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Recurrent HL after Autotransplant in CR with Brentuximab:

Published byRandolf Quinn Modified over 6 years ago

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Presentation on theme: "Recurrent HL after Autotransplant in CR with Brentuximab:"— Presentation transcript:

1 Recurrent HL after Autotransplant in CR with Brentuximab:
Koen van Besien, MD, PhD Weill Cornell Medical College

2 Recurrent HL after Autotransplant in CR with Brentuximab: ALLO
Koen van Besien, MD, PhD Weill Cornell Medical College

3 Koen van Besien, MD, PhD Weill Cornell Medical College
Recurrent HL after Autotransplant in CR with Brentuximab: But is that the issue? Koen van Besien, MD, PhD Weill Cornell Medical College

4 Frequency of Response to Brentuximab in Refractory Relapsed HL
Zinzani, Hematologica, 98, 1231, 2013

5 Scenario 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

6 Scenario 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

7 Scenario 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

8 Scenario 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

9 Scenario 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

10 Treatment Options for Continue Brentuximab Second Auto Transplant
Allo Transplant

11 Treatment Options for Continue Brentuximab: Second Auto Transplant
Limited Durability Toxicity Second Auto Transplant Allo Transplant

12 Duration of Response to Brentuximab in HL
Duration of CR in alive patients Black Circles: Allogeneic Transplant Gray Circles: Autologous Transplant Zinzani, Hematologica, 98, 1231, 2013

13 Progression-free Survival Comparison All 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

14 Brentuximab Vedotin Significant Adverse Events
Grade 3-4 (from Phase II studies) Peripheral neuropathy % Neutropenia % Fever/neutropenia 0% Thrombocytopenia % Progressive Multifocal Leukencephalopathy? 3 reported cases after 2, 2, and 8 doses of BV BOXED WARNING in BV label Pulmonary Toxicity when given in combination with Bleomycin Contraindication in BV label *Leukemia & Lymphoma 53(11): 2283,2012

15 Treatment Options for Continue Brentuximab: Second Auto Transplant
Limited Durability Toxicity Second Auto Transplant Limited Applicability Allo Transplant

16 Second Autologous TX in HL and NHL relapsing after previous Auto SCT
Alive 4 7 Dead 15 14 Primary disease 10 8  Interstitial pneumonia 1  Infection  Organ failure  New malignancy 2  Other, not specified Smith S, BBMT 2008, 14,

17 Treatment Options for Continue Brentuximab: Second Auto Transplant
Limited Durability Toxicity Second Auto Transplant Allo Transplant

18 Proof of Principle: DLI for Relapsed Disease (n=24)
79% ORR (14 CR, 5 PR) 13 responders (11CR) had no prior salvage 46% had no significant GvHD Relapse incidence 1.00 0.75 0.50 33% 3yr 0.25 0.00 1 2 3 4 5 6 7 8 9 Time post last DLI (years) Nov 06 - Feb 08 Peggs, KS, et al. J Clin Oncol 2011;29:

19 Reduced-intensity Allo-SCT vs. Chemotherapy for Relapse Following ASCT
Overall survival 1.0 0.8 0.6 Surviving RIT group (n=38) 0.4 0.2 Control group (n=34) P=0.0001 Time (days) Thomson KJ, et al. BMT 2008;41:765–770

20 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 12 24 36 48 60 Months Sarina B, et al. Blood 2010;115:3671–7

21 Response-adjusted Transplantation: Restoring Intensity
UCLH – single centre series Salvage (n=61) FDG-PET < Metabolic CR Non-progressive Metabolic CR Progressive Salvage FDG-PET SD or better Progressive Autologous Transplant (BEAM) Allogeneic Transplant (BEAM-C) n=28 n=25 n=8 Thomson KJ, et al. Leukaemia. 2013

22 Transplant Outcomes Autologous Transplant Allogeneic Transplant
Non relapse-related mortality 1 (4%) 2 (8%) Relapse 3 (11%) 5 (21%) Autologous Transplant Allogeneic Transplant OS: 92% OS: 88% PFS: 85% cPFS: 84% PFS: 71% Thomson et al., Leukaemia 2013

23 Reduced Intensity Conditioning Allotransplant following Brentuximab Vedotin for Relapsed cHL
n=18, prior ASCT - 17 Median # of BV cycles - 7 Median time from BV to alloSCT - 62 days (24-276d) Best response to BV - CR 7, PR 8, SD 2, PD1 Type of transplant - 7 MRD, 8 MUD, 3 haplo Acute GVHD % Chronic GVHD 56.3% Median F/U – 12 mo PFS – 92% Chen R et al. Blood 119: 6379: 2012.

24 Treatment Options for Continue Brentuximab: Second Auto Transplant
Limited Durability Toxicity Second Auto Transplant Allo Transplant Highly effective Well tolerated if implemented before multiple treatment failures and with adequate GVHD prophylaxis

25 Scenario 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

26 Scenario 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

27 Scenario 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

28 Scenario 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 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

29 Scenario 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 Gem Ox: PD R5+R6 Brentuximab x 5: PR  PD , Brent + GN x1 Benda x3: PR Donor MRD Haplo Cord 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 ND

30 Conclusions 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

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