Chasing My Cure

by David Fajgenbaum

  It worked. Had her life not been saved by tocilizumab, the entire CAR T cell research program may have been shut down. Today, CAR T cell therapies are FDA-approved for treating multiple types of leukemia and lymphoma and are the latest hope in the moon shot fight against many other cancers too.

  There’s a sense in the public that these so-called miracle drugs are popping up every day and that the medical field has the answers to nearly everything that ails us. Much of this sense comes from the fact that we hear about only the “breakthroughs” in the media. Headlines don’t say, “One hundred thousand laboratory experiments did not result in a single breakthrough today.” Many believe that these “miracles” just happen, and they fall into the researchers’ laps. That’s certainly not true. Tocilizumab is a case in point. Dr. Kazuyuki Yoshizaki, who first discovered elevated IL-6 in a few iMCD patients and spent more than a decade developing tocilizumab for the treatment of iMCD back in the 1990s and 2000s, tried it on himself before administering it to any other humans in an experimental clinical trial. He wanted to prove it was safe. When I asked him about it, he laughed, pointed to his arm, and said, “No, no, no. I didn’t administer it to myself. The nurse, she administered it to me.”

  Kazu isn’t the first medical researcher to experiment on himself, or the last. In fact, twelve Nobel Prizes have been given to self-experimenters. Dr. Werner Forssmann pioneered the development of cardiac catheterization by first inserting such a catheter into a vein in his arm and successfully guiding it to his heart. Dr. Barry Marshall proved that a particular strain of bacteria causes ulcers by drinking a broth filled with the bacteria. This led to a Nobel Prize and also an entirely new way of treating—and curing—such ulcers.

  Kazu’s example—that of both scientist and subject—would come to be very, very significant for me.

  As I researched Castleman disease, I felt a part of me reemerging, a part I had had to lay down when I first dragged myself into the ER: I felt like a doctor again. Some of that identity no longer wore as well as it once did. As a doctor, I had been trained to look at disease as the sum of the parts that fit into our diagnostic tools. We were trained, rightly, to attend to what we could fix, and what we could fix only. When I became a patient, the deficiencies of this straitened approach revealed themselves to me. I began to understand what Susan Sontag meant when she said that each of us is born with dual citizenship, ultimately obliged to spend some time in the Kingdom of the Sick. My disease wasn’t just the sum of its symptoms; it became a relationship I had to the world, and to the people around me.

  I was very much a citizen of that kingdom one day in North Carolina, seven days before we were scheduled to leave for Arkansas, when my sister Lisa patiently helped me go to the mall to walk some laps. There were no other “walkers” that I could see; the place was packed with Christmas shoppers. I had been discharged from Duke a couple weeks earlier, and I was in a good stretch, eager to improve my fitness. I was sporting one of my new XXXL gray sweat suits to try to cover my distended belly, still full of about five liters of fluid, and my feet were too swollen to fit into any shoes, so I wore hospital socks and Adidas sandals with the Velcro straps adjusted to maximum width.

  I looked like I had just escaped from Nurse Ratched. But I didn’t care. I felt great.

  I rounded a corner and briefly made eye contact with a woman about my age. I smiled and had reason to hope for a smile in return. In case you’ve never spent time in the South, let me tell you that it’s a truth undiminished by cliché: People smile back. But this woman not only didn’t smile, she gave me a look of absolute revulsion. Lisa caught the brief exchange, and she and I burst into laughter. For a brief moment I had forgotten that I was in the kingdom…And to laugh felt so good. I guess I no longer looked like the Beast of before, but more like I’d been attacked by one.

  * * *

  —

  Our family celebrated Christmas together, and it felt even more special than it had in all of the years since my mom had died. But I still couldn’t get my mind off what I really wanted from Santa: for Dr. van Rhee to give me my health back.

  When we finally arrived in Little Rock the next day, we got into a shuttle at the airport and said we were going to the University of Arkansas for Medical Sciences. The driver asked, “Is it for Castleman disease?”

  I was completely shocked. “Yes.”

  “I thought you looked like you might be a Castleman disease patient.”

  It had taken doctors at top medical centers eleven weeks to figure out I had Castleman disease, but the shuttle driver got it at hello.

  “Well, you’re in the right place. Dr. van Rhee takes care of Castleman disease patients from around the world.”

  This was comforting. For the first time, I was going to a place where what I had was normal.

  The same thing happened when we checked in to our hotel and when we walked into the clinic. Everyone we met seemed to know about Castleman disease. I had just been at a top medical center where specialist physicians didn’t know anything about Castleman disease and the top medical resource in the world erroneously said there was only one patient reported to be alive with my subtype. I could definitely say, now, that this wasn’t true, since there was a line of iMCD patients waiting to see Dr. van Rhee that morning. I was finally in the right place.

  I’d come prepared. Like all good obsessives, I’d put together a PowerPoint to track my initial differential diagnosis as well as symptoms and lab tests for the last few months. The report had ballooned to over one hundred pages, and when I shared it with Dr. van Rhee I was nervous he might roll his eyes and look at his watch—here I was, a patient, a medical student, supposing to educate the master. But that wasn’t his approach at all. Instead, he spent three hours with my dad and me to review the data and come up with a detailed treatment plan. As we talked, we discovered that we had more than an interest in Castleman disease in common: His wife is from Trinidad and grew up in the same neighborhood as my mom. We reminisced about the island, our favorite Trini foods, and our favorite beaches.

  Those shared cultural touch points were comforting, but the most encouraging part was that what he was proposing represented the sum total of the world’s knowledge on my illness. It—and he—was amazing. He informed us that a pharmaceutical company was studying a drug called siltuximab, which blocked IL-6 directly, as a treatment for iMCD,* and it was already in Phase II of clinical trials—the first Phase II, randomized controlled study of iMCD ever. If it was successful, the FDA would likely approve siltuximab for use in iMCD. Early reports were really encouraging. I was shocked to learn that the clinical trial was enrolling patients just fifteen minutes down the road from Duke, at the University of North Carolina, and neither I nor my doctors had been aware of it when I was dying there. My own IL-6 levels had not been elevated when they were tested during my initial presentation and relapse, but Dr. van Rhee explained that, based on what’s known about iMCD, I must have elevated IL-6—it’s a critical component of iMCD. He went on that the test for IL-6 is not very good, so it was likely falsely low. Our plan was for me to return to North Carolina to enroll in the siltuximab clinical trial. It was the only drug in clinical trials for iMCD and it directly targeted a critical factor in the disease. This, finally, was what I’d been hoping for. Expertise, plans, and action. I was elated.

  At the end of our appointment, Dr. van Rhee walked me down the hall to meet another patient, a man about my age with iMCD who’d also spent months in critical condition in an ICU and then nearly died again when he relapsed. He had experienced multiple strokes and had a large portion of his colon resected and was now nearly back to 100 percent thanks to the same experimental drug that Dr. van Rhee had recommended for me. He put a face on my future, and it made me more hopeful than I had been in months. I was going back home, but this time I was armed and dangerous. No more passive hope.

  That was the plan, at least. We
got in a cab the following day to go to the airport. Between the moment we stepped into the cab and the moment we stepped out, I realized I was relapsing. The fatigue and nausea had been worsening over the previous couple of days, but between my visit with Dr. van Rhee and finally having a plan, I avoided connecting the dots. Then it started hitting me hard. At the airport, to confirm my hunch, I pulled up a website with the results of blood tests performed at van Rhee’s clinic. There was no question. My body and my blood told me everything.

  Round three was starting.

  We left the terminal, got back in a cab, and returned to the hospital. I was disappointed and scared. But, hey, at least I was in the Mecca for Castleman disease, I thought to myself.

  Dr. van Rhee immediately admitted me and started me on higher doses of the same corticosteroids that had saved my life at Rex and a double dose of the chemotherapy that had saved my life at Duke.

  Within a few days, it was clear that they would not be effective this time around. My Castleman disease was roaring.

  I was quickly started on dialysis to replace the function of my failing kidneys. I received multiple blood, platelet, and albumin transfusions, every day. They pulled six to seven liters of fluid out of my abdomen a few times a week. My body became a site of coming and going, taking and leaving, stopping and starting, and failing.

  The clinical trial that Dr. van Rhee wanted me to enroll in required an eight-week period without any other treatments before starting. That way you know that any observed improvements are due to the siltuximab. My doctors and I knew that I couldn’t survive that long without treatment, so Dr. van Rhee appealed to the FDA and the drug company for emergency compassionate use to allow me to receive the experimental treatment even though I couldn’t enroll in the formal clinical trial. Considering my grave illness and lack of options, they granted the request.

  I received the first dose and hoped. During my infusion, a clinical trial coordinator told my dad and me about how she had seen patients experience dramatic turnarounds within just a couple of days. She and my nurse explained that if my IL-6 level began to rise very high after siltuximab was given, that would be a sign that the drug was going to work for me.

  Two days went by and my condition continued to worsen.

  I felt no improvement, and my lab tests confirmed that things were getting worse.

  My organs continued to fail.

  And then finally the sign that we’d all been hoping for! The level of IL-6 in my blood was now more than one hundred times greater than normal. My nurse and trial coordinator reminded me that this indicated that the siltuximab should start working soon.

  So my dad and I celebrated with a high five, and he called family and friends to share the news. Then, we waited for my miraculous turnaround to occur.

  Two more days passed. My organ function deteriorated even further, and I began to lose consciousness again. One of my doctors informed me that we couldn’t wait any longer for the drug to work. I was approaching the point of no return.

  The miracle drug had come. It targeted the one thing “known” about the disease: IL-6 was the problem, and yet blocking it hadn’t worked. No other drugs were being studied.

  Though my thoughts were foggy—my brain was also suffering from the multiple system organ failure—I was still provoked by the intellectual problem: Why hadn’t blocking IL-6 worked the way we’d all expected? What was different about me? I understood that it was unlikely I was going to live long enough to ever know the answers to those questions.

  Dr. van Rhee came by my room to discuss what to do next. During our brief chat, we both reasoned that maybe the siltuximab was actually working and that I would be even more sick without it or maybe it was just going to take more time than we had for it to start working. After he left, I thought to myself that perhaps my samples would be useful to Dr. van Rhee’s research in the future and to future patients like me. But there in the hospital, the pressing matter wasn’t research. It was keeping me from flatlining. There was nothing left to do but fight fire with fire.

  Dr. van Rhee decided to initiate the closest thing to a “shock and awe” campaign on my disease—a combination of massive, obliterating doses of seven chemotherapy drugs that is known by the initials of its ingredients: Velcade, dexamethasone, thalidomide, Adriamycin, cyclophosphamide, etoposide, and rituximab. The worst components of VDT-ACER would be deployed continuously for the first four days. Then, agents targeted at specific and strategic aspects of the immune system would be administered every couple of days for the next seventeen. The regimen was originally developed to treat multiple myeloma, a blood cancer with similarities to iMCD, and had never actually been studied in iMCD. The team dutifully warned me about the side effects that I’d endure, but I told them to bring it on. I knew what to expect, at least by the book. The toxicity was off the charts. They said my hair would fall out, they said I would be constantly vomiting, and they said this might prevent me from being able to have children.

  My hair fell out. I vomited, frequently. I wasn’t ready to give up on the possibility of children in my future, but I needed to survive this if I was going to have a chance. My father sat by my bed and encouraged me to eat crackers.

  The obscene thing was: I felt better with every new dose of chemotherapy. The iMCD flare-ups were so all-consumingly awful that the semicontrolled poisoning of VDT-ACER was an improvement. My brain was still cloudy, and moving most of my body still wasn’t possible. But every step in the right direction felt amazing even if it was gradual. I was benefiting from one of the greatest of all aspects of human psychology: habituation. Anything felt better after escaping from hell.

  The drugs were killing my immune system, which had been trying to kill me. It was a temporary fix, but that’s all I could expect until someone could crack the iMCD code.

  In the meantime, I had a new appreciation for the drugs that I’d spent my whole medical education learning about. They’d always just been tools in the tool kit of the physician. But now I got it: Drugs save lives. Doctors administer them.

  Don’t mistake me—I think doctors are the catalytic element, but drugs are the underlying material. This will piss off some doctors, I know. I would have been pissed off by this thinking back before my own journey. In the medical community, there is often a resistance to acknowledging the primacy of drugs and I think that this resistance can sow confusion. In a very real way, the drugs available to us represent the hard limits of what we can do for patients. Of course, when to use and when not to use a treatment is a highly complex decision and requires the special insight of a great doctor, but you can’t target something if a drug doesn’t exist to target it.

  Whether it was a side effect of all those wonderful drugs, or just the need to unburden myself after coming back from near death for a third time, I strangely felt the urge to confess to my dad about each of the times that I had lied to him while I was growing up. It was now about six months since I first became sick, and he had been sleeping in a pullout chair, by my side, every night. Maybe I felt like he deserved hearing the truth after all he had done for me. Maybe I felt like I needed to get everything off my chest in case I took a turn for the worst; maybe I figured I was still in such bad shape he wouldn’t get mad at me about anything. Whatever triggered it, I confessed to a lot of “borrowing” the car when he was out of town and ignoring sensible advice. He forgave me.

  He also gave me privacy so I could call Caitlin from my room. Once again, she and I began to reconnect, filling each other in on the details of our day-to-day lives. I infused all of my energy into what became weekly calls. Though my updates for her were decidedly less upbeat, I loved hearing about even the mundane details of her life at work. She had taken a job in New York in the fashion industry after college, and it made us both laugh to think that anyone could consider an incorrect stitch or unexpected shade of green to be a life-or-death mistake. We knew better!


  On New Year’s Eve, I felt well enough to walk laps around the hematology/oncology floor with my dad by my side. I had a belly that protruded about as far as my now eight-months-pregnant sister’s, and I wore a mask to limit my risk of developing an infection, since my immune system was weakened—intentionally and fortunately—from all that chemotherapy. As we rounded a corner near the family waiting area, we noticed a man who showed every sign of having been drinking that evening. It was New Year’s Eve after all. On our next lap, we saw that he had fallen out of his chair and was lying on the floor. My dad, ever the doctor, rushed over to help him back up. The man slurred out his thanks and then added, “Good luck to you and your wife.” We continued on, confused, until I looked down and realized that due to my protruding belly (and, I hope, the man’s intoxication), I must have looked like I was nine months pregnant and we were walking laps to speed our delivery. He thought I was my dad’s pregnant wife! I couldn’t resist telling my dad: “Man, you’ve got an ugly wife.” We were soon doubled over with laughter.

  Death isn’t funny, of course. But I came to understand that in no situation other than facing death is a sense of humor more necessary.

  It could have been bleak as hell to be so grotesquely twisted and transformed by my organ failures that I was misgendered by a drunk. That could easily be rock bottom in a different story, told by a different person. It might well have been rock bottom for me before I got repeatedly sick. After all, I was once full of pride and competitive spirit, and capable of 375-pound bench presses; I won’t pretend that I never cared about how I looked.

  And not that much time had passed since very similar conditions had made me act very differently. I wasn’t laughing when I turned Caitlin away because of fear that my appearance would be burned into her memory. That wasn’t funny. It won’t ever be.