OPTN/UNOS Data Show Newer Transplant Therapies Associated With Lower Cancer Incidence Rates

Patients receiving mTOR inhibitors exhibit fewer early malignancies than those receiving Cyclosporine-Based regimens

May 16, 2004

BOSTON/PRNewswire

Authors: H. Myron Kauffman, M.D., Wida S. Cherikh, Ph.D., Yulin Cheng, Douglas W. Hanto, M.D., Barry D. Kahan, M.D., Ph.D.

New data presented today from the OPTN/UNOS (Organ Procurement and Transplant Network/United Network for Organ Sharing) database show that the relative risk of developing cancer following transplantation is substantially reduced in patients receiving maintenance immunosuppression with mTOR inhibitors as compared to patients receiving treatment with traditional calcineurin inhibitors. Conventional immunosuppressive therapies, like cyclosporine or tacrolimus, can be associated with high rates of cancers, resulting in late death for a number of transplant recipients.

These are the conclusions of a study presented by researchers from the United Network for Organ Sharing (UNOS) and other institutions at the American Transplant Congress, a combined scientific session of the American Society of Transplant Surgeons and the American Society of Transplantation, held at the Hynes Convention Center in Boston.

"We know that transplant patients have a greater risk of developing cancer than the general population, and unfortunately excessive immunosuppression, particularly with certain drugs, is a substantial contributing factor," said Dr. H. M. Kauffman, a Senior Research Scientist at UNOS. "As newer drugs have become available, and new innovative regimens are developed, we wanted to see if they could impact this cancer rate. This is the largest analysis of its kind, comparing the different regimens, and it clearly shows that the mTOR inhibitors offer a significant benefit in reducing short-term malignancy rates in transplant recipients."

The retrospective study looked at more than 33,000 people who received a primary solitary kidney transplant between 1996 and 2001. The data showed that only 0.65% of those treated with the mTOR inhibitors (more than 97% receiving sirolimus) developed new cancers during the two years of follow up. This was significantly lower than patients treated with calcineurin inhibitors (cyclosporine or tacrolimus, 1.83%; p<0.001).

In a risk adjusted multivariate analysis, patients treated with mTOR based immunosuppressant therapy had a 59% reduced relative risk of developing new cancers (relative risk 0.412, 95% CI 0.256, 0.663) than those given calcineurin-based therapy. This was a highly significant reduction in relative risk (p=0.0003).

"These short-term results will need to be both evaluated long-term and be evaluated in other transplanted organs such as liver, heart, and lung," said Dr. Kauffman.

Animal evidence suggests that conventional calcineurin immunosuppression promotes rather than inhibits the development of cancer. Calcineurin inhibitors have been shown to induce cancer progression and increase transforming growth factor-B (TGF-B) expression that is associated with cellular changes that are characteristic of invasiveness. In contrast, mTOR inhibitors appear to have a negative growth effect on malignant cells. mTOR inhibitors, in animals, reduce TGF-B and vascular endothelial growth factor (VEGF) expression and inhibit tumor angiogenesis.

About Malignancies and Transplantation:

• Transplant recipients have an increased risk of developing cancer in general (one to two per cent per year) and a 15-20 fold higher incidence of certain types of cancer. The general incidence of all malignancies after kidney transplantation increases with advancing time and seems to be dependent on both duration and intensity of immunosuppression.
• Skin cancer and post transplantation lymphoproliferative disorders such as non-Hodgkin's lymphoma are the most prevalent types of cancer seen post transplantation. The risk of cervical, breast cancer and colorectal cancer are also increased.

About UNOS

• A private, nonprofit organisation, UNOS manages the nation's organ transplant system and oversees the world's most comprehensive database of clinical transplant information under contract with the federal government. UNOS operates the 24-hour computerised organ sharing system, matching donated organs to patients registered on the national organ transplant waiting list. UNOS seeks to increase organ donation through education and improve transplant success rates through outcomes-based research and policymaking. The strength of the transplant database relies on the conscientious reporting of 469 UNOS member institutions. This work was supported in part by Health Resources and Services Administration Contract +1-231-00-0115.

Distributed by PR Newswire on behalf of United Network for Organ Sharing

Copyright © 2004 PR Newswire Europe Limited.

This article posted July 9, 2004.