Immunotherapy combo halts rare, stage 4 sarcoma in teen
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A patient with end-stage and rapidly progressing soft-tissue cancer whose tumor did not respond to standard treatment, had a "rapid and complete response" to a novel combination of immunotherapy, according to new research.

The immunotherapies targeting the immune checkpoints T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) were administered to a 19-year-old patient with stage 4 epithelioid sarcoma. The patient, whose tumor responded within two weeks after receiving the combination, resumed normal activity and was in a complete remission at the time of the report. The single case was reported online in the Journal of Immunotherapy.

"Epithelioid sarcoma is a rare cancer, and the outcome was not expected to be so positive, the breakthrough in this patient's care was the result of the close collaboration between clinician scientist of the Consortium to elucidate the underlying mechanisms that suggested potential sensitivity to the checkpoint inhibitors", said researchers.

The patient was first diagnosed with the soft-tissue sarcoma along the spine in 2017, as a 17 year old. Chemotherapy, radiation and standard of care drugs, were administered, and surgery was performed to achieve partial response. The patient was admitted to the hospital in April 2019 in severe pain and his cancer had progressed to stage 4.

Most cases of epithelioid sarcoma show an inactivation of a protein-coding gene known as SMARCB1. That inactivation leads to the suppression of INI1, a gene that codes for a tumor-suppressing protein, effectively causing a biological chain reaction that promotes tumor growth.

The doctors obtained a compassionate use authorization to try two checkpoint inhibitors, ipilimumab (anti-CTLA4) and nivolumab (anti-PD1) in May 2019. By October, the patient was in complete remission. As of his last visit in June 2020, he has resumed normal activities and normal physical examination and is essentially asymptomatic.

According to the report, the patient's tumor was reliant on the lack of INI1. But the checkpoint inhibitors apparently unmasked the immune system, making the cancer cells susceptible to the body's natural defenses again.

Source: https://journals.lww.com/immunotherapy-journal/Abstract/2020/11000/Rapid_and_Complete_Response_to_Combination.4.aspx
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