Melanoma is no longer a death sentence

Several months ago, my wife, Françoise, and I attended something novel for melanoma patients: a survivors' dinner.

People said they wanted to make it an annual gathering. Planning anything that far in advance had been pointless for me. Two years ago, I was about to accept hospice care.

When I was diagnosed in 1996, very early surgery was the only reliably successful treatment. A more advanced case was essentially a death sentence.

Over the past five years, a series of revolutionary drugs have given me and many other people a surprisingly hopeful prospect. Nevertheless, the drugs' development process has often been excruciating for participants in clinical trials, and the drugs' remarkably high costs limit their value.

My journey begins

I have the most common form of melanoma, which can occur in fair-complexioned people who had blistering sunburns in their youth. I also spent a year in my 20s in the South Pacific, doing biological-anthropological fieldwork, which meant more episodes of particularly intense sun exposure.

My first melanoma lesion revealed itself three decades later — when I was 56 — as a small, irregular raised blue-gray lump above my knee.

When I showed it to a dermatologist, she unceremoniously told me to take off my trousers and lie down on her examination table. As she numbed the area and began to cut, I put my hands over my face.

She said, “Am I hurting you?” No, I said; it was the shock. I knew melanoma was particularly aggressive and lethal.

Follow-up surgery to remove more surrounding skin and a nearby lymph node in my upper thigh revealed no further evidence of disease. The tumor's depth suggested that my prospects were alarming enough: There was a 20 percent chance of recurrence.

In the next few years, I had periodic skin examinations and chest X-rays. Everything looked normal. Of course, anxiety lingered.

A reoccurance

In 2000, as I got up from bed one night, I felt an olive-size lump in the same area that had been biopsied seven years before. The lump was confirmed as a melanoma tumor a few days later.

I was stunned. Statistics suggested that my five-year survival chances had just plummeted to 20 percent.

Everything suddenly became uncertain and threatening. My focus changed. Concerns about world affairs, money, and social and professional status all receded.

After a few days, Françoise, whom I had been dating, said, “Jonathan, you have to take early retirement.” I replied, “And we have to get married.”

We quickly married a few days before I had surgery to remove the entire lymph node bed. For the next five years, my disease continued to spread very slowly.

One oncologist said, “Either your immune system is very smart or your tumor is just very stupid.”

Nevertheless, I underwent two deeper surgeries in my lower right abdomen and joined two ineffective clinical trials.

Stage four

By 2008, Françoise and I had retired to rural Connecticut, and I came under the care of Mario Sznol, leader of Yale University's Melanoma Clinical Research Program.

After carefully reviewing my earlier scans and history, he shocked us with the news that the disease had already spread to my lungs. My melanoma had reached Stage 4. I had a median expected survival of eight months.

Sznol said that chemotherapy or further surgery was pointless; immunotherapy was my best remaining option. However, the two forms available at the time (alpha interferon and interleukin-2) had extremely low success rates.

I was treated with both, and they had no apparent impact on my disease. They did, however, cause nasty side effects. Alpha interferon gave me chills and a bad rash. I felt exhausted and spent most of the day in bed. Interleukin-2 disoriented me and caused me to gain 30 pounds within a week. I ended up in the cardiac ward.

Fortunately, the effects were all quickly reversible. And Sznol said that immunotherapy drugs then in development offered great hope.

Unlike chemotherapy, which simply kills susceptible cells, immunotherapy aims to boost your production of certain white blood cells (the T-cells) that can detect and kill tumors.

One drug showing promise was Bristol-Myers Squibb's anti-CTLA-4 antibody, ipilimumab.

Ipilimumab's journey to the market wasn't easy. Many melanoma patients anxiously followed the drug's slow path through clinical trials, which began in 2000. Because the drug acted differently from chemotherapy, it confused researchers and regulators. In many responders, tumors might initially grow rapidly before slowly melting away, and some unexpected side effects — such as colitis — could be particularly severe, even causing some trial patients to die. Early trials failed to meet expectations, mainly because traditional chemotherapy goals (for example, measurable tumor shrinkage within a month or two) were used for assessment.

The delays were frustrating and demoralizing. In 2010, I and other patients with advanced melanoma were able to get ipilimumab a few months before its FDA approval through an expanded-access program. My side effects were manageable, and 12 weeks after I began treatment, scans showed clear signs that my tumors had begun to shrink

Optimism suddenly returned in a rush — perhaps I would survive after all. However, I was not one of the truly fortunate 10 percent of treated patients who became completely tumor-free. After a year and a half, new tumors began to appear in my brain, lungs, intestines and abdomen. The cancer was metastasizing throughout my body.

Unsuccessful trials

My hope now centered on another immunotherapy checkpoint inhibitor. In 2008, Bristol-Myers Squibb had begun clinical trials for an anti-PD-1 drug that appeared to produce better survival rates than ipilimumab. The initial clinical trial I tried to join was oversubscribed, and I was excluded from later ones either because I'd had a questionable biopsy for prostate cancer or because I'd had previous immunotherapy treatment.

My frustration and despair mounted. The growing tumors now began to cause discomfort in my intestines, muscles and lungs. I required almost weekly blood transfusions because of internal bleeding. I tried a second and third round of ipilimumab, with modest effects, and another experimental anti-PD-1 drug. In April 2013, I tried a chemotherapy trial in Nashville.

Nothing worked. I began to accept my imminent death.

Surgery

I joined a trial for Merck's competing anti-PD-1 drug, pembrolizumab. I flew to the Mayo Clinic in Jacksonville, Florida, twice in May 2014 for infusions. By then, I was too weak to walk through airports, and Françoise had to push me in a wheelchair.

I transferred my pembrolizumab treatment to Yale as soon as it was offered there, in June 2014. Tumors were intermittently blocking my small intestine, causing severe cramping and vomiting. An uncomfortable tube was inserted into my stomach via my nose. I was now in and out of emergency departments, taking opiates and hoping for a quick response to the drug. However, the blockages did not resolve themselves.

I was hospitalized, receiving nourishment via IV infusion only, and a second tube was inserted directly into my stomach. I had arrived at death's door.

I was offered abdominal surgery to remove the obstructing tumors in my intestines. While others were pessimistic, Sznol said that there was a real chance the drug could eliminate the remaining disease after the surgery. Although things might “go the other way,” he said, there was the potential for me to regain a normal life. That was a prospect we couldn't refuse.

The operation was unexpectedly rough. My intestine had perforated en route to the operating room and was starting to leak stool. If the team had waited a few hours longer, I would have died from an infection. They removed almost a yard of intestine and created an ileostomy — a diversion of my small intestine through an opening in my abdominal wall, bypassing my colon.

I awoke in excruciating pain and was distraught when they told me how the operation had gone. I told the surgical team I didn't want to live. Everyone suddenly became quiet.

The surgeon leaned over me and said: “Dr. Friedlaender, you will be out of most of the discomfort and off the opiates in a couple of days. The tubes to your stomach will come out, the IV nutrition will stop and very soon you'll be able to eat again. In two weeks, you should be able to go home as you've wanted so badly.”

My recovery at home was difficult. I was very weak after almost six weeks in the hospital. Françoise became my constant nurse. I slowly regained my strength and began to take care of myself. My next scans showed that I was responding to the drug, and the prospect of imminent death immediately receded.

Two years after my crisis, I have one remaining pea-size tumor in my armpit. It will probably continue to shrivel away. I just stopped taking the anti-PD-1 drug last month. When I die, Sznol says, it will be from something besides this horrible disease that I have come to know so intimately.

During the long struggle, I experienced both remarkable and distressing aspects of the U.S. health care system. I am trying as best I can to contribute to the correction, improvement and humanization of that system. Everything has changed in my life. There is much to appreciate and savor, and much more to do.

• Friedlaender is an emeritus professor of biological anthropology at Temple University in Philadelphia. This article was excerpted from the journal Health Affairs and can be read in full at healthaffairs.org.