (21%)
Allogeneic Transplant
Transplant Outcomes
OS: 92%
PFS: 85%
PFS: 71%
OS: 88%
cPFS: 84%
Autologous Transplant
Allogeneic Transplant
Thomson
et al
.,
Leukaemia
2013
Slide23Reduced Intensity ConditioningAllotransplant following Brentuximab Vedotin for Relapsed cHL
n=18, prior ASCT - 17Median # of BV cycles - 7Median time from BV to alloSCT - 62 days (24-276d)Best response to BV - CR 7, PR 8, SD 2, PD1Type of transplant - 7 MRD, 8 MUD, 3 haplo
Chen R et al. Blood 119: 6379: 2012.
Acute GVHD 27.8%
Chronic GVHD 56.3%
Median F/U – 12 mo
PFS – 92%
Slide24Treatment Options for
Continue
Brentuximab
:
Limited Durability
Toxicity
Second Auto Transplant
Allo
Transplant
Highly effective
Well tolerated if implemented before multiple
treatment failures and with adequate GVHD prophylaxis
Slide25Scenario of HL Failure
MS
SK
SG
SC
Age, PMH
49, CAD, Stents,
MI, HTN, HCHOL
34
39
24, ADD, Obesity
Hist
/Ext
NS. IVB
(Lung, spleen, bone, epidural, BM
NS,
IIA
NS,
II B
NS,
IV B (liver)
R1
ABVD
x6 + IT MTX: PR
PD
ABVDx4
+XRT
CT
Rel
9 m
ABVD x6 PR
PD
ABVD x6 PR
PD
R
2
DICE
x3: PR
PD
DICE
x 2 + BUVP Auto: CR
Rel
6 m
DICE x2: SD
ICE
x2:
PD
R3
Brentuximab
x3:
PR
PD
Brentuximab
x9: CR
PD
GND
CBV Auto (
pul
tox
): CR
Rel
6 m
Brentuximab
x2:PD
R4
PEPC: PD
R5+R6
Brentuximab
x 5: PR
PD , Brent + GN x1
Donor
Cond+GVH
Current Status
Slide26Scenario of HL Failure
MS
SK
SG
SC
Age, PMH
49, CAD, Stents,
MI, HTN, HCHOL
34
39
24, ADD, Obesity
Hist
/Ext
NS. IVB
(Lung, spleen, bone, epidural, BM
NS,
IIA
NS,
II B
NS,
IV B (liver)
R1
ABVD
x6 + IT MTX: PR
PD
ABVDx4
+XRT
CT
Rel
9 m
ABVD x6 PR
PD
ABVD x6 PR
PD
R
2
DICE
x3: PR
PD
DICE
x 2 + BUVP Auto: CR
Rel
6 m
DICE x2: SD
ICE
x2:
PD
R3
Brentuximab
x3:
PR
PD
Brentuximab
x9: CR
PD
GND
CBV Auto (
pul
tox
): CR
Rel
6 m
Brentuximab
x2:PD
R4
Benda x 2: CR
PEPC: PD
R5+R6
Brentuximab
x 5: PR
PD , Brent + GN x1
Donor
Haplo
Cord
Cond+GVH
Flu Mel ATG
Tacro
MMF
Current Status
6
mo
post
TX
No GVHD
NED
Slide27Scenario of HL Failure
MS
SK
SG
SC
Age, PMH
49, CAD, Stents,
MI, HTN, HCHOL
34
39
24, ADD, Obesity
Hist
/Ext
NS. IVB
(Lung, spleen, bone, epidural, BM
NS,
IIA
NS,
II B
NS,
IV B (liver)
R1
ABVD
x6 + IT MTX: PR
PD
ABVDx4
+XRT
CT
Rel
9 m
ABVD x6 PR
PD
ABVD x6 PR
PD
R
2
DICE
x3: PR
PD
DICE
x 2 + BUVP Auto: CR
Rel
6 m
DICE x2: SD
ICE
x2:
PD
R3
Brentuximab
x3:
PR
PD
Brentuximab
x9: CR
PD
GND
CBV Auto (
pul
tox
): CR
Rel
6 m
Brentuximab
x2:PD
R4
XRT Pelvis
Benda x 2: CR
PEPC: PD
R5+R6
Brentuximab
x 5: PR
PD , Brent + GN x1
Donor
MRD
Haplo
Cord
Cond+GVH
BEAM-CAMPATH-
Tacro
Flu Mel ATG
Tacro
MMF
Current Status
1
yr
post
Tx
-
No GVH NED
6
mo
post
TX
No GVHD
NED
Slide28Scenario of HL Failure
MS
SK
SG
SC
Age, PMH
49, CAD, Stents,
MI, HTN, HCHOL
34
39
24, ADD, Obesity
Hist
/Ext
NS. IVB
(Lung, spleen, bone, epidural, BM
NS,
IIA
NS,
II B
NS,
IV B (liver)
R1
ABVD
x6 + IT MTX: PR
PD
ABVDx4
+XRT
CT
Rel
9 m
ABVD x6 PR
PD
ABVD x6 PR
PD
R
2
DICE
x3: PR
PD
DICE
x 2 + BUVP Auto: CR
Rel
6 m
DICE x2: SD
ICE
x2:
PD
R3
Brentuximab
x3:
PR
PD
Brentuximab
x9: CR
PD
GND
CBV Auto (
pul
tox
): CR
Rel
6 m
Brentuximab
x2:PD
R4
XRT Pelvis
Benda x 2: CR
PEPC: PD
R5+R6
Brentuximab
x 5: PR
PD , Brent + GN x1
Donor
MRD
Haplo
Cord
MRD
Cond+GVH
BEAM-CAMPATH-
Tacro
Flu Mel ATG
Tacro
MMF
Flu Mel
Campath
Tacro
Current Status
1
yr
post
Tx
-
No GVH NED
6
mo
post
TX
No GVHD
NED
18
mo
post
TX
cGHV
skin resolved
NED
Slide29Scenario of HL Failure
MSSKSGSCAge, PMH49, CAD, Stents, MI, HTN, HCHOL3439 24, ADD, ObesityHist/ExtNS. IVB (Lung, spleen, bone, epidural, BMNS, IIANS, II BNS, IV B (liver)R1ABVD x6 + IT MTX: PR PD ABVDx4 +XRTCT Rel 9 mABVD x6 PRPDABVD x6 PRPDR 2DICE x3: PR PDDICE x 2 + BUVP Auto: CR Rel 6 mDICE x2: SDICE x2:PDR3Brentuximab x3: PR PDBrentuximab x9: CR PDGND CBV Auto (pul tox): CR Rel 6 mBrentuximab x2:PDR4XRT PelvisBenda x 2: CRPEPC: PD Gem Ox: PDR5+R6Brentuximab x 5: PR PD , Brent + GN x1Benda x3: PRDonorMRDHaplo CordMRDHaplo CordCond+GVHBEAM-CAMPATH-TacroFlu Mel ATGTacro MMFFlu Mel Campath TacroFlu Mel ATGTacro MMFCurrent Status1 yr post Tx-No GVH NED6 mo post TX No GVHDNED18 mo post TXcGHV skin resolvedNED6 mo post TXNo GVHDND
29
Slide30Conclusions
Responses to
Brentuximab
are rarely durable in HL
Allogeneic transplant is an excellent treatment option and overcomes disease resistance.
With current supportive care and GVHD prophylaxis, the incidence of
cGVHD
is limited.
We
have a donor for all