Drugs- Novel Drug Regimen Can Improve Stem Cell
Transplantation Outcomes
Novel
Drug Regimen Can Improve Stem Cell Transplantation Outcomes
Dec. 9, 2013 — 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 researchers from Dana-Farber Cancer Institute.
In a new phase 2 trial, patients treated with bortezomib had lower
rates of severe acute GVHD and treatment-related mortality, and experienced
better one-year overall survival than has been seen historically with such patients
receiving standard preventive therapy, the investigators reported at the
American Society of Hematology annual 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 John Koreth, MBBS,
DPhil, of Dana-Farber, the lead author and study PI. 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 it may have a role in
mitigating GVHD, the result of donor immune cells attacking the transplant
recipient’s normal tissues.
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 the first, fourth and seventh day after transplant). 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 percent and 37 percent,
respectively, with one-year treatment-related mortality of 36 percent and 45
percent, respectively, and one-year overall survival of 52 percent and 43
percent, respectively.
In patients treated with bortezomib in the new study, the rate of severe
acute GVHD at 180 days after transplant was only 12 percent. By two years, only
8.8 percent of patients had died from treatment-related mortality, and 5.9
percent had died from disease relapse. Overall survival at two years was high
at 84 percent.
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