466 Short Course of Post-Transplant Cyclophosphamide and Bortezomib for the Prevention of Graft-Versus-Host-Disease after Matched Related or Unrelated Donor Blood or Marrow Transplant

Track: Poster Abstracts
Saturday, February 14, 2015, 6:45 PM-7:45 PM
Grand Hall CD (Manchester Grand Hyatt)
A. Samer Al-Homsi, MD , College of Human Medicine, Michigan State University, Grand Rapids, MI
Tara S Roy, MS, RNP , Adult Blood and Marrow Transplantation, Spectrum Health, Grand Rapids, MI
Kelli Cole, RN, MSN , Laboratory of Blood and Marrow Transplantation, Spectrum Health, Grand Rapids, MI
Marlee Bogema, RN, BSN , Laboratory of Blood and Marrow Transplantation, Spectrum Health, Grand Rapids, MI
Ulrich Duffner, MD , Pediatric Blood and Bone Marrow Transplantation, Helen DeVos Children's Hospital, Grand Rapids, MI
Stephanie F Williams, MD , College of Human Medicine, Michigan State University, Grand Rapids, MI
Aly A Mageed, MD , Pediatric Blood and Bone Marrow Transplantation, Helen DeVos Children's Hospital, Grand Rapids, MI
Presentation recording not available for download or distribution as requested by the presenting author.
Improved prevention of graft versus host disease (GvHD) without impairing graft versus disease (GvD) effect is paramount to the progress of allogeneic blood and marrow transplantation. Both cyclophosphamide (Cy) and bortezomib (Bor) selectively destroy rapidly proliferating recipient-reactive T cells and may represent a step in the right direction. Post-transplant Cy (PTCy) also induces sustained tolerance by intrathymic depletion of donor T cells while enhancing regulatory T cell expansion. Bor also impairs dendritic cells maturation and function. Herein, we provide updated results to a phase I study combining PTCy & Bor for the prevention of GvHD after sibling or unrelated matched donor peripheral blood stem cell transplantation.

Fifteen patients with median age of 56 (37-66) were enrolled; 5 patients had AML, 4 MDS, 3 CLL, 1 follicular lymphoma, 1 MM, and 1 DLBCL.  Disease risk index was high in 6, intermediate in 4, and low in 5 patients. Patients received reduced-intensity conditioning with fludarabine and busulfan. rATG was also given (range 5-8 mg/kg) to patients receiving graft from unrelated  donor (n=8). Two doses of Bor were given IV, 6 hrs after transplant and 72 hrs thereafter. Three patients were enrolled in each of cohorts 1 and 2 and 9 in cohort 3. The dose of Bor in the 3 cohorts was 0.7, 1, and 1.3 mg/m2 respectively. Cy 50 mg/kg IV was given on days 3 and 4 post-transplant. The median time to neutrophil engraftment was 16 days (13-23). One patient required prolonged foscarnet course and died on day 150 without achieving platelet engraftment. For the remaining 14 patients median time to platelet engraftment was 28 days (15-104). Fourteen patients had full chimerism by day 21. The remaining patient had residual CLL and reached full chimerism by day 118. There was no secondary graft failure. Besides anticipated hematological toxicity, no other grade 3 or 4 occurred. Two patients (13%) died due to treatment on day 150 (RSV pneumonitis) and 200 (acute sepsis).  Two patients enrolled early in the study developed extensive HSV genito-rectal ulcers. No other cases were encountered when the institutional practice changed to start acyclovir on the first day of conditioning instead of day 5. CMV reactivation occurred in 8 patients. One patient developed BK virus-induced hematuria and 1 CNS toxoplasmosis. With median follow-up of 11 months (1-30), the predicted DFS and OS at 2 years were 62% and 66% respectively. The incidence of grade II-IV and III-IV acute GvHD in the 14 evaluable patients was 14% and 7% respectively. Only 1 patient developed visceral GvHD. Three out of 11 patients with follow-up > 6 months developed chronic GvHD (27%).

In sum, PTCy & Bor for GvHD prophylaxis is feasible and permits prompt engraftment. Albeit small, our study suggests low incidence of significant acute GvHD, in particular, visceral. The combination is also attractive by its convenience. The study has been extended to a phase II.

Disclosures:
A. S. Al-Homsi, Millennium Pharmaceuticals, Primary Investigator: Research Funding

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