CellCept linked to reduced cancer incidence

Apr 23 2004

A study presented today at an international transplant meeting showed that heart transplant patients treated with the immunosuppressant CellCeptÒ (mycophenolate mofetil) in standard immunosuppressive regimens had a significantly lower risk of developing cancer compared to those receiving non-CellCept-based treatment regimens.

Presented at the annual meeting of the International Society for Heart and Lung Transplantation (ISHLT), the study found a 27% lower risk of cancer in CellCept-treated patients. Patients studied were part of the ISHLT Transplant Registry.

“Though not derived from randomized controlled trials, these data indicate that the choice of maintenance immunosuppressive regimen may be a modifiable risk factor for the development of malignancy in heart transplant recipients,” said James O’Neill, M.D., Fellow in Heart Failure and Cardiac Transplantation, Cleveland Clinic.

Previous research had shown that organ transplant recipients receiving immunosuppressive therapy are three to four times more likely to develop tumors than the general population and have an even greater risk of developing certain rare cancers.

Extensive Examination of Registry Validates CellCept Treatment
The study, Mycophenolate Mofetil and the Risk of Developing Malignancy Following Orthotopic Heart Transplantation (OHT), examined competing risk factors to determine which are associated with malignancy following OHT, and was based on 3,895 patients in the ISHLT Transplant Registry. The study examined survival without malignancy in patients taking standard immunosuppressive regimens (defined as cyclosporine or tacrolimus and azathioprine or CellCept), who underwent OHT between January 1, 1995, and December 31, 1997.

Of these patients, 703 (18%) developed malignancy during the follow-up period through June 30, 2002. The breakdown of malignancy was as follows: skin (47%), post-transplant lymphoproliferative disease (10%), other malignancies (33%), unreported (10%).

Independent predictors of significantly increased risk were a pre-transplant history of cancer and increased age, while the use of CellCept was significantly protective (27% lower relative risk; 95% confidence interval: 0.56-0.95; P-value: 0.02). Relative to the mean age of 55 years, the risk of malignancy for 30, 45 and 60 years of age was 0.32, 0.46 and 1.37 respectively. Female gender was associated with a 32 percent reduced relative risk. Neither OKT3 nor ATG use was associated with an increased risk of malignancy. These findings build on the results from two studies presented at last year’s American Transplant Congress, in which kidney transplant patients treated with CellCept were not significantly more likely to develop lymphoma/post-transplant lymphoproliferative disorder (PTLD) than those patients who were not exposed to the drug.

“Data such as these are critical to increasing our understanding of the risks that follow organ transplantation,” said Dr. O’Neill. “The better we can manage those risks, the better the patient’s long-term prognosis.”

About CellCept
CellCept is an immunosuppressant or anti-rejection drug used in combination with other immunosuppressive drugs (cyclosporine and corticosteroids) for the prevention of rejection in patients receiving heart, kidney and liver transplants. CellCept received FDA approval for the prevention of organ rejection in kidney (May 1995), heart (February 1998), and liver (July 2000). The recommended dosages for CellCept follow: for adult kidney transplants, 2 g daily; for pediatric kidney transplants, oral suspension 600 mg/m2; for adult heart and liver, 3 g/day.

The principal adverse events associated with the administration of CellCept (in combination with cyclosporine and corticosteroids) include diarrhea, leukopenia, sepsis and vomiting, and there is evidence of a higher frequency of certain types of infections. A higher proportion of renal transplant patients in the active treatment groups experienced one or more opportunistic infections compared with patients receiving placebo. Cytomegalovirus tissue invasive disease was more common in patients receiving 3 g/day.

Increased susceptibility to infection and the possible development of lymphoma and other malignancies, particularly of the skin, may result from immunosuppression. Only physicians experienced in immunosuppressive therapy and management of renal, cardiac or hepatic transplant patients should use CellCept. Patients receiving the drug should be managed in facilities equipped and staffed with adequate laboratory and supportive medical resources. The physician responsible for maintenance therapy should have complete information requisite for the follow-up of the patient.

There are no adequate and well-controlled studies in pregnant women. However, CellCept has been shown to have teratogenic effects in animals; it may cause fetal harm when administered to a pregnant woman. Therefore, CellCept should not be used in pregnant women unless the potential benefit justifies the potential risk to the fetus. For full prescribing information, visit http://www.rocheusa.com/products/cellcept/pi.html.

About Roche
Hoffmann-La Roche Inc. (Roche), based in Nutley, N.J., is the U.S. prescription drug unit of the Roche Group, a leading research-based health care enterprise that ranks among the world’s leaders in pharmaceuticals and diagnostics. Roche discovers, develops, manufactures and markets numerous important prescription drugs that enhance people's health, well-being and quality of life. Among the company’s areas of therapeutic interest are: genitourinary disease; infectious diseases, including influenza; inflammation, including arthritis and osteoporosis; metabolic diseases, including obesity and diabetes; neurology; oncology; transplantation; vascular diseases; and virology, including HIV/AIDS and hepatitis C.

For more information on the Roche pharmaceuticals business in the United States, visit the company’s web site at: http://www.rocheusa.com