Immunotherapy for GU Ca: A primer for urologists
“Compared with vaccines that work by pressing the accelerator on the immune system, the CPIs work by releasing the brakes on the immune system. CPIs have produced some very exciting results in terms of improving overall survival and producing durable responses in patients with advanced renal and bladder cancer,” said Dr. Kim, co-medical director of the Urologic Oncology Center, Cedars-Sinai, Los Angeles.
“Not only can the CPIs shrink the tumor, but it has been suggested that immunotherapy can alter the long-term growth kinetics. In other words, tumor growth may occur at a slower rate, and that too can translate into improved survival.”
Dr. Kim also pointed out some unique pharmacodynamics characteristics of the immunotherapies. For example, improved survival with sipuleucel-T is not accompanied by a PSA response, and early imaging in patients with UC or RCC treated with a CPI may show the tumor size is increased.
“However, the change may not be a sign of tumor progression. Instead, it may represent a pseudoresponse in which immune cells have infiltrated the tumor,” Dr. Kim explained.
In addition, whereas the effect of chemotherapy persists only as long as the drug is in the body, the anti-tumor effect of immunotherapy may continue after the treatment is stopped, mediated by the activity of memory T cells.
The modern immunotherapy agents have a different and better safety profile than that of chemotherapy and with IL-2.
“Interleukin-2 has good clinical activity as treatment for mRCC in selected patients, particularly those with pulmonary metastases, but it can be fairly toxic with the potential to cause shock and hypotension,” said Dr. Petrylak, professor of medicine and urology, Yale School of Medicine, New Haven, CT.
Among the immunotherapy agents approved for genitourinary malignancies, sipuleucel-T is probably the best tolerated. Its most common adverse events are chills, fatigue, fever, back pain, nausea, joint ache, and headache.
The adverse events most commonly associated with CPIs arise from activation of the host immune system and include immune-mediated colitis, dermatitis, hepatotoxicity, hypophysitis, and hypothyroidism. With prompt recognition and timely management using immunosuppression and temporary dose modification or treatment interruption, the severity of these toxicities can be limited, and they are usually reversible.
“It is important to monitor patients for the immune-related adverse events, but it is interesting that some studies of immunotherapy found that development of autoimmune toxicity corresponded with a better anti-tumor response,” Dr. Kim said.
Adverse events associated with the CPIs targeting the PD-1/PD-L1 axis appear to be less severe than those occurring with anti-CTLA-4 antibodies.