Even a half-century later, a physician cannot forget the first death of a patient under their care. It happened for me during my postgraduate medical training in the 1970s in an academic medical center hospital in the western half of the United States.
She was a delightful young married woman who was the mother of three small children. She was admitted to the hospital for recurring seizures. Her workup revealed a history of malignant melanoma. The question was whether her seizures were due to a melanoma brain metastasis or to something else that might be more treatable.
Today, a CT scan of her brain would have quickly answered that question. However, the first CT scan performed in the United States occurred one year after her hospital admission. In her case, the metastasis in her brain was so prominent that it showed up on plain X-rays.
The five-year survival rate for metastatic malignant melanoma in those days was less than five percent. However, since our patient’s survival projection was not zero percent, our internal medicine hospital team decided to do everything possible to allow her to be with her children as they grew up.
In those days, the traditional chemotherapy strategies that were available had no significant clinical benefit on metastatic malignant melanoma. As such, we felt that her only chance would be surgical removal of the mass in her brain.
This young woman had a steadfast desire to live. But the only option we could offer her was surgery. After much-heated debate with our surgical colleagues, they finally agreed to perform the surgery (perhaps in part to get our medical team off their backs). While she survived the operation, we later learned that she died about six months after the surgery from complications of metastatic melanoma.
Had this young woman presented with metastatic melanoma today, she would have had a much better chance of long-term survival as a result of immune checkpoint inhibitor therapy.
The healthy human immune system has a number of “stop and go” functions. These functions normally protect our bodies from threats such as infections and cancer cells without overreacting and causing autoimmune disorders. Immune checkpoint inhibitor therapy is a form of drug treatment that takes away all of the “stop” functions in our immune system. That allows our immune system to become more aggressive in seeking out and destroying cancer cells in our bodies.
This morning, I saw a report in the New England Journal of Medicine titled “Final, 10-year outcomes with nivolumab plus ipilimumab in advanced melanoma.” This report was a 10-year follow-up study of 945 international patients who either had or were at very high risk of having metastatic melanoma that had been treated with immune checkpoint inhibitor therapy. Those patients who had been treated with both of the first two immune checkpoint inhibitor drugs, nivolumab and ipilimumab, had a median overall survival of 71.9 months (~6 years) and a median melanoma-specific survival of more than 120 months (10 years). This has been among the most miraculous medical breakthroughs that I have witnessed in my five-decade medical career.
American medicine is increasingly coming under fire because of its ballooning costs. The current annual cost of immune checkpoint inhibitor cancer therapy in the United States ranges from $100,000 to $300,000. The many-headed monster of American health care costs desperately needs to be addressed. Each of the heads of that monster will have to give a little in that upcoming political negotiation. However, when that happens, the babies should not be thrown out with the bath water. One of those babies is the relatively low cost of supporting the academic basic and clinical biomedical research consortium, which is the fragile seed from which modern medical miracles like immune checkpoint inhibitor cancer therapy can flower.
Richard D. Sontheimer is a dermatologist.
