An Elegant Defense

by Matt Richtel

  “Love you, man,” Jason said. He’d started telling his friends he loved them. This was uncharted language for a group of Colorado boys steeped in jock culture.

  The end was near.

  On March 4, Jason came for his regular visit. Dr. Brunvand examined him, with Poppy Beethe, Jason’s longtime oncology nurse navigator, looking on. Empathy poured from her face, punctuated by eyes that mist up when she watches sappy commercials. She’d grown to cherish Jason.

  He was complaining of a new symptom, pain and swelling on the left side of his chest and back.

  Dr. Brunvand had a good idea what that meant, and he began feeling the weight of his own emotions. He gave Jason a broad clinical exam and discovered Jason couldn’t move his inflamed left hand, with the muscles impinged by the tumor’s growth into the nerve that fed them. He looked jaundiced. It was hard to hear Jason breathe on the left side, and his inhalations cackled. His skin was leatherish and discolored from his left pelvis to his left shoulder.

  “Jason, will you excuse me for a moment?”

  Dr. Brunvand opened the door of the boxy exam room, closed it behind him, and stood for a moment in the hallway, arms crossed. This was going to be very difficult. He took several deep breaths. He went back into the exam room and pulled up a stool beside Jason, sitting in the oversized chemo/exam chair.

  “Jason, you are going to die.”

  Jason started to cry. Poppy started to cry.

  “As your friend, it’s my job to make you as comfortable as possible.”

  Jason knew one thing for sure. Dr. Brunvand wasn’t a quitter. Dr. Brunvand was built to be Jason’s oncologist, the two of them a pair who would sweat together and sprint, climb, and fight, and not give up or in. This oncologist wouldn’t say the words “You are going to die” unless Jason had reached the end.

  “There’s nothing left to treat you with. Chemotherapy is doing more harm than good.”

  Jason cried.

  “Jason, do you understand what I’m saying?”

  He nodded.

  “I’d like to get your family here as soon as possible to talk about next steps.”

  “What about that one drug?”

  That one drug was called nivolumab. It was leading-edge immunotherapy. It had been approved by the FDA in 2014 for treatment of late-stage melanoma. The drug unleashes the body’s immune system. It’s a monoclonal antibody treatment built on the shoulders of all the years of immunology, and it works by disrupting cancer’s nasty trick of bringing our elegant defenses to a standstill. At the time, the drug was not approved for use in Hodgkin’s lymphoma, Jason’s cancer.

  But also in 2014, an article in the New England Journal of Medicine presented powerful evidence that the nivolumab could prolong life for Hodgkin’s patients. The article highlighted just twenty-three cases of increased survival in a clinical trial of patients with late-stage Hodgkin’s, but the findings gave a sliver of hope where there had been no hope at all.

  Jason’s brother-in-law, Paul, and Dr. Brunvand had previously discussed the treatment, known as a PD-1 inhibitor. Dr. Brunvand told Jason he’d bring information about the “experimental treatment” to the family meeting, planned for the following Friday. By all rights, it would be a meeting to tell Jason’s family to get ready to say goodbye.

  Jason carried his wisp of himself back to his van.

  In his doctor’s notes, Dr. Brunvand had outlined what he’d tell the family. “The most reasonable approach at this point, as emotionally taxing as it is, is to consider Mr. Greenstein for hospice care,” he wrote. “Palliative or supportive care would be another option, in which he can get transfusion support, but not be resuscitated and not receive any more chemotherapy.”

  In the intervening days, Dr. Brunvand planned for an “end of life” talk. He also spoke to a clinic administrator to find any loopholes that might allow Jason to take nivolumab. Merck agreed to allow Jason to take what was called a drug replacement, basically allowing a onetime exception under extraordinary circumstances. The hospital would not “mark up” the drug and the company would provide them with a free replacement dose for each subsequent dose Jason might receive.

  Still, someone would have to pay for the initial dose. Plus, Jason was in such poor health that he wasn’t even an ideal candidate, as Dr. Brunvand was poised to explain to the family.

  The whole Greenstein clan gathered in a vanilla conference room at the clinic. The mood was bleak. Dr. Brunvand explained Jason’s condition. They talked about the likely outcome. The question on everyone’s minds was: How much time does he have? No one put it so finely, but the answer was that he had weeks, maybe a few months, to live.

  At the meeting, Dr. Brunvand explained about the Hail Mary treatment, nivolumab. He told them that the evidence in the New England Journal of Medicine was not enough data for FDA approval, and informed consent would be required to begin a treatment with the drug. It was “experimental” at best, but had few toxicities compared to the deluge of prior therapy he had endured. Before Jason could receive this type of treatment, he had to understand fully the unknowns.

  “Jason, you don’t have enough platelets to do any treatment, and it’s not approved.” Platelets help the blood to clot and contribute to inflammation. To start treatment, he’d need a platelet count of 75,000, preferably, but maybe could get away with 50,000. His count was 8,000, indicating that Jason’s marrow had been damaged by the years of relentless chemotherapy. If they could get the platelet count up, they could try. Cathy said of course she’d pay for a first dose. Jason didn’t need much convincing, but Dr. Brunvand gave him a pep talk, reminding him of a story from Denver Bronco lore. The Broncos were in Cleveland facing the Browns in the 1987 AFC Championship Game. The Broncos needed to go 98 yards in two minutes. One of the Broncos is reported to have said in the huddle, “Boys, we have them right where we want them.” The Broncos won.

  Anyone for a miracle?

  50

  Jason Rises

  It was March 13, a Friday, when Beth drove the shell of Jason for his first treatment of nivolumab.

  He sat in that same chemo chair he’d sat in dozens of times. But this time the clear fluid dripping into his central line was not napalm but nivolumab, the product of decades of profound random investigation and learning about the immune system.

  That night Jason attended his nephew’s basketball game with a former teammate who wondered if the Steel Bull would make it through the night. He did. And the next. Beth stayed with him, his partner to the end. This was hospice, in effect, with a drug that wasn’t yet approved for Hodgkin’s lymphoma. It was anyone’s guess. Jason made it another night, and then another.

  About ten days later, Beth woke up and looked at Jason’s back, where the lump had once so protruded she had lovingly called him Quasimodo.

  “Jason, get up!”

  “What?”

  “Jason, you’re not going to believe this!”

  He wiped sleep from his eyes.

  His tumor was disappearing.

  Beth, Jason’s girlfriend, used her phone camera to chronicle the disappearance of Jason’s tumor after he underwent immunotherapy treatment. (Beth Schwartz/New York Times)

  Dr. Brunvand’s note reads: “Jason was given three doses of nivolumab”; subsequent PET and CT scans performed on April 27 “revealed a complete remission.”

  That’s the medical speak. Here’s how it sounded in human terms when Jason went for his follow-up appointment. Everyone had a different exclamation, many with expletives.

  “What the f*** happened to my cancer? It went away!” he told Dr. Brunvand.

  Beth asked the nurse why Jason had lost so much weight. “Because his tumor has gone,” she was told. “Oh, right,” Beth said, “it really was fifteen pounds.”

  “There was this tiny, nonscientific part of me that thought, if this crazy story is going to happen to anybody, it’s going to happen to Jason,” said Maikovich-Fong, his therapist. He “just has this spirit.”

>   “In all my years,” reflected Poppy Beethe, “I’ve never seen anything like this.”

  Dr. Brunvand offered up his response. “I watched the moon landing in 1969, and it was a similar sense of awe,” he said. “It was with that same sense that we’d crossed a threshold. “I’d just seen the power of the immune system.”

  It was at this point that I picked up my pen. Could this be real? Could someone rise from the dead? Not just someone, but a close friend, someone I’d come to cherish and connect to, a person I’d watched fight and wither, and now soar into the realm of miracle. I felt like I’d seen cancer’s Neil Armstrong, and a giant leap for mankind.

  51

  Apollo 11

  If you land on the moon, you still have to get home.

  52

  Home

  There wasn’t lots of time to celebrate. Now came the nuts and bolts of hardening Jason’s recovery and returning him to health.

  Shortly after Jason went into remission, he got a stem cell transplant from his sister Jackie. The idea here was to give Jason a new immune system, his sister’s, which in theory would be better able to fight any cancer, should it return. After all, Jason’s own immune system had proven lackluster at fighting his strain of Hodgkin’s lymphoma, so perhaps he’d be better off with a slightly different elegant defense.

  This is a high-risk treatment. Think of it: Jason’s own immune cells were removed. In their place were implanted the immune cells of someone else, a foreign presence now swarming him and playing the role of his elegant defense. His life’s festival had been crashed by an alien immune system.

  So it’s no wonder that his subsequent medical report read: “He has had complications.”

  What followed was a severe bout of graft-versus-host disease. His body sought to reconcile itself to this new potentially lifesaving presence before his reaction to it would kill him.

  In July, he suffered a localized relapse of cancer, about a 1-centimeter-wide lump in the skin of his right chest. It was irradiated, and again, the lymphoma responded and no other sites of disease appeared. This didn’t mean that the immunotherapy had failed. Rather, doctors were now helping Jason thread an almost impossible needle. They had to suppress an immune response enough to keep graft-versus-host disease from killing him, while also keeping the immune system strong enough to fight a cancer emergence. Jason felt like he was on the gallows.

  We were talking every few days. I’d gotten the idea of telling Jason’s story in the New York Times as an intimate look into the new immunotherapy phenomenon. I broached it with Jason, and he was thrilled by this idea. It was another adventure for him, and a way to squeeze out lemonade. “Maybe it will help someone to hear my story,” he said. He felt guilty that his cancer experience had so taxed the time, emotions, and resources of his mom and family, and that Beth had given so much. He allowed me unfettered access to his medical records and his doctors. Unvarnished truth. “I want to give something back.”

  On August 13, 2015, when I was in Denver with my family visiting the in-laws, Jason rolled up in his Windstar. He wore baggy orange shorts, a T-shirt, Ray-Ban sunglasses. My father-in-law later asked me if he had AIDS.

  “Sorry I’m late,” Jason said. “My mom and I had a huge fight—screaming and everything.”

  We sat in the backyard and Jason started to sob. “I haven’t cried in a while, and the last three mornings I just sobbed. Ever since I found out the cancer is back. It’s like the fifth time. No matter how many times they tell you you’ve got cancer, it’s still a bad fucking day.”

  Meredith, my wife, a doctor, asked about what medications he was on, and he said that he was on these . . . he looked for the word. Finally he found it: steroids.

  “Those can mess with your emotions,” she said gently.

  He rubbed his left pectoral muscle and told us how hard it is to have someone care for him, alluding to his mother. “I hate to admit it, but I still need help. Every day is hard. I HATE my life.”

  He talked about how frustrating it was not to be able to think about the future. One of his great joys, he explained was coming up with ideas and creating things. “But I’m not allowed to do that. I just sit on the couch all day and watch TV and take an occasional walk. What if everything was taken away from you?”

  We changed the subject and reminisced about another day we had sat in the backyard—of his house in Boulder, right before the high school state championship game. Jason was ailing that day too, from a sprained ankle he had gotten when he leapt to block a shot. “I could jump,” he said.

  He became melancholy again. “I think how it would be easier for everyone if I was dead. But I don’t want to die! I want to be alive thirty more years.” And besides, this thing, this treatment, it just might take. “We’ll find out in two weeks. We may have a winner.”

  The treatment took.

  On October 5, he was back. I mean: BACK.

  “Dude, I’m so fucking psyched,” he told me on the phone.

  His blood sugar was in the normal range, he felt good, the cancer was in remission. Jason Greenstein, a man who just a few months ago had one foot in the grave, was spinning like a top.

  “I’m thinking about all these different businesses. I’ve had all these great ideas,” he told me. “The trinket box business is really good, but it doesn’t take up much time.”

  He began to focus on a specific idea: starting a new immunotherapy business with one of the doctors who was a consultant with Dr. Brunvand. Maybe he’d get into the drug business.

  “Dude,” Jason exalted, “Dr. Brunvand had told me that I had a one in twelve million chance of being alive. I’m not trying to beat the odds. I’ve beaten the odds!”

  At Thanksgiving, Cathy made a feast—turkey with stuffing, gravy, cranberry sauce, sweet potato soufflé, green beans, carrots and mushrooms, and pumpkin, pecan, and apple pies. Guy, Jason’s brother, made extra turkey. Cathy told everyone to come early. It would be a real celebration.

  “I’m so grateful. He’s alive and well. It’s a miracle!” Her voice rose in its high-pitched way. “I just wish Joel was here to see it.”

  It was just like old times, including the fighting. The Greensteins were birds of a feather, together, on Thanksgiving.

  Cathy and Jason, for instance, had been bickering because he hadn’t taken his cell phone to the camera store to print out the pictures of his medical journey. “That’s your documentation of what happened. If you lose the phone, you’ve lost it.”

  “Let it go, Ma. I said I’d do it!”

  “I just wish he’d focus on one thing,” she told me, then suddenly relented. “Well, he does feel still crummy some days.”

  The holidays came and went and Jason had good days and bad days. The cancer was gone, but years of ingesting piles of drugs, some he was still taking to deal with side effects, had left his body depleted. In February, he came down with a mild pneumonia and needed antibiotics. He was still on blood thinners, and his nose bled. One night he was at a restaurant called the Chop House and went to the bathroom to stop the bleeding. He accidentally dropped a bloody tissue on the floor and bent down to pick it up and his back went out. The shoulder blades and upper back just seized, and he could feel it in his stomach muscles and ribs too.

  Just a setback, he said. He’d already gotten a business plan written to do marketing and sales for an immunotherapy-related business with a doctor he was partnering with. “I’ve literally written and structured the business,” he said. “I’ve created the brand.”

  Snow pummeled Denver one mid-March day. Jason went to shovel his van out of the snow so that he could go to an appointment at the clinic. But he had broken his snow shovel in a frustrated painful fit a few days earlier, so he used a folding chair to clear a path out of the garage. He arrived to the clinic wet, cold, and two hours late. His back was killing him. He was X-rayed to check for worsening pneumonia or a bone lesion to explain the back pain. Nothing showed up, so it appeared the intense pain was most lik
ely due to shoveling the snow with the folding chair, maybe a muscle strain. At the end of his clinic visit, Dr. Brunvand drove him home. “I was certain his tires were bald and his van only had rear-wheel drive.” At his house, Jason gave Dr. Brunvand a trinket box that looked like a rose. “Chicks love this box; take it home to your wife so she will forgive you for being late,” he told his oncologist.

  Over the next few weeks, the back pain worsened. He kept shoveling the walk at his mom’s house in Denver, where he and Beth often stayed, but he continued to use the folding chair to do the shoveling. His back finally went out completely, leaving him in excruciating, immobilizing pain. He had the flu and some lingering pneumonia still. He went to the doctor and they scanned his spine. The cause of the pain wasn’t clear. Dr. Brunvand suspected the culprit might be a relapse of the cancer. At the base of Jason’s spine, they found what appeared to be a lesion. They weren’t sure. It looked like Hodgkin’s might be trying to sneak back in.

  I found out when I called Dr. Brunvand on April 7 just to check in. “He’s relapsed,” Dr. Brunvand told me.

  He favored using more nivolumab. It had saved President Carter from a melanoma relapse that had gotten into the spinal fluid. That showed the drug was capable of passing through the blood-brain barrier, so it might help Jason’s spine. More nivolumab for Jason also meant revving up the immune system, and that would risk more graft-versus-host disease. The chessboard was filled with land mines on nearly every square.

  “We’re in uncharted territory,” Dr. Brunvand told me. “I may sound like a coldhearted son of a gun, but freaking out and feeling sorry for ourselves is a luxury.”

  He described fighting cancer as a knife fight in which the disease keeps standing up again, attacking again. “You’re hosed if you lose your kind of thoughtfulness, your desire, intensity.”

  Jason, he said, had to fight back. Not everyone would agree, of course. Some people fairly reject such thinking as suggesting that Jason’s survival depended on toughness and tenacity, when cancer, as much as it is a knife fight, is also a game of chance. Sometimes you survive and sometimes you don’t, and your commitment to winning isn’t the difference between life and death.