Background: Graft versus host disease (GVHD) is one the major causes of mortality and morbidity after an allogeneic stem cell transplantation. We hypothesized that we can induce post-transplant tolerance by using the combination of post-transplant cyclophosphamide (PTCy) and abatacept (CTLA4Ig) for GVHD prophylaxis. PTCy when given on Days +3 and +4 can eliminate host-reactive donor T cells. CTLA4Ig blocks the costimulatory signals given through CD28 to naïve donor T cells thus favoring an anergic phenotype that promotes tolerance towards recipient derived antigens. CTLA4Ig gives an activating signal to NK cells and therefore has the ability to preserve the graft-versus-tumor effect.

Methods: We have initiated a 50 patient randomized clinical trial. Patients with hematologic malignancies in need of a transplant and with an 8/8 matched donor are randomized 1:1 to tacrolimus and methotrexate for GVHD prophylaxis (standard of care arm) or PTCy on days +3 and +4 followed by CTLA4Ig on days +5, +14,+28, +56, +84, +112, +140 and +168. Patients are stratified by conditioning regimen (myeloablative vs reduced intensity) and by donor type (matched sibling vs matched unrelated donor). The primary endpoint is chronic GVHD at 1 year as a marker of tolerance induction. Secondary endpoints include acute GVHD rate, relapse rate, overall survival, GVHD-relapse-free-survival, transplant related mortality and infection rate. Post-transplantation immune reconstitution studies include measuring T cell and NK cell phenotype, PD-1 expression, and alloreactivity to recipient and third party at predetermined time points.

Results: 25 patients have been treated on this study, 10 of which are on the experimental arm. Patients on the experimental arm have been followed for up to 516 days post-transplant. So far no cases of chronic GVHD or grade 3-4 acute GVHD have been observed in the experimental arm. All the patients have engrafted and there have been no treatment related deaths.

Conclusions: The combination of PTCy and CTLA4Ig for GVHD prophylaxis is feasible. This ongoing study will examine its ability to induce post-transplant tolerance.


Tzachanis:Kite, a Gilead Company: Consultancy, Research Funding, Speakers Bureau; Partner: Consultancy; Fate Therapeutics: Research Funding; Genentech: Research Funding; Bristol Myers Squibb: Research Funding; Incyte: Research Funding; EUSA: Consultancy; Takeda: Consultancy, Speakers Bureau; Magenta: Consultancy; Kyowa Kirin: Consultancy. Goodman:Seattle Genetics: Consultancy, Speakers Bureau; EUSA Pharma: Consultancy, Honoraria. Mangan:Elevate Bio: Other: ad board.

OffLabel Disclosure:

abatacept: using as part of graft versus host disease prophylaxis

Sign in via your Institution