Establishing the Carcinogenic Risk of Immunomodulatory Drugs

Abstract

The first effective immunosuppressive drug (ISD) was azathioprine, approved in 1968. Early experience with this drug suggested that patients might have an excess risk of tumors including lymphoma and skin tumors. Comparison among various registries has shown that the cumulative risk of tumors increases over time. The risk is additionally increased by the more intense immunosuppressive regimens needed for lung or heart-lung transplants. The link between immunosuppression and tumorigenesis was further reinforced by the high concordance of tumor types between transplant and HIV patients. The role of the immune system in tumor defense includes both direct tumor surveillance and immunity against oncogenic viruses. In transplant patients, at least two-thirds of the lymphomas are Epstein-Barr virus (EBV)-positive. Existing methods of testing for carcinogenicity are not considered adequate to identify the hazard of tumorigenesis due to these drugs. Research is ongoing in Food and Drug Administration laboratories and at collaborators' laboratories to evaluate experimental systems that may have the ability to adequately identify this class of hazard. Initial work is on various model systems similar to EBV. These include the MHV-68 mouse model, lymphocryptovirus (LCV-1) in the cynomolgus monkey, and preliminary work with mice with humanized immune systems using EBV directly.

Induction intravenous cyclophosphamide followed by maintenance oral immunosuppression in refractory myasthenia gravis

“…Perhaps most feared is the increased risk of malignancies, such as leukemia, lymphoma, skin cancer, and solid malignancies . It is worth noting, however, that all patients on long‐term immunosuppression, including our treatment‐refractory MG cohort, are likely at increased risk of malignancy independent of CYC treatment (as reviewed elsewhere). The risk of CYC toxicity is related to the cumulative dose, duration of therapy, and route of delivery.…”

Limited Risks of Major Congenital Anomalies in Children of Mothers With IBD and Effects of Medications

“…Inflammatory bowel disease (IBD) commonly affects women of reproductive age 1 , and is often managed using drugs recognised to have potential for toxicity in adults 2,3 . Since it is unethical to test the safety of almost all drugs in pregnancy in clinical trials, the potential for teratogenicity of drugs taken during pregnancy has been a pressing and natural concern of all pregnant women or those attempting to become so.…”

Anti-tumour effects of polysaccharides isolated from <i>Artemisia Annua</i> L by inducing cell apoptosis and immunomodulatory anti-hepatoma effects of polysaccharides

“…Essentially, tumorigenesis is due to the attenuation of body's immune-defence system, which makes the cancer cells escape attack by the T cells (Weaver, 2012;Foster et al, 2011). Therefore, the stimulation of immunomodulation by reagents will contribute to the elimination of cancer cells in cancer immunotherapy (Han et al, 2006).…”