Immunotherapy may improve HSCT outcomes
VALENCIA, SPAIN—Results of a phase 2 trial suggest a personalized T-cell immunotherapy may improve outcomes in patients undergoing T-cell-depleted haploidentical hematopoietic stem cell transplant (HSCT).
Patients who received the therapy, ATIR101, after HSCT had significant improvements in transplant-related mortality (TRM) and overall survival (OS) when compared to historical controls who received a T-cell-depleted haploidentical HSCT without ATIR101.
None of the patients who received ATIR101 developed grade 3-4 graft-versus-host disease (GVHD), despite the fact that they had not received any prophylactic immunosuppressants. Still, there were a few cases of grade 2 GVHD reported.
Denis-Claude Roy, MD, of the University of Montreal in Québec, Canada, presented the results of this trial at the 42nd Annual Meeting of the European Society of Blood and Marrow Transplantation (abstract O042*). The trial was sponsored by Kiadis Pharma, the company developing ATIR101.
Patients and treatment
The trial included 23 leukemia patients with a median age of 41 (range, 21-64). They were eligible for an allogeneic HSCT but could not find a matching donor in time. Sixteen patients had acute myeloid leukemia, and 7 had acute lymphoblastic leukemia.
All patients were in complete remission (CR) at the time of the HSCT. Fifteen were in CR1, and 8 were in CR2/3. The majority of patients (57%) had a poor prognosis based on their disease risk index and cytogenetic profile.
A myeloablative conditioning regimen was used, which consisted of total body irradiation (1200 cGy; n=11) or melphalan (120 mg/m2; n=12), along with thiotepa (10 mg/kg), fludarabine (30 mg/m2 x 5d), and anti-thymocyte globulin (2.5 mg/kg x 4d).
Patients then received a CD34+ selected graft from a haploidentical donor, containing 11 x 106 CD34+ cells/kg (range, 4.7-24.4) and 0.29 x 104 CD3+ cells/kg (range, 0-1.8).
The patients achieved neutrophil and platelet engraftment at a median of 12 days post-HSCT (range, 8-34 and 9-35, respectively). They did not receive any post-transplant GVHD prophylaxis.
At a median of 28 days post-transplant (range, 28-73), ATIR101 was infused, at a fixed dose of 2 x 106 CD3+ cells/kg.
ATIR101 is a personalized T-cell immunotherapy based on a donor lymphocyte preparation selectively depleted of host-alloreactive T cells through the use of photo-dynamic therapy.
Recipient-reactive T cells from the donor are activated in a unidirectional mixed-lymphocyte reaction. The cells are then treated with a compound known as TH9402, which is selectively retained in activated T cells. Subsequent light exposure eliminates the activated recipient-reactive T cells but preserves the other T cells.
Primary endpoint: TRM
The median follow-up, on March 24, 2016, was 414 days (range, 110-742) post-HSCT. At that point, all patients were beyond 6 months post-HSCT. This allowed for assessment of the primary endpoint, which is TRM at 6 months.
Three cases of TRM were reported, for a rate of 13%. In all cases, the cause of death was an infection.
The researchers compared these results to those in a historic control group. It consisted of 35 patients who matched the inclusion and exclusion criteria of this trial and underwent a similar HSCT procedure from haploidentical family members but without the addition of ATIR101.
TRM was significantly lower (P=0.005) in patients who received ATIR101 after a T-cell-depleted haploidentical transplant than in the historical controls. The 6-month TRM for HSCT + ATIR101 was 13%, compared to 37% for HSCT only.
Relapse and survival
Two patients experienced disease relapse within the first 12 months after HSCT—at days 61 and 90. And 1 patient died from disease relapse within the first 6 months.
The researchers said the low rates of relapse and TRM translated into significantly improved OS for patients undergoing HSCT + ATIR101 compared to the historical controls.
