GVHD Prophylaxis: Similar Outcomes With
PTCy and ATG

Neil Osterweil

March 17, 2021

A newer regimen was no more effective than an older regimen when both were compared for graft versus host disease (GVHD) prophylaxis in patients who underwent reduced-intensity conditioning followed by a hematopoietic stem cell transplant (HSCT) from a 10/10 HLA-matched related or unrelated donor.

These results come from a multicenter randomized trial that compared
post-transplant cyclophosphamide (PTCy) to anti-thymocyte globulin (ATG), which has been used for decades.

There were no significant differences between the two in either disease-free or overall survival, GVHD-free relapse-free survival (GRFS), or nonrelapse mortality, reported lead investigator Eolia Brissot, MD, from the Hôpital Saint-Antoine, Sorbonne University, Paris, France.

Her presentation was judged 'top abstract' at the annual meeting of the European Society for Blood and Bone Marrow Transplantation (EBMT), held virtually because of the pandemic.

ATG has been used for more than 30 years for GVHD prophylaxis in allogeneic HSCT. In contrast, PTCy is the new kid on the block, developed to facilitate haploidentical transplants using unmanipulated bone marrow cells to act as a method for selective allodepletion in vivo.

"PTCy [has proven] to be effective in preventing both acute and chronic GVHD," Brissot commented. "However, controversial outcome data remain when comparing PTCy and ATG according to the type of donors."

Until now, she noted there have been no prospective randomized data  available for patients with donors (related or unrelated) that have 10 of 10 matched human leukocyte antigen (HLA) alleles. Hence, these were the patients studied in this latest trial, and in this population both regimens showed similar outcomes.

A bone marrow transplant specialist who was not involved in the study said that it's a good first step.

"This is an important study to gain preliminary data to design a larger, subsequent phase 3 study," said Zachariah DeFilipp, MD, from the Mass General Cancer Center in Boston, Massachusetts.

"The use of ATG as part of GVHD prophylaxis is common at many centers, especially in Europe, " he explained. "The use of post-transplant cyclophosphamide is being expanded to more settings with transplant, beyond haploidentical transplant.

"Further investigations comparing the use of PTCy to ATG will help determine whether PTCy should be more broadly adopted as a standard-of-care GVHD prophylaxis approach, given currently available regimens," he told Medscape Medical News.

Study Details

The randomized phase 2b study (NCT02876679), conducted in centers in 11 cities in France, compared PTCy with ATG in patients with hematologic malignancies for whom a reduced-intensity allogeneic HSCT was indicated. This included patients age 50 and older, and/or heavily pretreated patients who received an autologous HSCT or more than two prior lines of chemotherapy before allogeneic HSCT, as well as patients with poor performance status due to significant medical comorbidities.

Excluded from the trial were patients with creatinine clearance less than 30 mL/min; bilirubin or liver amino transferases more than three times the upper limit of normal; cardiac ejection fraction less than 40%; or pulmonary impairment with less than 50% lung carbon monoxide diffusing capacity.

Of 90 patients enrolled, 1 experienced a relapse before randomization, and the remaining 89 patients were assigned to either PTCy (experimental arm, 45 patients) or to ATG (control group, 44 patients).

Most patients had good performance status (Eastern Cooperative Oncology Group performance status 0 or 1). Diagnoses included acute myeloid and lymphoblastic leukemia, multiple myeloma, lymphomas, and myelodysplastic syndrome. The median age was 64 years, and the male to female ratio was about 2:1 in both groups.

All patients received "FB2" reduced-intensity conditioning with fludarabine
30 mg/m2 per day for 4 days, and intravenous busulfan 130 mg/m2 per day for 2 days.

Patients in the experimental arm received cyclophosphamide 50 mg/kg/day on days 3 and 4 after transplant. Patients in the control group received ATG 2.5 mg/kg/day on days 3 and 2 prior to transplant.

All patients also received cyclosporine A, and those who had unrelated donors also received mycophenolate mofetil. In all, 39% of patients received cells from matched sibling donors, and 61% received cells from matched unrelated donors.

No Significant Differences Seen

At 12 months of follow-up, there was no significant difference between the trial arms in the primary endpoint of GRFS, a composite of grade 3-4 acute GVHD, chronic GVHD requiring systemic treatment, relapse, or death. The rates of GRFS were 52.2% with PTCy vs. 45% with ATG.

Rates of disease-free survival were 68.5% with PTCy and 67.1% with ATG. The respective 12-month overall survival rates were 78.9% and 80.4%, respectively. The differences were not statistically significant.

The incidence of relapse at 1 year was 22.1% in the ATG group vs. 17.6% in the PTCy group. Respective nonrelapse mortality rates were 10.8% for the ATG group and 14% for the PTCy group. Neither difference was statistically significant.

There were also no significant between-group differences in the incidence at 12-month follow-up of either acute GVHD (34.9% PTCy arm vs. 24.3% ATG arm for grades II-IV combined, and 9.3% PTCy vs. 2.7% ATG for grades III or IV) or chronic GVHD (30.2% ATG vs. 26% PTCy).

The safety analysis showed no significant between-group differences in selected adverse events, including Epstein-Barr viral reactivation, cytomegalovirus reactivation, cardiac adverse events, or hemorrhagic cystitis.

The study was supported by Hospitals of Paris. Brissot and DeFilipp have disclosed no relevant financial relationships.

European Society for Blood and Marrow Transplantation Annual Meeting (EBMT) 2021: Abstract GS-2-2. Presented March 15, 2021.

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