In pursuit of a cure, when ideas and options have run out
A new book from Penn Medicine’s David Fajgenbaum chronicles his journey to beat Castleman disease, a rare disorder that he’s lived with for almost a decade.
David Fajgenbaum is an assistant professor of medicine at the Perelman School of Medicine at the University of Pennsylvania and associate director of patient impact in the Penn Orphan Disease Center. He also leads the Castleman Disease Research Program.
(Image: Courtesy of Penn Medicine)
This is an excerpt from David Fajgenbaum’s new book “Chasing My Cure” published in September 2019 by Ballantine Books, an imprint of Random House, a division of Penguin Random House LLC. Below, listen to audio of Fajgenbaum reading the excerpt.
It had been 15 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, semi-hurried 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 the University of Arkansas for Medical Sciences, 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: the protein Interleukin 6 (IL-6) was not the problem for all patients with idiopathic Multicentric Castleman disease (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 15 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 I had been given 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?”
I swallowed those final questions, but a hospital room is never 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 impossible to say.
It occurred to me, between the periodic beeps from my IV pole, that Dr. van Rhee was not saying “I don’t know” to my queries about my illness. He might have said, “I’m not sure, let me look that up…” and swiveled over to his computer to plug in the symptoms and dial up some answers. But he didn’t say that. He said, “No one knows.”
“Are there any other drugs in development or clinical trials?”
Dr. van Rhee was unfailingly calm and caring when he responded to my most important question. “No, not at the moment.”
“Are there any planned?”
“Not that I’m aware of.”
Dr. van Rhee was the undisputed worldwide expert on Castleman disease, and he didn’t know what initiated the disease or what caused it. Or how to prevent relapses in patients for whom the only experimental treatment in development didn’t work. That meant that no one knew. There were no more appeals. There was no higher bench. He was not flattering himself by speaking on behalf of the world’s knowledge of my condition. He was that knowledge. He didn’t just have authority; he was the authority.
As a medical student, I could select the correct answer to each of these questions for what seemed like every disease, but not this one.
“I know elevated Interleukin 6 is supposed to be the problem but blocking it hasn’t worked twice now and my Interleukin 6 tests were normal during my presentation and relapses. Is it possible that Interleukin 6 isn’t the problem for all cases?”
“It’s possible.”
That was it. It was possible. Anything was possible.
I knew what he meant. I knew the language that doctors use: the careful truth-telling, the hedging, the open-endedness. I’d spoken that language before. Now that it was directed at me, it didn’t feel nearly as careful or open-ended as I’d once assumed. Instead, the words felt like they were casting me out of the room, out of the hospital entirely. I’d been consigned to the plane of possibility. Anything was possible, because no one knew. I was on my own.
A proper patient might have taken Dr. van Rhee’s pronouncements with humility and acceptance, but ‘no one knows’ didn’t cut it for me. There are things we can change and things we cannot change. We need either the grace to accept them, the ignorance to not know the difference, or prayers to find another expert who has the answers. I am not graceful. I was no longer ignorant of the realities of iMCD. And I was getting tired of praying.
A whole mental structure built on faith and expectation—or hubris—collapsed for me that day. When Dr. van Rhee entered that room to discuss my disease rationally—doctor to emerging doctor—I had believed there had been a vast, unseen, but highly coordinated system of scientists, companies, and physicians working diligently to cure my disease. Every disease, actually. Of course there was—right?
Like Santa and his elves working to grant wishes to every good boy and girl in the world, I imagined that for every problem in the world, a highly qualified team worked diligently, perhaps in a workshop, and it operated out of sight, out of mind, right up until the moment that it solved the problem. Right on schedule, deposited in your living room, and wrapped in a bow, the problem is solved, revealing the magic of the workshop’s efforts. Google reinforces this belief.
For every question you can think of, Google provides an answer—and often data to back it up—with a speed and precision that inspire confidence, if not always comfort. The frequent news about medical breakthroughs feeds this optimistic illusion: You assume that someone, somewhere has already figured out the answer to every medical question you could ever pose or, if not, that a team is hard at work solving your particular puzzle to meet your particular medical need as quickly as possible. A cure is near; discoveries will happen whether or not you contribute time, talent, or dollars toward them. So, I had waited on the sidelines because I believed others were on the case. But now that illusion was no longer possible to sustain. Not when Santa Claus himself was looking me in the eyes and telling me nothing would materialize, gift-wrapped, to cure me.
Nausea overwhelmed me, partly because of the chemotherapy cocktail that had been slowly dripping into my veins during our conversation, and partly because of the realization that I was completely alone. I was terrified. This was the fourth time in the past two years that I would approach the precipice of death. This time, I knew that I would die because the only drug in development for my disease had failed to work. The harsh reality was that the medical community didn’t understand the most basic aspects of my illness—the only thing the medical community “knew” to be true was actually wrong—and the world’s expert in it had run out of ideas and options.
Despite the fact that my immune system was consuming all of my energy as it attacked my organs, despite the accumulated toxins and chemotherapy that made my thinking cloudy, I had the most clear and important thought of my young life: I could no longer just hope that my treatment would work. I could no longer rely on the previous research. I could no longer hope someone else, somewhere would perform research that would lead to breakthroughs that could save my life. If I were to survive again—and to survive long term—I had to get off the sidelines and act. If I didn’t start fighting back to cure this disease, no one else would and I would soon die. I would never get to marry Caitlin or have a family with her.
Dr. van Rhee was the foremost expert in the world on Castleman disease—Santa himself—but the foremost expert in the world can only ever know as much as the accumulated knowledge in the world. If the answers have not yet been uncovered, then the foremost expert couldn’t possibly know them. These answers weren’t Google-able, and prayers couldn’t help to find the doctor who knew them. No one knew. Even worse, there were no promising leads being chased. The limits of Dr. van Rhee’s potency were the limits of the world. They were also now my limits, and other patients’ limits, too.
My body was dying. I was in overtime. I was spent. But at least I wasn’t on the sidelines anymore. Now I was in the game, and I knew what I had to do. I would simply have to increase the world’s knowledge of iMCD.
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