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4406 Analysis of Pre-Transplant Therapy with Brentuximab Vedotin for Relapsed/Refractory Hodgkin Lymphoma on Outcomes of Reduced Intensity Conditioned Allogeneic Hematopoietic Cell Transplantation

Clinical Allogeneic Transplantation: Results
Program: Oral and Poster Abstracts
Session: 732. Clinical Allogeneic Transplantation: Results: Poster III
Monday, December 7, 2015, 6:00 PM-8:00 PM
Hall A, Level 2 (Orange County Convention Center)

Baldeep Wirk, MD1, Barry E. Storer, PhD1,2*, David G Maloney, MD, PhD1,3, Ajay K Gopal, MD3, Ryan D Cassaday, MD4, Rachel Salit, MD1,3*, Paul V. O'Donnell, MD, PhD1, Brenda M. Sandmaier, MD3,5 and Mary E.D. Flowers, MD1,3

1Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA
2University of Washington, Seattle, WA
3Division of Medical Oncology, University of Washington, Seattle, WA
4Division of Hematology, University of Washington, Seattle, WA
5Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA

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.

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 .

*signifies non-member of ASH