Chasing My Cure

by David Fajgenbaum

  But here again there are big systemic barriers that stand in the way of using off-label drugs to advance science and patient care: The uses and effectiveness of these treatments are rarely tracked or aggregated, so future physicians are not able to build upon the results of previous treatment attempts to make future care decisions. Thus, some patients are started on a treatment that had never worked before while other patients are never started on an off-label treatment that is almost guaranteed to work, because of a lack of data. This is particularly painful and paradoxical in a time when so much data are being generated. The more I looked into the realities behind some rare diseases, the more the situation seemed to resemble the dysfunctional organization of intelligence and police forces before 9/11—everyone was doing their best job individually, but no one talked to one another, no prime database existed, there was no expectation of coordination or data sharing.

  My crash course on the world of orphan diseases did reveal some bright spots and brilliant leaders. One such leader was Dr. Dan Rader, a distinguished physician-scientist at the University of Pennsylvania whom I first met through the Orphan Disease Center. He had recently conducted research that suggested that a drug sitting on a shelf at a major pharmaceutical company might be effective for patients with a deadly genetic disease called homozygous familial hypercholesterolemia. It was not being used because the side effect profile was too severe to try it in the general population. But the genetic condition was causing children and adolescents to die, and Dan thought this drug might work for them. He knew his patients (and their parents) would be willing to deal with the side effects if the drug could extend their lives. Dan worked with the drug company to study its efficacy. Sure enough, the trial was successful and resulted in an FDA approval. A drug sitting on the sidelines, waiting to save lives, had been neglected until the right person asked the right questions. How many more of these drugs were out there waiting to be deployed for the right disease?

  Was there one for Castleman disease?

  And how many drugs are already FDA-approved to treat one disease that are also effective at treating another disease and possibly many more? This was a line of questioning that I would never again put down. I became consumed with the idea that many of the answers we sought were already available. They’d just been forgotten, ignored, or not yet connected to the right questions. Kind of like a game of Jeopardy! but with really high stakes.

  The bottom line I took from my work with Arthur and the Orphan Disease Center team was that organization mattered. I’d seen dysfunctional teams before. I’d even contributed to some. But I also knew what a singularly focused leader could do, as a point of connection around which a team can unite. I was never the fastest runner or farthest thrower, but I was a good quarterback. Each rare disease needs one.

  Another rare disease quarterback that I met around this time was Josh Sommer. He had dropped out of Duke a few years before when he was diagnosed with chordoma—a rare bone cancer that often appears in the skull and spine—to create the Chordoma Foundation. He didn’t create just any old foundation that directs funds for research. He created a force for change, invested in the creation of publicly available resources, and connected researchers around the world. His leadership has led to research breakthroughs and multiple promising clinical trials. As I listened to his story in a crowded and noisy coffee shop, I thought: Should I be doing this for Castleman disease?

  Then, Josh interrupted my thoughts: “David,” he said, “you’re uniquely qualified to make an impact. It may not be my place to say this, but Castleman disease needs you.”

  I spent the next few days convincing myself that my time and energy should be focused on growing AMF and becoming an oncologist. I felt sure that others were on the case: Castleman disease already had two dedicated foundations, the International Castleman Disease Organization and Castleman’s Awareness & Research Effort. I assumed they were both pushing research forward as quickly as possible. I decided to remain on the sidelines, hoping and praying that some researcher somewhere would figure out my disease. But a seed of an idea had been planted.

  * * *

  —

  Medical school meant more clinical rotations. Pediatrics. Internal medicine. Family medicine. Interventional radiology. Emergency medicine. Rheumatology. On each rotation, I saw doctors and residents daily who had treated me when I was so sick. I didn’t remember most of them, but they remembered me. Every time I’d pass them, they’d say, “David, you look so great!” I think this was quite confusing to the other physicians I was working with, who had no idea I was ever sick. “You look great” isn’t typically how physicians greet one another in the hospital.

  My free time during the week was spent working on the Orphan Disease Center and the weekends with Caitlin. I let myself believe that I was healthy. That the previous months of hell had been a deviation from what would be my normal, contented life.

  Though I stayed away from conducting Castleman disease research, I did end up writing a case report on a Castleman disease patient (me). I wanted to highlight how the eruption of those blood moles or cherry hemangiomas could be a sign that someone may have iMCD or will soon have a relapse, which had happened to me each time. The journal JAMA Dermatology published the case report and put a photograph of the blood moles on my bare chest on the cover. That was a first—I was a cover model!

  I hoped that awareness of these blood moles would help to diagnose other patients more quickly, detect relapses earlier, and serve as a piece for solving the puzzle of this mysterious disease. And I secretly hoped the doctors who had scolded me to “forget the blood moles” would receive copies.

  I was thinking and then doing.

  And I was beginning to breathe easy.

  But I already had a second Red Bull today.

  And I got enough sleep last night.

  I have too much to do.

  Why am I so tired?

  Why?

  * * *

  —

  I was on a rotation in Pennsylvania Hospital when it started again in April 2012. I was listening to a patient tell me how he was feeling after knee surgery when suddenly the fatigue that I’d been fighting all day crystallized into a familiar feeling. I watched the man’s lips move. The sounds from the room faded away. So much was going through my head. I excused myself and rushed to a room where I often studied between seeing patients. It was a part of the original hospital. During peaceful moments in the past, I’d imagined that Ben Franklin, who’d founded the hospital back in 1751, could have been in this same room many times. Maybe he’d come here for some privacy, just as I did. Taken off his wig and kicked back.

  But medical history wasn’t on my mind today. I needed a nap, and I needed to tamp down my mounting anxiety. I shut the door, balled up my white coat into a makeshift pillow, set my alarm for seven minutes later, and lay down on the floor. Just as I closed my eyes, I calmed myself with a reminder: You’re getting siltuximab every three weeks. It’s the drug. It targets the problem in this disease. There’s no way you’re relapsing. You’re just tired. You’re just tired.

  That night, I literally and figuratively sat on my hands and considered whether I should feel my neck for enlarged lymph nodes. This line of thought was totally irrational—I didn’t have anything at all to gain by not knowing, and reaching up to palpate my own neck was something I wouldn’t be able to avoid long term. But I knew mine was a common enough attitude. Every doctor has encountered patients who waited too long, even when they suspected that something was wrong, to seek help. They didn’t want to know. I’d often been frustrated with these people. Now I understood.

  Needing to know won out, and I found exactly what I didn’t want to. Bulges along both sides of my neck. But a lot of things can cause enlarged lymph nodes, I thought. Which was true. True enough to warrant inaction for the night.

  The next morning, however, I emailed my
doctors to confess that I had not done the PET/CT scan they had recommended I do in January, a test that would detect new disease activity. I explained that with all of my responsibilities for the Orphan Disease Center and medical school rotations, I hadn’t wanted to give up an entire morning to the scan process. But now—three months after I should have had the follow-up scan, which could have detected early signs of disease activity—I had new symptoms. I was told to get to the scanner the very next day.

  When I spoke to Caitlin that night, I told her about my day and we planned our next visit. But I didn’t mention the new symptoms. I didn’t want her to worry. It was probably nothing. I was holding back on the transparency and vulnerability I had committed to give her, but, I reasoned, no one wants to hear about every ache and pain, and until I knew that this wasn’t just a cold or the flu, she didn’t need to go down the rabbit hole of worry with me. With the benefit of hindsight, I can see now: I was that afraid.

  That night I woke up in a cold sweat; the sheets were completely soaked. When I got up to change them, I saw the last piece of evidence I needed: The blood moles were back, all over my torso.

  I permitted myself one more cycle of magical thinking: I couldn’t be relapsing, because I was taking siltuximab. Siltuximab would prevent relapses, as Dr. van Rhee had said. Full stop. I was healthy.

  Everything was fine. It had to be. I knew that my disease couldn’t come back while I was on this experimental drug. I’d gotten my miracle. The kind of miracle my mother hadn’t had for her cancer, and so many others don’t get for their diseases either. If siltuximab actually couldn’t stop my disease or prevent relapses…

  My patient-self retreated somewhere dark. My diagnostician-self took the tiller.

  I pulled up my PET/CT results on my phone the next day as I walked to a patient’s room. The scan indicated that my lymph nodes were as large as they had been when I was hospitalized the first time around and they had increased metabolic activity. This should have indicated a relapse and prompted immediate blood work and a dose of siltuximab. I would have recommended exactly that course had I been my own patient. But I was still my old, stubborn self: I explained to my doctors that I needed to complete the clinical rotation I was on, and besides, I had a lot to do to prepare for AMF’s annual fundraising gala, which was on Friday in Raleigh. And actually, then we had an important AMF board meeting on Monday, so the blood work and dose of siltuximab would have to occur on Tuesday. And I then explained it the same way to Caitlin. I downplayed the significance of the needed blood work to her just as much as I did to myself. She was concerned but comforted by the explanations—or rationalizations—that I had for everything that was happening.

  Don’t worry, I thought and said. It can’t be a relapse.

  Unfortunately, my doctors trusted my judgment, and I didn’t get blood work until a week after I’d felt my enlarged lymph nodes. Several test results were abnormal. The most important one we were monitoring was C-reactive protein (CRP), a marker of inflammation and immune system activation. During my three previous flare-ups, it was my most reliable disease marker, spiking when I worsened, rising above 300 at my sickest, and improving when I felt better. It was the test, and it had remained normal for the last year.

  The number did come back elevated, but only slightly, to 12.7. The normal range was 0 to 10. What’s 2.7 points above normal when you’ve touched 300? It was an enormous relief. I got back to thinking that I was overreacting, that I was only feeling a little sick with a garden-variety virus, just like anyone else. After all, I’d had a sore throat. Maybe the sore throat could explain why my CRP was mildly elevated? Based on my enlarged and newly active lymph nodes, my doctors decided to administer a dose of siltuximab a week earlier than the usual spacing. Just to be safe.

  As during all of my previous infusions, my sister Gena sat next to me and I worked on my computer with complete focus on whatever AMF emails or Orphan Disease Center documents I was working on. Today is just like any other day, I kept telling myself. I decided to stay in Raleigh and repeat blood work in two days. Just to be safe.

  Two days later, my CRP had shot up to 227. This was shocking above and beyond its indication that I was truly relapsing; a spike from 12.7 to 227 so quickly was almost unthinkable. So my doctor and I did what every good practitioner should when he or she gets a weird number: recheck the result.

  It appeared correct—until we looked back at the previous report and realized that the CRP level was measured in different units at the different hospitals. The 12.7 reading was a measurement in milligrams per deciliter, not milligrams per liter, as we were used to. That meant that our decimal point was in the wrong spot. Tuesday’s CRP level had actually been 127.

  We should have already been panicking.

  Not only was my iMCD coming back, but its intensity had doubled in just two days, even after I’d been given the drug that was supposed to treat it. It felt like Castleman disease was taunting me, toying with me, showing just how much more powerful it was than the treatment into which I had channeled all of my hope.

  Since our new weapon had failed, my doctors reverted to an old trick: I was immediately given a dose of the chemotherapy that had worked for my second flare (even though it didn’t work for my third one). We were now fully grasping at straws.

  I gathered myself, and I called Caitlin. No more rationalizing what was happening. It’s not some strange cold. It’s back, I admitted. I knew that she had decided to be with me fully cognizant that I still had the disease in me and that it could come back at any time, but I couldn’t not feel like this was somehow a betrayal. I hated that I had to “test” her so quickly. I hated that she had to think of these things at all. She was still living in New York, but she made arrangements to meet me in Philadelphia before my father and I would fly to Little Rock; she would come to Arkansas a bit later with my sisters. This would be her first time seeing me battle iMCD. She couldn’t get into Philadelphia until that evening, so I went to see each of my closest med school friends over the course of the day. This routine of saying goodbye was something I’d done before.

  By the time Caitlin arrived, I’d pulled myself together and was projecting positivity. It was true that I was relapsing yet again, but there was something almost comforting in the serial nature of my disease course: I’d gotten sick three times before, yes, but I also hadn’t died three times! I had an amazing doctor, who was very good at keeping me alive. And he must have tons of new tricks up his sleeve after the last year of work by Santa’s helpers.

  It had been fifteen months since I was in this hospital. Not much had changed in Little Rock, at least at the hospital. It was still the center of the Castleman disease world, still bursting with hope in various forms. Overeager smiles, firm handshakes, clipped green lawns, and that same brick-and-glass hospital architecture that connoted quick, semihurried service the world over.

  I was different, though. I had the collective wisdom of the past year plus in my pocket. I had the private potency of think it, do it in mind. I had gotten plenty of chemotherapy in the past. I felt like I could handle anything.

  I was also overconfident. The results of new blood tests in Little Rock came back far worse than they had been in Raleigh. Castleman disease was back and it was roaring. Within a couple days of arriving at UAMS, my liver, kidneys, bone marrow, heart, and lung functions were all deteriorating. I’d seen these lab abnormalities before in myself and my patients. I’d dealt with bad results and bad news. But never had a series of lab tests brought so much disappointment and such a definitive implication. I kept returning to the horrible disappointment that all this was happening while I was on treatment with siltuximab.

  My relapse meant one of two things:

  I actually somehow hadn’t received siltuximab due to a mistake, or I had received the wrong dose of siltuximab. (I rated this unlikely.)

  The only drug in
development for my disease wasn’t working, and I had no other options. This also would mean that the medical community was wrong: IL-6 was not the problem for all patients with iMCD, so siltuximab would not help everyone with my disease. (I rated this as likely.)

  These two possibilities were quickly whittled down to one: Detailed hospital auditing records confirmed that I had received siltuximab at the appropriate dose for the previous fifteen months. Everything had gone as it should have, and I had gotten very sick anyway.

  We were back to square one. The only thing the medical community “knew” about iMCD was not correct for me. Interleukin 6 was not the problem for everyone with iMCD. Siltuximab wouldn’t work for everyone, including me.

  The siltuximab that I had been on for the previous year and the single dose of chemotherapy I had received a few days before in Raleigh were clearly not slowing things down, so Dr. van Rhee decided to take the “shock and awe” approach again. I was immediately started on the same combination of seven chemotherapies as before. Like before, the cocktail targeted my immune cells and other rapidly dividing cells like my bone marrow, hair, and intestines.

  I needed answers. I may or may not have been approaching death for the fourth time. As the chemo cocktail dripped into my arm through the IV pole at my side, I asked Dr. van Rhee everything I had been obsessing over since I started to feel sick again.

  “What causes this to happen?”

  “No one knows.”

  “Which type of immune cell is responsible for initiating this?”

  “No one knows.”

  Why not? I wanted to ask.

  And why me?

  I swallowed those final questions, but a hospital room is never, ever silent, even in the dead of night, or even when a conversation grinds to a halt and the participants are left to quietly pick at the implications of what’s been said, and what’s been impossible to say.