Adding bortezomib (Velcade) to standard preventive therapy for graft-versus-host-disease (GVHD) results in improved outcomes for patients receiving stem cell transplants from mismatched and unrelated donors, according to research presented at the 2013 American Society of Hematology (ASH) Annual Meeting, December 7-10, 2013, in New Orleans, Louisiana.
In a new phase 2 trial, patients treated with bortezomib had lower rates of severe acute GVHD and treatment-related mortality, and experienced better 1-year overall survival than has been seen historically with such patients receiving standard preventive therapy, the investigators reported at the meeting.
“This regimen appears to improve not just GVHD prevention but, more importantly, overall and relapse-free survival for myeloablative transplant recipients lacking matched sibling donors,” said lead author and study principal investigator John Koreth, MBBS, DPhil, of the Dana-Farber Cancer Institute in Boston, Massachusetts. The senior author is Edwin P. Alyea, III, MD, also of Dana-Farber.
Stem cell transplantation following myeloablation (high-dose chemotherapy to wipe out the patient’s bone marrow and immune system) is a curative therapy in advanced or aggressive hematologic malignancies, Koreth said. However, recipients who lack preferred matched sibling donors have worse outcomes, with higher treatment-related mortality and severe GVHD, and poorer survival.
Bortezomib, a proteasome inhibitor drug, is a mainstay of treatment for multiple myeloma. In addition to killing cancer cells, bortezomib dampens some immune responses, suggesting that it may have a role in mitigating GVHD.
The prospective, single-arm, phase 2 trial of a bortezomib-based regimen enrolled 34 patients with hematologic malignancies who received myeloablative stem cell transplants. In addition to standard GVHD prophylaxis medications—tacrolimus and methotrexate—the patients received three doses of bortezomib (on days 1, 4, and 7 posttransplant). The treatment was well tolerated with no patients missing doses because of toxicity.
Historically, recipients of unrelated and mismatched donor transplants have severe acute GVHD rates of 28% and 37%, respectively, with a 1-year treatment-related mortality of 36% and 45%, respectively, and a 1-year overall survival of 52% and 43%, respectively.
In patients treated with bortezomib in the new study, the rate of severe acute GVHD at 180 days posttransplant was only 12%. By 2 years, only 8.8% of patients had died from treatment-related mortality, and 5.9% had died from disease relapse. Overall survival at 2 years was high at 84%.
Koreth said that a randomized trial of bortezomib for GVHD prevention is ongoing at Dana-Farber.