Post-transplant Regimen Lowers GVHD Rates in Patients With Closely Matched Donors

By Cecilia Brown - Last Updated: December 9, 2022

Patients with closely matched donors who received post-transplant cyclophosphamide, tacrolimus, and mycophenolate mofetil had significantly lower rates of graft-versus-host disease (GVHD) than patients who received tacrolimus plus methotrexate after allogeneic hematopoietic stem cell transplantation (HSCT).

Shernan G. Holtan, MD, of the University of Minnesota, and colleagues presented results from the phase III study from the Blood and Marrow Transplant Clinical Trials Network at the 64th American Society of Hematology Annual Meeting and Exposition.

The study’s investigators randomized adults with hematologic malignancies who were undergoing reduced intensity conditioning allogeneic HSCT to receive post-transplant cyclophosphamide, tacrolimus, and mycophenolate mofetil (n=214) or tacrolimus plus methotrexate (n=217). The patients had 6/6 matched related peripheral blood stem cell donors (n=128), 8/8 matched unrelated donors (n=288), or 7/8 single mismatched donors (n=15).

The study’s primary end point was GVHD/relapse or progression-free survival (GRFS), defined as grade III-IV acute GVHD, chronic GVHD requiring systemic immune suppression, disease relapse/progression, or death from any cause. The secondary end points included the incidence and severity of acute and chronic GVHD, engraftment and chimerism, relapse and progression, infections, and survival.

The group receiving post-transplant cyclophosphamide treatment had a significantly lower hazard of GRFS than the group receiving tacrolimus plus methotrexate (hazard ratio [HR], 0.641; 95% CI, 0.492-0.835; P=.001). The adjusted 1-year GRFS rate was 52.7% in the group of patients receiving the post-transplant cyclophosphamide treatment, whereas it was 34.9% in those receiving tacrolimus plus methotrexate.

“The lower proportion of GRFS events in the [post-transplant cyclophosphamide] arm was due to a reduction in both acute and chronic GVHD,” according to Dr. Holtan and colleagues.

At day 100, the rate of grade III-IV acute GVHD was significantly lower in the patients receiving the post-transplant cyclophosphamide treatment (6.3%) than in patients receiving tacrolimus plus methotrexate (14.7%; P=.001). The 1-year chronic GVHD rate was also significantly lower in patients receiving post-transplant cyclophosphamide (21.9%) than in those receiving tacrolimus plus methotrexate (35.1%; P=.005).

However, patients receiving post-transplant cyclophosphamide had a lower cumulative incidence of engraftment for neutrophils by day 29, platelets by day 100, and lymphocytes by 1 year.

There were similar rates of grade III infections in both treatment groups, but the group receiving post-transplant cyclophosphamide treatment had a significantly higher rate of grade II infections (33.7%) than the group receiving tacrolimus plus methotrexate (23.5%; P=.002). There was no significant difference in cytomegalovirus reactivation rates between groups, nor a significant difference in the proportion of chimerism at day 100 or secondary graft failure.

“[Blood and Marrow Transplant Clinical Trials Network] 1703 met its primary end point, demonstrating a higher 1-year GRFS with [post-transplant cyclophosphamide, tacrolimus, and mycophenolate mofetil] compared to [tacrolimus plus methotrexate] owing to significant improvements in GVHD risk without increased risk of relapse or death,” Dr. Holtan and colleagues concluded. “[Post-transplant cyclophosphamide, tacrolimus, and mycophenolate mofetil], which has become standard of care for mismatched transplants, should also become the standard of care for GVHD prophylaxis from closely matched donors receiving reduced intensity conditioning.”

Holtan SG, Hamadani M, Wu J, et al. Post-transplant cyclophosphamide, tacrolimus, and mycophenolate mofetil as the new standard for graft-versus-host disease (GVHD) prophylaxis in reduced intensity conditioning: results from phase III BMT CTN 1703. Abstract #LBA-4. Presented at the 64th ASH Annual Meeting and Exposition; December 10-13, 2022; New Orleans, Louisiana.

Post Tags:ASH Annual Meeting 2022
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