Posttransplant Cyclophosphamide/Abatacept Reduces Moderate, Severe GVHD Compared With SOC

The prophylactic regimen combining posttransplant cyclophosphamide and abatacept (Orencia; PTCy+Aba) demonstrated a reduction in graft-versus-host disease (GVHD) compared with the traditional standard of care (SOC) of tacrolimus and methotrexate, according to results from a prospective phase 2 trial (NCT03680092). The findings, published in Blood Advances, suggest a potential new avenue for improving outcomes in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). The Kaplan-Meier estimates of moderate and severe chronic GVHD were 0% in patients treated with PTCy+Aba vs 65.8% in patients treated with SOC (P <.0001).¹

Further, GVHD-free, relapse-free survival (GRFS) was 62.5% in patients who received PTCy+Aba vs 24.1% in patients who received SOC (P =.010).

The open-label, single center trial compared PTCy+Aba for 6 months vs methotrexate and SOC in patients receiving a peripheral blood allogeneic allogeneic hematopoietic stem cell transplantation (HSCT) from a matched donor for a high-risk hematologic malignancy with either myeloablative (MA) or reduced-intensity conditioning (RIC).

The primary end point was moderate/severe chronic GVHD at 1 year after transplant. Secondary end points were: GRFS and chronic GVHD and relapse-free survival (CRFS) at 1 year, overall chronic GVHD (including mild), grade 2 to 4 and 3 to 4 acute GVHD rate, overall survival (OS) and disease-free survival at 1 year, and transplant-related mortality.

What Was the Study Design?

Investigators planned to enroll 50 patients randomly assigned to the treatment and control arms. Patients were undergoing their first allogeneic transplantation with the use of peripheral blood grafts from an 8/8 matched unrelated donor or matched related donor (matched at HLA-A, HLA-B, HLA-C, and HLA-DRB1 at high resolution on DNA-based typing).

A total of 43 patients were enrolled but 3 patients did not receive treatment after enrollment: 2 patients were randomly assigned to the SOC arm and their insurance did not allow participation, and the third patient withdrew consent before randomization.

What Were the Patient Demographics?

The mean age of patients in the treatment arm was 48 years (mean 15.5) and 47 years (mean 16.5) in the control arm. There were 14 males in the treatment arm and 11 in the control arm. The most common disease in the treatment arm (n = 9) and the control arm (n = 7) was acute myeloid leukemia and acute lymphoid leukemia (n = 7, n = 5, respectively). No patients had multiple myeloma.

Mid-Trial Protocol Change

Initially, patients were randomly assigned to receive the SOC and the experimental arms and stratified by donor type (matched related donor vs matched unrelated donor) and by conditioning (MA vs RIC).

However, in December 2021, the FDA approved Aba for GVHD prophylaxis.² As a result the investigators changed the SOC to include abatacept in combination with methotrexate and tacrolimus. The investigators amended the protocol and stopped enrolling on the SOC arm. All subsequent patients were treated on the PTCy+Aba arm.

What Were the Secondary End Points?

Investigators reported that the secondary end point of GRFS was 62.% in the treatment arm vs 24.1% in the control arm and was statistically significant (P = .010). CRFS was 66.7% in the PTCy+Aba arm vs 28.6% in the SOC arm (P = .022).

At 1 year there were 2 deaths on the PTCy+Aba arm, both due to relapse; and 3 on the SOC arm (1 due to relapse). There were no treatment-related deaths on the PTCy+Aba arm. On the SOC arm, 1 patient died of idiopathic pneumonia syndrome and 1 patient died of infectious complications (toxoplasmosis) who had also had secondary graft failure. There was no statistically significant difference in the rates of OS at 1 year (PTCy+Aba, 92%;SOC, 80%; P = .28).

There was no statistically significant difference in the disease-free survival at 1 year (PTCy+Aba, 68.0%; SOC, 92.9%; P = .105).

Grade 3/4 acute GVHD rate was 4.2% on the PTCy+Aba arm (n = 1) and 21.4% (n = 3) on the SOC arm (P = .092), whereas grade 2 to 4 acute GVHD occurred in 12.5% on PTCy+Aba and 35.7% on SOC (P = .068).

Regarding safety, infection was the most common adverse event (AE) for both arms. One patient in the SOC arm died from infection and 1 patient on the SOC arm developed posttransplant lymphoproliferative disorder. AEs reported in the SOC arm but not the treatment arm were thrombotic microangiopathy, nephrotoxicity, hyptertension, and neurotoxicity. Investigators noted that these are commonly associated with tacrolimus.

Investigators attributed the reduction in chronic GVHD to the strikingly low number of chronic GVHD cases seen in the PTCy+Aba experimental arm. Koura D et al wrote that, "These findings make it an important addition to the growing body of literature of PTCy+Aba GVHD prophylaxis studies because there remains a significant need for well-tolerated GVHD prophylaxis regimens that effectively prevent chronic GVHD.”

REFERENCES:

1. Koura D, Dykes K, Goodman A, et al. A prospective clinical trial of GVHD prophylaxis with posttransplant cyclophosphamide and abatacept. Blood Adv. 2025;9(16):4336-4344. doi:10.1182/bloodadvances.2024015094

2. FDA approves abatacept for prophylaxis of acute graft versus host disease. News release. Accessed September 16, 2025. https://tinyurl.com/3n2pb4zy