Rx Improved Stem Cell Transplant Success and Survival

Velcade lowered GVHD and improved survival of stem cell transplant patients

(RxWiki News) To avoid potentially lethal complications, stem cell transplants had to use cells donated by relatives of the patient or perfectly matched donors. Not anymore. Researchers are expanding the possibilities.

Velcade (bortezomib) added to other preventive medications lowered the incidence of acute graft-versus-host-disease (GVHD) and impoved one-year overall survival in patients who received stem cell transplants from mismatched and unrelated donors.

This regimen may expand curative treatment options for patients with advanced or aggressive blood cancers.

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A team of investigators led by John Koreth, MBBS, DPhil, of Dana-Farber Cancer Institute in Boston, are conducting the ongoing phase 2 trial involving patients with various types of hematologic (blood) cancers.

Stem cell transplants are designed to replace diseased blood cells with healthy cells that come either from the patient or from a donor.

In the past, donated cells have had to come from a sibling or perfectly matched donor to improve survival and help prevent the patient’s immune system from attacking the donor cells — a transplant complication called graft-versus-host disease (GVHD).

Today, donor cells don't have to be perfectly matched (mismatched) and can come from individuals unrelated to the patient.

Before the transplant takes place, high-dose chemotherapy is used to shut down the patient’s immune system and wipe out the bone marrow where new blood cells are created. This process is called myeloablation.

This trial enrolled 34 patients who had myeloablative stem cell transplants using mismatched or unrelated donor cells. Velcade was added to other medications used to help prevent GVHD — tacrolimus (brand names, Astagraf, Hecoria, Prograf, Protopic) and methotrexate (Trexall, Folex PFS).

Velcade is used to treat the blood cancer, multiple myeloma, and is also known to tamp down the immune system.

Trial participants received three doses of Velcade, on the first, fourth, and seventh day after the transplant.

Patient outcomes were better than what’s typical for transplants that use mismatched and unrelated donor cells:

At 180 days after the transplant, 12 percent of patients treated with Velcade had severe acute GVHD, compared to typical 28 percent of recipients receiving unrelated donor cells and 37 percent of transplant patients receiving mismatched donor cells.

Two-year overall survival was 84 percent in patients treated with Velcade compared to historical one-year survival rates of 52 percent for recipients of unrelated donor cells and 43 percent for transplant patients who receive mismatched donor cells.

The medication was tolerated well, with the most serious side effect being mucositis — painful inflammation of the mucous membrane.

“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, the study’s lead author and principal investigator.

Findings from this study were presented at the 2013 American Society of Hematology (ASH) Meeting.

This research was supported by National Cancer Institute and by Millennium Pharmaceuticals, the manufacturer of Velcade and Otsuka Pharmaceutical Co.

Dr. Koreth disclosed financial ties with Millennium Pharmaceuticals and Takeda Pharmaceuticals, the parent company of Millennium.

Review Date: 
December 7, 2013