(Brett Ryder/Courtesy of Health Affairs)

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.

Diagnosis and treatment

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.

I was not yet ready to die. I began to make decisions about things I had avoided or neglected. I resolved to get divorced, something my then-wife and I had been considering for years. The stress of cancer is like a gale: It drives distant couples further apart and compels already close ones to cling more tightly together.

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

Metastasis

By 2000, I had gotten divorced and met Françoise, a theoretical chemist, shortly after we had both entered the new world of online dating. We became a devoted couple over the next three years.

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. I sat back down heavily and whispered a curse, waking Françoise. She wondered what was wrong — a nightmare, perhaps? I knew it was far worse.

The lump was confirmed as a melanoma tumor a few days later. We were 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 said, “Jonathan, you have to take early retirement.” I replied, “And we have to get married.” Again, delay made no sense. 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.

Immunotherapy

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, particularly something called anti-PD-1. (“PD” stands for “programmed death.”) It had just begun clinical trials.

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. The old immunotherapy strategy of giving patients high doses of the molecules (such as interleukin-2 and alpha interferon) that normally stimulate T-cell production rarely worked because the immune system has its own brakes, or checkpoints, that prevent the accumulation of very high levels of these molecules.

In the 1980s, James P. Allison at the University of California at Berkeley realized that a better strategy was to block or inhibit the checkpoints themselves, taking the normal brakes off the body’s T-cell production. Almost 30 years after his group identified such a major checkpoint in mice (the CTLA-4 protein receptor), its blocking antibody finally gained approval from the Food and Drug Administration for use in humans with advanced melanoma. This drug is 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. For support, Françoise suggested that I join the online forum of the Melanoma International Foundation, or MIF. The forum helped patients in their searches for promising clinical trials. Nevertheless, my tumors were spreading, and most of the patients I came to know and care about on the forum died.

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. Although I had no painful symptoms yet, the cancer was metastasizing throughout my body.

Anti-PD-1

My hope now centered on another immunotherapy checkpoint inhibitor, the anti-PD-1 drug that Sznol had mentioned to me years earlier. 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 (like so many men my age) 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. Nothing worked.

I began to accept my imminent death. I had lived the life I had desired. I had found my life’s companion and confidante. I had repaired some frayed family relations. I had even lived to see a granddaughter born.

In April 2013, Catherine Poole, the founder of MIF, suggested that I try a novel chemotherapy trial in Nashville. I flew to Nashville for treatments periodically during the next 10 months. However, after I’d had a good response to the drug for seven months, the cancer recommenced its relentless advance.

Crisis and recovery

A few months later, Poole told me that an expanded access program for Merck’s competing anti-PD-1 drug, pembrolizumab, had just begun for advanced melanoma patients. I was able to join the trial and flew to the Mayo Clinic in Jacksonville, Fla., 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. However, the attending surgeon was hesitant because other tumors would remain and grow. Another attending physician was clearly pessimistic. But 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. When the surgical team opened my abdomen, my intestines popped out on my belly from the accumulated pressure. 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.” It was also possible that the ileostomy would be reversible in time.

Françoise reminded me that it would take another month to know whether the anti-PD-1 drug was working and said that I should not lose hope. This calmed me.

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.

Reforming clinical trials

During this 20-year journey, I learned a good deal about drug development and approvals. I also became an FDA patient representative , which taught me even more.

Immunotherapy drugs are among the greatest recent successes in drug development. The approved combination therapy of an anti-PD-1 drug and ipilimumab for advanced melanoma has had “stunning” effects, according to Harriet Kluger of Yale. Immunotherapy drugs have been approved or are in trials for more than 30 other solid-tumor malignancies. Cancers of the kidney, bladder and lung, as well as refractory Hodgkin’s lymphoma, have all been shown to respond to anti-PD-1 drugs to different degrees.

The number of new drugs approved by the FDA has been increasing in the past three years, and 51 were approved in 2015 — the highest number since 1950. This is because the agency has developed a number of ways to accelerate approvals of promising drugs.

A small and relatively short trial with appropriately designed goals can now support a provisional approval, followed by close monitoring in the clinical setting. This means waiving the randomized double-blind final trial that has been the FDA “gold standard” since the thalidomide scandal more than 50 years ago. Such trials have become a cumbersome, multibillion-dollar enterprise. I also believe that those patients faced with imminent death have the right to risk their lives by taking a safe and promising, but not yet approved, drug, just as they have the right to decide when to terminate further treatment.

Drug costs

I was amazed by the prices of new medications and how they vary. My insurance paid $153,000 for 17 infusions of my drug during a year. However, the price for a friend who received identical treatment through another insurance plan was four times as much — about $600,000. The difference is apparently because my insurer’s negotiating group was bigger and had more leverage.

Commenting generally on drug pricing, a group of more than 100 experts on chronic myeloid leukemia concluded in a May 2013 article in the journal Blood: “Of the many complex factors involved, price often seems to follow a simple formula: start with the price for the most recent similar drug on the market and price the new one within 10 percent to 20 percent of that price (usually higher).”

Drug companies simply charge what they think the market will bear.

A survivor’s perspective

I have been incredibly fortunate. My disease was especially indolent. I was able to retire early and look for promising clinical trials. I certainly could not have survived without the continuing support of my wife. I was treated in an outstanding university teaching hospital that had expertise in immunotherapy, and I had comprehensive health insurance.

My multiple surgeries, plus the expensive drug treatments, were enough to bankrupt almost anyone without coverage. My biggest out-of-pocket expense was commuting to Nashville for 10 months, which totaled $8,000.

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.