In the recently completed BMT CTN 1703 clinical trial, MCW cancer researchers joined institutions from across the nation to test the current standard of care for preventing graft-versus-host disease (GVHD) against an experimental regimen consisting of three drugs: cyclophosphamide, tacrolimus, and mycophenolate mofetil. Their results, which were published in New England Journal of Medicine in June, demonstrated that the new regimen was more effective at preventing GVHD and came with fewer side effects than the current gold standard.
“The current standard of care to prevent GVHD after allogeneic hematopoietic stem cell transplantation (HSCT) is a combination of a calcineurin inhibitor, such as tacrolimus or cyclosporine, and methotrexate. However, these options are either marginally efficacious or can increase the risk of relapse and/or infections,” said study co-investigator Mehdi Hamadani, MD, Professor, Hematology and Medical Oncology.
“This landmark trial may change the standard of care for patients who have blood and marrow transplants. Our results provide strong evidence that the post-transplantation cyclophosphamide (PTCy) approach is superior for minimizing the risk of GVHD and for preventing disease relapse,” he added.
The phase 3 trial enrolled 431 adults who had undergone blood and marrow transplantation (BMT) for leukemia or lymphoma; participants were randomly assigned to either the experimental or standard treatment arm. The study results showed that one year after transplantation, 52.7% of patients receiving the cyclophosphamide platform (experimental prophylaxis) were alive, free from GVHD, and without cancer relapse or progression, compared to 34.9% of patients receiving methotrexate and tacrolimus (standard prophylaxis).
Researchers in the BMT community have worked for decades to reduce the risk and severity of GVHD. The new PTCy-based approach provides patients with a promising treatment that can selectively target and eliminate alloreactive T cells—which are responsible for causing GVHD—while sparing the non-alloreactive T cells.
The multicenter study was supported by the national Blood and Marrow Transplant Clinical Trials Network Data Coordinating Center, which is located at MCW. Cancer Center investigators led integral phases of the trial, including conception, design, development, activation, conduct, accrual, final analysis, and dissemination. Researchers are now conducting studies to investigate the PTCy treatment strategy in cases of mismatched transplantation. Dr. Hamadani said positive results could help to expand transplant options for patients in underserved populations.
“Our Blood and Marrow Transplant and Cellular Therapy Program is a national leader in transplant-related care and research, advancing therapies and other targeted approaches to save more lives. Several ongoing studies within the program are looking at ways to further reduce the risk of GVHD by employing novel strategies such as cytokine inhibition, modulation of JAK/STAT pathway, and CSF1R signaling,” he said.
Read the full study in New England Journal of Medicine.