Melanoma shows immunotherapy's promise, limits
When Ms. F first came to my office, I was concerned that I may not be able to help her. At 89, advanced melanoma that had started on her legs had now spread to her lymph nodes, lungs, and bones. Ten years ago there were few options other than chemotherapy – which can be harsh for older people -- and her prognosis would have been poor.
When Ms. F first came to my office, I was concerned that I may not be able to help her. At 89, advanced melanoma that had started on her legs had now spread to her lymph nodes, lungs, and bones. Ten years ago there were few options other than chemotherapy – which can be harsh for older people -- and her prognosis would have been poor.
But Mrs. F – who had few other medical problems and big plans for her 90th birthday and a grandchild's wedding – was in luck. Over the past fifteen years, how we treat advanced melanoma has changed dramatically. There are nine new drugs that are better tolerated by patients and that have better outcomes.
We decided to treat Ms. F with one of the new immunotherapies, an anti-PD1 antibody. When we repeated her imaging studies after just four doses, her melanoma had almost completely disappeared with few side effects.
Not every patient is as fortunate. Around the same time, I saw a 39-year-old patient, Ms. Y. Her case was similar: melanoma that began on her leg had spread to her lung, lymph nodes, and liver. She too received 4 doses of an anti-PD1 antibody but repeat scans were deemed a "mixed response" with some tumors growing bigger and some smaller.
Although Ms. Y continued treatment, after dose 6 she complained of a cough and difficulty breathing due to a sudden inflammation of the lungs -- a worrisome side effect of anti-PD1 antibodies called autoimmune pneumonitis. We stopped the therapy and started high doses of steroids to reduce the inflammation and ultimately moved on to other therapies to treat her progressing melanoma.
Given that a decade ago, very few people survived metastatic melanoma long term, these drugs are nothing short of miraculous for some. As the cancer community works on integrating immunotherapies into treatments, here are a few important things to consider:
1) Side effects: Unlike traditional chemotherapy, which can cause nausea or hair loss, side effects of immunotherapy are much less predictable. Diarrhea, thyroid problems, lung inflammation, rash, liver injury, and pituitary gland problems are all caused by immune cells attacking these body parts along with the cancer. Since each person's immune system is unique, the possibility and timing of such side effects vary person to person.
2) Immunotherapy is not for everyone: Since the side effects result from an overacting immune system, patients with pre-existing autoimmune disorders such as inflammatory bowel disease or lupus should avoid these drugs as they could severely worsen symptoms. Also, though these drugs have been available to patients for the last 5 years, doctors are still figuring out the best ways to monitor and manage side effects. When giving a combination of immunotherapy drugs, side effects can increase and management can be complicated.
3) Not all immunotherapy is created equal: Differences exist between agents as ipilimumab, an anti-CTLA4 antibody, and nivolumab and pembrolizumab that are anti-PD-1 antibodies. There is also another class called anti-PDL1 antibodies, such as atezolizumab. They vary in the way they work, their effectiveness, and their side effects. Numerous other immunotherapy agents currently in clinical trials that may quickly make it to the clinic will also be unlike currently available drugs.
4) Expense: Off the shelf these immunotherapy agents are some of the most expensive drugs that the medical community has ever seen. The cost of ipilimumab remains at $30,000 per treatment and is often given four times, which results in a total cost of around $120,000. Nivolumab, given its variation in duration, has less of a fixed cost but is priced around $12,000-$18,000 per month of treatment. Treatment in some circumstances may extend greater than 24 months. In a recent clinical trial, Ipilimumab was priced at $158,282 (median 4 doses given), nivolumab at $103,220 (median 15 doses given), and the combination at $295,566 (median four doses of each nivolumab and ipilimumab).
While very few patients have to pay these costs, co-pays can still apply. It is important to know that there are many mechanisms for financial assistance provided by drug companies, hospitals, and independent foundations. Patients who are beginning this type of therapy should inquire about options for financial assistance if needed.
5) We will do better: Immunotherapy in melanoma has ignited a scientific revolution and has offered the promise of a cure. There are dozens of clinical trials posing questions that could help reduce side effects and investigating new types of immunotherapies. Success in melanoma has propelled the use of these drugs into many other cancers including lung, kidney, breast, pancreatic, , leukemias, lymphomas, and brain, most of which remain in clinical trials. However, in the past two weeks immunotherapy agents have been FDA approved for both Hodgkin's lymphoma and bladder cancer.
Marlana Orloff, MD is a medical oncologist and researcher at the Sidney Kimmel Cancer Center at Jefferson.
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