Analysis of Pre-Transplant Therapy with Brentuximab Vedotin for Relapsed/Refractory Hodgkin Lymphoma on Outcomes of Reduced Intensity Conditioned Allogeneic Hematopoietic Cell Transplantation
Authors: Wirk Baldeep , Storer Barry E. , Maloney David G , Gopal Ajay K , Cassaday Ryan D , Salit Rachel , O'Donnell Paul V. , Sandmaier Brenda M. , Flowers Mary E.D. 
Published: October 2019

Abstract
Background: The impact of prior salvage therapy with brentuximab vedotin (BV) for relapsed/ refractory Hodgkin lymphoma (HL) on long-term outcomes after reduced intensity conditioned (RIC) allogeneic hematopoietic cell transplantation (allo-HCT) is unknown. Early studies (Chen et al Biol Blood Marrow Transplant 2014; 20: 1864-1868) suggested an improved 2-year progression free survival (PFS) with BV salvage given before allo-HCT compared to patients without prior BV treatment. In the current study, we analyzed the impact of prior therapy on the incidence of chronic graft-versus-host disease (cGVHD) and other major outcomes in patients, who received an RIC allo-HCT for relapsed HL.
Methods: This is a retrospective study of relapsed/refractory HL patients who had RIC allo-HCT between 2005-2014 at the Fred Hutchison Cancer Research Center. Patients were grouped according to prior history of salvage therapy with or without BV pre allo-HCT. Baseline patient characteristics are shown in the Table.
Results: Of the 62 consecutive allo-HCT recipients in this study, 25 had prior therapy with BV (BV group) and 37 received other chemotherapy alone (No BV group) for relapsed HL before allo-HCT. More patients in the BV group were in complete remission at allo-HCT (Table). The 100 day acute GVHD and 5 year cGVHD incidence for the BV vs. no BV group were 58% (95% confidence intervals [CI]: 39%-78%) vs. 65% (95% CI: 50%-80%), p=0.6 and 46% (95% CI: 26%-67%) vs. 51% (95% CI: 35%-68%), p=0.66, respectively. The 5 year non-relapse mortality and relapse/ progression for the BV vs. no BV group were 8% (95% CI: 1%-19%) vs. 25% (95% CI: 11%-38%), p=0.13 and 46% (95% CI: 24%-67%) vs. 38% (95% CI: 22%-53%), p0.98. The 5 year PFS and overall survival for BV vs. no BV group were 46% (95% CI: 25%-68%) vs. 38% (95% CI: 22%-53%), p=0.44 and 78% (95% CI: 60%-95%) vs. 56% (95% CI: 40%-72%), p=0.14. The major cause of death in both groups was relapsed HL.
Conclusion: With longer follow-up, similar incidences of cGVHD, PFS and OS were observed in patients who received salvage therapy for relapsed/refractory HL prior to allo-HCT with or without BV. Any potential differences in cGVHD and other major outcomes need to be tested in a larger population.
Table 1. Characteristics Prior treatment with Brentuximab vedotin Yes N=25 No N=37 Median age, years (range) 27 (14-47) 32 (17-64) Disease stage at diagnosis, n (%) I II III IV 2 (8)11 (44)7 (28)5 (20) 0 (0)15 (41)12 (32)10 (27) Prior history of local radiation pre allo-HCT 20 (80) 29 (78) No. of prior lines of therapies pre allo-HCT 4 (2 - 10) 3 (2 - 7 ) Prior autologous HCT, n (%) 0 1 2 (tandem auto) 1 (4) 21 (84) 3 (12) 0 (0) 35 (96) 2 (4) Disease status at allo-HCT, n (%) Complete remission Partial remission Progressive disease 9 (36) 13 (52) 3 (12) 7 (19)20 (54)10 (27) Median interval from diagnosis to allo-HCT, months (range) 33 (10.7-222) 30.7 (5-292) Graft type, n (%) Bone Marrow Peripheral blood stem cells 9 (36) 16 (64) 15 (41) 22 (59) Donor type, n (%) Haploidentical Matched related Matched unrelated Mismatch unrelated 16 (64) 5 (20) 4 (16) 0 (0) 17 (46) 14 (38) 5 (14) 1 (2) Conditioning for allo-HCT, n (%) FLU/CY/TBI (2 Gy) FLU/TBI (2 Gy) FLU/TBI (3 Gy) TBI (2 Gy) 16 (64) 6 (24) 1 (4) 2 (8) 17 (46) 15 (40) 0 (0) 5 (14) GVHD prophylaxis, n (%) CNI/MMF/post transplant CY CNI+MMF+/- other 16 (64) 9 (36) 17 (46)20 (54) Median follow-up, months (range) 34 (4 - 99) 84 (34 - 121) Abbrev: FLU fludarabine, CY cyclophosphamide, TBI total body irradiation,CNI calcineurin inhibitor, MMF mycophenolate mofetil

Disclosures
Maloney: Seattle Genetics: Honoraria; Roche/Genentech: Honoraria; Janssen Scientific Affairs: Honoraria; Juno Therapeutics: Research Funding. Gopal:Gilead, Spectrum, Pfizer, Janssen, Seattle Genetics: Consultancy; Spectrum, Pfizer, BioMarin, Cephalon/Teva, Emergent/Abbott. Gilead, Janssen., Merck, Milennium, Piramal, Seattle Genetics, Giogen Idec, BMS: Research Funding; Millennium, Seattle Genetics, Sanofi-Aventis: Honoraria. Cassaday:Seattle Genetics: Research Funding; Pfizer: Research Funding. Sandmaier:Gilliad: Honoraria; ArevaMed: Honoraria; Jazz Pharmaceutical: Honoraria; Seattle Genetics: Honoraria; Abmit: Research Funding; Bellicum: Research Funding.