Treatment-Related Hyperprogression: Concerns Continue to Mount

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Evidence is growing to support the idea that immune checkpoint inhibitors can speed up tumor growth, although the exact mechanism of how this occurs is still unclear.
Evidence is growing to support the idea that immune checkpoint inhibitors can speed up tumor growth, although the exact mechanism of how this occurs is still unclear.

Approximately 3 months ago, a cancer patient traveled a few hundred miles to see medical oncologist Razelle Kurzrock, MD, chief of the hematology and oncology division in the UC San Diego School of Medicine, California. The patient had cancer and he knew what he wanted: immunotherapy.

“Sometimes patients have their own ideas of what they want to be treated with,” Dr Kurzrock told Cancer Therapy Advisor. She explained to the patient that based on what she knew, he was actually a bad candidate for immunotherapy; his tumor had an MDM2 amplification.

Dr Kurzrock does not treat patients with single-agent immune checkpoint inhibitors if their tumors have MDM2 amplification or epidermal growth factor receptor (EGFR) mutation because she and her colleagues found that these abnormalities are associated with a phenomenon called hyperprogression.1 Hyperprogression is a relatively new and controversial term to describe tumor growth that violently speeds up during treatment with immune checkpoint inhibitor therapies. Different from pseudoprogression, tumors that hyperprogress are linked to poor survival and worse clinical symptoms.

Studies have sought to pin down patient or tumor characteristics that predict which patients are at the highest risk for tumor hyperprogression during immune checkpoint inhibitor therapy, but no widely accepted predictors have been identified. Not even advanced disease stage or poor performance status at baseline have been associated with hyperprogressive disease.2 MDM2 amplification and EGFR mutation are the only suspected predictors.

When Dr Kurzrock recommended a treatment other than immunotherapy, the patient who had traveled so far to see her refused her advice and sought treatment elsewhere. Eventually, the patient returned to Dr Kurzrock with displeasing news: his tumor had hyperprogressed during treatment with pembrolizumab. The tumor, he told her, almost seemed as if someone had lit a fire underneath it.

Oncologists who have observed the phenomenon firsthand are starting to share ad-hoc stories like Dr Kurzrock's. Timothy Chan, MD, PhD, vice chair of the Department of Radiation Oncology at Memorial Sloan Kettering Cancer Center, New York, recalls a patient's tumor growing 20-fold larger in about 2 weeks after the start of immune checkpoint blockade. “It resulted in massive tumor growth that eventually caused a lot of issues,” he told Cancer Therapy Advisor. He wasn't sure hyperprogression was real until he saw this particular case. “I have personally never seen a tumor grow this fast before.”

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