The combination of post-transplant cyclophosphamide and tacrolimus (PTCy-TK) outperformed conventional graft-versus-host disease (GVHD) prophylaxis in patients undergoing allogeneic hematopoietic cell transplantation (alloHCT), according to a poster presented at the 2021 ASH Annual Meeting by Maria Queralt Salas, MD, from the Hospital Clinic of Barcelona in Spain.
“The continuous refinement of transplant techniques has led to a reduction of transplant-related toxicity resulting in an increasing number of alloHCT performed in older patients,” the authors explained. “Since 2014, [PTCy-TK] has been progressively implemented as GvHD prophylaxis for related, matched, and mismatched unrelated donor transplantation.” In this report, Dr. Salas and colleagues shared observations from the use of PTCy-TK at their institution.
Between January 2014 and June 2020, 147 adults with hematologic malignancies and who were at least 50 years old underwent alloHCT either from matched related or unrelated donor. Seventy-two (48.9%) patients received PTCy 50 mg/kg/day intravenously on day 3 and 4 after alloHCT, followed by tacrolimus, initiated at a dose of 0.03/kg/24-hour on day 5 after alloHCT. Therapy was titrated to achieve a therapeutic level of 5-15 mg/mL. Other GVHD prophylaxis strategies included calcineurin inhibitors combined with methotrexate, mycophenolate mofetil, or sirolimus.
Overall survival (OS) and GVGD-free/relapse-free survival (GRFS) were considered the main outcome variables. To analyze the independent impact of PTCy-TK prophylaxis on OS and GRFS, a multivariate Cox regression analysis was performed including GVHD prophylaxis, Disease Risk Index, and transplant year as explanatory variables, together with other variables with prognostic value in the univariate analysis.
The authors reported that the baseline characteristics were similar between each GVHD prophylaxis group. Most patients underwent alloHCT with peripheral blood (97%). Of note, 53 out of 72 patients receiving PTCy-TK were transplanted between July 2017 and December 2020, and more than 90% of patients receiving PTCy-TK had unrelated donors as their source.
For patients receiving PTCy-TK, the median of days to neutrophil (20 vs. 16; p < 0.01) and platelet (19 vs. 11; p < 0.01) engraftment were higher than for those receiving standard prophylaxis. However, the differences between the incidences of viral reactivations and infections were not statistically significant between the two groups, the researchers reported.
At 100 days post-alloHCT, the cumulative incidence of grade II-IV acute GVHD was 21.9% in the PTCy-TK group versus 21.5% in the standard GVHD prophylaxis group (p = 0.88). Grade III-IV acute GVHD at day 100 was 9.2% versus 9.3% (p = 0.88). Although the rates of aGVHD were comparable, the use of PTCY-TK resulted in a significant reduction on the incidence of moderate or severe chronic GVHD at one year (9% vs. 31.5%; p < 0.01).
One-year rates of OS, non-relapse mortality, and relapse were all similar between GVHD prophylaxis regimens:
- OS: 72.1% with PTCy-TK vs. 66.7% for conventional prophylaxis (hazard ratio [HR] = 0.98; p = 0.91)
- NRM: 18.1% vs. 13.3% (HR = 1.20; p = 0.63)
- relapse rates: 18.1% vs. 22.9% (HR = 0.86; p = 0.65)
“The use of this innovative combination provides superior GRFS than the use of conventional GVHD prophylaxis in older adults undergoing alloHCT, with comparable transplant-related mortality and relapse rates,” the authors concluded. “GRFS is a composite endpoint considered a surrogate outcome of health-related quality of life, and the improvement of this parameter is remarkable in PTCy-TK alloHCT, especially for older patients.” The findings are “encouraging,” particularly when considering that older patients with hematologic disorders have a higher risk of developing transplant-related toxicity, the researchers added.