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Compared with anti-thymocyte globulin, post-transplant cyclophosphamide appears to more successfully prevent graft-versus-host disease in patients with acute lymphoblastic leukemia, resulting in a lower incidence of relapse and improved survival.
Post-transplant cyclophosphamide (PTCy) as a prophylactic treatment against graft-versus-host disease (GvHD) appeared to yield a decreased incidence of relapse while improving leukemia-free survival (LFS) and overall survival (OS) compared with anti-thymocyte globulin (ATG) in adult patients with acute lymphoblastic leukemia (ALL) undergoing unmanipulated haploidentical hematopoietic cell transplantation (HCT), according to results from a retrospective multicenter analysis published in Haematologica.
The 2-year LFS rate was 24.1% (95% CI, 14.5%-33.8%) among patients in the ATG group and 39.6% (95% CI, 33.6%-45.5%) for patients in the PTCy group (P = .007). Additionally, patients in the PTCy group, relative to those in the ATG group, had a lower risk of therapy failure (HR, 0.67; 95% CI, 0.46-0.97; P = .03), which is the inverse of LFS.
“GvHD prevention strategies such as ATG, and more recently PTCy, accompanying unmanipulated haploidentical allografts have reinvigorated and ushered in a new era of haploidentical HCT for hematologic malignancies,” the investigators wrote. “While ATG is directed against a wide range of epitopes, thus allowing extensive T-cell depletion, PTCy selectively targets alloreactive T cells rapidly proliferating early after an HLA-mismatched transplant, without affecting the non-dividing hematopoietic progenitor cells.”
A total of 434 adult patients with ALL who underwent haploidentical HCT were identified for this retrospective study utilizing the European Society for Blood and Marrow Transplantation registry. Patients were divided according to the GvHD prophylaxis they received, with 98 patients being assigned to the ATG group and 336 patients in the PTCy group. Median follow-up was approximately 2 years.
The study’s primary end point was LFS, with key secondary end points including acute GvHD, chronic GvHD, relapse incidence, non-relapse mortality, GvHD-free/relapse-free survival (GRFS), and OS. Eligible patients needed to be 18 years or older with ALL and have undergone haploidentical HCT between 2007 and 2017.
The 100-day cumulative incidence of grade 2 to 4 acute GvHD was 32.7% (95% CI, 23.4%-42.3%) in the ATG group compared with 30.5% (95% CI, 25.5%-35.6%) in the PTCy group (P = .37). For the incidence of grade 3/4 acute GvHD, the corresponding rates were 11.6% (95% CI, 6.1%-18.9%) and 14.1% (95% CI, 10.6%-18.2%) for patients in the ATG and PTCy groups, respectively (P = .56).
Non-relapse mortality at 2 years was similar among both groups of patients, with rates of 32.9% (95% CI, 23.1%-43.1%) and 26.7% (95% CI, 21.8%-31.8%) in the ATG and PTCy groups, respectively (P = .23). Moreover, the cumulative incidence of disease relapse at 2 years among patients with ALL in the ATG group was 43% (95% CI, 32%-53.5%) compared with 33.8% (95% CI, 28.1%-39.5%) for patients in the PTCy group (P = .11).
Two-year OS rates were 27.4% (95% CI, 17.4%-37.3%) for patients in the ATG group compared with 48.4% (95% CI, 42.3%- 54.6%) for patients in the PTCy group (P = .001). Research also suggested that PTCy prophylaxis was associated with improved survival when compared with ATG prophylaxis (HR, 0.60; 95% CI, 0.42-0.82; P = .003). Rates of GRFS at 2 years were 20% (95% CI, 10.9%-29.1%) and 31.8% (95% CI, 26.2%-37.5%) in the ATG and PTCy groups, respectively (P = .04).
A total of 225 patients died at the last follow-up, including 66 patient deaths in the ATG group and 159 deaths in the PTCy group. The most common causes of death in the ATG and PTCy groups, respectively, were ALL relapse (36.5% vs 38.1%), GvHD (19.1% vs 14.2%), and infections (31.8% vs 30.3%).
“In the absence of prospective, randomized data, our results suggest that PTCy as GvHD pro- phylaxis may be considered over ATG in patients with ALL undergoing haploidentical HCT. Our data warrant confirmation in prospective randomized studies,” the investigators concluded.
Nagler A, Kanate AS, Labopin M, et al. Post-transplant cyclophosphamide versus anti-thymocyte globulin for graft-versus-host disease prevention in haploidentical transplantation for adult acute lymphoblastic leukemia. Haematologica. 2021;106(6):1591-1598. doi:10.3324/haematol.2020.247296