Abstract 664

Background:

The prognosis of patients with Hodgkin lymphoma (HL) who relapse following autologous hematopoietic cell transplantation is poor. Although reduced intensity allogeneic hematopoietic cell transplantation (RIC allo-HCT) can induce durable remissions in some patients with relapsed/refractory HL, its use is limited by a lack of disease control prior to transplantation. Brentuximab vedotin (b-vedotin, SGN-35), a novel antibody-drug conjugate, has a 75% objective response rate in patients with relapsed/refractory HL (Chen 2011). To examine the impact of b-vedotin on RIC allo-HCT, we performed a retrospective analysis of relapsed/refractory HL patients who received b-vedotin at City of Hope National Medical Center (COH) and Fred Hutchinson Cancer Research Center (FHCRC)/Seattle Cancer Care Alliance (SCCA) and then went on to receive RIC allo-HCT.

Methods:

Between October 2008 and July 2011, 46 patients with relapsed/refractory HL received b-vedotin at COH and SCCA through Seattle Genetics trials (SGN-35-03, 06, 07, and 08). 16/46 (34.8%) patients subsequently underwent RIC allo-HCT, including 12 at COH (2/12 were transplanted at University of Utah and Wellington Hospital) and 4 at the SCCA. The baseline characteristics are listed in Table 1. All 12 COH patients received fludarabine/melphalan as the conditioning regimen, 5/12 used matched related donors and 7/12 used matched unrelated donors. 10/12 received tacrolimus/sirolimus as graft-versus-host disease (GVHD) prophylaxis and 2 patients received mycophenolate mofetil (MMF) and cyclosporine (CSP). In contrast, 3/4 patients transplanted at the SCCA received haploidentical donors transplantation using fludarabine/cytoxan/2Gy TBI conditioning and cytoxan/tacrolimus/MMF as GVHD prophylaxis while 1/4 underwent conditioning using 2Gy TBI followed by CSP/MMF prophylaxis. Patients were monitored for engraftment, aGVHD, cGVHD, chimerism, and infectious complications per institutional standards. Each institutional review board approved the retrospective analysis of individual center data and we plan to present combined analysis of COH/SCCA data at ASH.

Results:

At COH, the 1 year PFS was 90% (95% CI: 54.0, 98.2) and the 1 year OS was 100% with a median follow-up of 13.2 months (range: 2, 20), In addition, the 1 year relapse rate was 10% (95% CI: 1.7, 46) and the non-relapse mortality at 1 year was 0%. Likewise, all 4 of the SCCA patients are alive and progression-free with a median follow up of 7.2 months (range: 2.9, 19). For the entire cohort the rates of aGVHD and cGVHD were 25% and 63%, respectively. There was no grade III-IV aGVHD and only 1/16 (6.3%) with extensive cGVHD. There was no delay of engraftment or increased incidence of CMV/EBV infections (Table 1). The only patient who relapsed after RIC allo-HCT had progressive disease at the time of transplantation, and 276 days had elapsed between the last dose of b-vedotin to RIC allo-HCT.

Table 1.
COH (n=12)FHCRC/SCCA (n=4)
Median age (range) 32 (23, 55) 28.5 (25, 32) 
Median number of prior regimens (range) 3.4 (2, 6) 5 (2, 6) 
Prior Auto-HCT 11/12 3/4 
Previous XRT 7/12 2/4 
Best response to b-vedotin 5 CR, 7 PR 2 CR, 2 SD 
Median number of cycles of b-vedotin (range) 9.5 (2, 14) 7 (4, 16) 
Intermittent therapy between b-vedotin and allo-HCT 3/12, GVD 2/4, 1 RICE/ASCT, 1 DHAP 
Disease status at end of b-vedotin 4 CR, 4 PR, 4 PD 2 CR, 1 SD, 1 PD (no bulky disease) 
Disease status at transplantation 5 CR, 5 PR, 2 PD (no bulky disease) 2 CR, 1 PR, 1 SD 
Median time from last dose b-vedotin to allo-HCT (range) 41 days (30, 276) 82.5 days (40, 162) 
Type of transplant 5 MRD, 7 MUD 3 haplo, 1 MRD 
Conditioning regimen 12/12 fludarabine/melphalan 3 Flu/Cy/2Gy TBI, 1 2Gy TBI 
GVHD prophylaxis 10/12 Tacro/Siro 2/12 CSP/MTX 3 Cy/TAC/MMF, 1 CSP/MMF 
WBC engraftment (range) 14 days (12, 20) 12 (0, 17) 
Plt engraftment (range) 11 days (9, 16) 8 (0, 14) 
Chimerism 100% 100% 
aGVHD II-IV, III-IV 25%, 0% 25%, 0% 
cGVHD extensive 75%, 8.3% 25%, 0% 
EBV/CMV (PCR reactivation only) EBV 2/12, CMV 2/12 EBV 0/4, CMV 1/4 
COH (n=12)FHCRC/SCCA (n=4)
Median age (range) 32 (23, 55) 28.5 (25, 32) 
Median number of prior regimens (range) 3.4 (2, 6) 5 (2, 6) 
Prior Auto-HCT 11/12 3/4 
Previous XRT 7/12 2/4 
Best response to b-vedotin 5 CR, 7 PR 2 CR, 2 SD 
Median number of cycles of b-vedotin (range) 9.5 (2, 14) 7 (4, 16) 
Intermittent therapy between b-vedotin and allo-HCT 3/12, GVD 2/4, 1 RICE/ASCT, 1 DHAP 
Disease status at end of b-vedotin 4 CR, 4 PR, 4 PD 2 CR, 1 SD, 1 PD (no bulky disease) 
Disease status at transplantation 5 CR, 5 PR, 2 PD (no bulky disease) 2 CR, 1 PR, 1 SD 
Median time from last dose b-vedotin to allo-HCT (range) 41 days (30, 276) 82.5 days (40, 162) 
Type of transplant 5 MRD, 7 MUD 3 haplo, 1 MRD 
Conditioning regimen 12/12 fludarabine/melphalan 3 Flu/Cy/2Gy TBI, 1 2Gy TBI 
GVHD prophylaxis 10/12 Tacro/Siro 2/12 CSP/MTX 3 Cy/TAC/MMF, 1 CSP/MMF 
WBC engraftment (range) 14 days (12, 20) 12 (0, 17) 
Plt engraftment (range) 11 days (9, 16) 8 (0, 14) 
Chimerism 100% 100% 
aGVHD II-IV, III-IV 25%, 0% 25%, 0% 
cGVHD extensive 75%, 8.3% 25%, 0% 
EBV/CMV (PCR reactivation only) EBV 2/12, CMV 2/12 EBV 0/4, CMV 1/4 
Conclusion:

These data suggest that b-vedotin prior to RIC allo-HCT in HL can yield prolonged disease control without a delay in engraftment, increase in non-relapse mortality, aGVHD, cGVHD, and post transplant infectious complications. Such a strategy may allow more patients with relapsed or refractory HL to gain sufficient pre-transplant disease control to undergo this potentially curative procedure.

Disclosures:

Chen:Seattle Genetics: Consultancy, Research Funding. Off Label Use: SGN-35, a novel antibody drug conjugate, is used as salvage therapy for relapsed hodgkin lymphoma prior to allogeneic hematopoietic cell transplantation. Grove:seattle genetics: Employment. Gopal:Bio Marin: Research Funding; SBio: Research Funding; Pfizer: Research Funding; Abbott: Research Funding; Millenium: Honoraria, Speakers Bureau; Cephalon: Research Funding; Piramal: Research Funding; Merck: Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Spectrum: Research Funding; GSK: Research Funding; Biogen-Idec: Research Funding.

Author notes

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Asterisk with author names denotes non-ASH members.