Chasing My Cure

by David Fajgenbaum

  I knew what that meant. My father is not a sentimental man. He wasn’t going to play a love song. To put it politely, he has a colorful sense of humor. The saving grace was the thickness of his Caribbean accent. Except for the twenty-four Trinidadians in attendance, none of the guests could make out the inappropriate lyrics of the songs he sang. I was about ready to jump up and start pulling plugs, but I stopped myself. We were in a ballroom that was just about a mile down the road from the ICU in Philadelphia where my dad and I had shared a room when I first became sick. I remembered him staying with me, pestering doctors, keeping notes, calling in favors…and he never left my side for relapse after relapse after relapse after relapse. I realized that he deserved this. I wasn’t the only one who’d been through the wringer. My family had too. I was getting married; my dad deserved his moment in the spotlight. And, right on cue, he used that moment to sing the songs about the “man with the big bamboo” and the “honeymoonin’ couple” who were fighting about who should be “on top” (of the suitcase they were trying to close). At least my Trini relatives were laughing.

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  In the lead-up to the wedding, I had not taken my foot off the proverbial gas on my Castleman disease research. I wasn’t going to make the mistake of throttling down because I’d found a treatment that might be promising. After the wedding, though, the CDCN team really started to take shape. I began to recruit colleagues in earnest, and for the first time I was including my story as part of the CDCN story. I was breaking my silence as a patient with the disease that, before, I had been presenting as solely a professional interest.

  It may sound minor, but this shift felt momentous. I started to talk in public about my diagnosis and what I’d been through. I went back to business school in the fall, and I no longer tried to hide my health from my classmates and colleagues. No more secrets. It was no longer important to me to present myself as two different people—the “serious” physician-scientist–MBA student who went to school, studied medicine, led the CDCN, and conducted research, and the sick me. I was both things at once, and from that point on, I knew I always would be.

  My newfound openness engendered many offers of help, which I gladly accepted. I started to assemble a sort of Castleman commando team—the kind you see in movies, made up of a surprisingly motley and complementary group of people.

  The main difference between us and real commandos, however, was that we had no money. Castleman disease isn’t just incurable, it’s underfunded. Business school made me realize that I had neglected this side of the equation, and it was severely limiting our potential. Our organization couldn’t just be a few medical school friends, patients, and loved ones working on nights and weekends with an annual budget of $15,000. Other diseases with similar incidence, like ALS and cystic fibrosis, had multiple orders of magnitude more research funding: More than $50 million of public and private funds go toward ALS research every year; $80 million for cystic fibrosis. And those diseases deserve and need more too! If it hadn’t been clear to me before, it was now: We couldn’t do it on our own, not at one-fiftieth of 1 percent of the funding for similar rare diseases. If we really wanted to turn the tide against Castleman disease, we needed to expand our effort to include more than just those directly affected by it. More people needed to learn about it, so it wouldn’t continue to be one of the most deadly, most common diseases that most people have never heard of. We needed to start a movement to raise more funds for our research from the general public, and we needed more manpower to execute our ambitious research agenda.

  One of the first commandos was a business school classmate named Steven Hendricks, a six-foot-seven former NASA engineer and a wizard at turning our esoteric medical jargon into public-ready words that told our story and broadened our reach. He took on our website relaunch and built a new online patient community. He was also excellent at telling me I was wrong. I needed that. My background still made me research-oriented—I always wanted to go over results, find new leads, and pursue those leads above all else—but Steven would tell me, “No, Dave, it can’t all be about the research.” He was right. Medicine in the twenty-first century isn’t a separate, celestial pursuit, carried out in laboratories and libraries. Medicine isn’t just science; it’s advocacy too. The possibility of healing depends on the ability of men and women to marshal efforts toward that healing. It depends on money, and it depends on storytelling. Steven helped me realize that. He also loved to make the point that biomedical research was just begging to be revolutionized and accelerated with nascent technologies and disruptive approaches, just as so many other industries had been in the past few years. He would go on to say that our approach to transforming biomedical research for Castleman disease “wasn’t rocket science” and our repeatable steps needed to be spread to other diseases. He was the only person I’d ever met who could actually compare things to rocket science and know exactly what he was talking about.

  Another business school classmate, Sean Craig, who was a former Army officer, West Point grad, and project manager at Exxon, came into the CDCN with one mission: to infuse order and structure. He built new planning documents to track our progress virtually and to strengthen our organizational infrastructure; he effectively split our volunteer team members into multiple divisions. He was exactly what our rabble needed. And almost best of all, despite his Beast-like exterior and pedigree, he too shared an appreciation for Borat. Game recognizes game.

  Barclay Nihill, a business school classmate and former private equity investor, would evaluate our projects in terms of “investments”—of time, talent, and treasure—and pushed us to work in ways that could be quantitatively measured. He wanted us to be able to convince numbers wonks like him of our value and impact. He was also classically scrappy—physically one of the smallest among us, but he would have done anything for our team.

  Sheila Pierson, a four-foot-ten graduate student studying medical informatics, shared Barclay’s scrappiness and stature. Despite her tininess, she was a magician with big data analytics. And her innate gravitational pull to help those in need meant that she worked long hours to turn simple numbers into meaningful insights that could save patients’ lives.

  Dustin Shilling, who had just completed his PhD in neuroscience, instilled a healthy skepticism of so-called breakthroughs. As an Alzheimer’s researcher, he had learned all too well about the importance of the scientific method and interrogating results before getting too excited. He pushed for, and contributed his time toward, developing large-scale studies with meticulously detailed designs. The kinds of studies that could stand up in a field as complicated as Alzheimer’s or Castleman disease.

  Jason Ruth, a PhD student studying cancer biology, was my friend before he was my colleague. After joining our clan, he quickly revealed one of his superpowers: He could make connections in his mind between seemingly disparate ideas. That new observation in Castleman disease? There was a cancer research study published in 2005 that could help to explain its importance. Those elevated molecules? Have you seen what other diseases they are elevated in? Biology is intricate and interwoven across species and diseases. Jason made use of all of it to inform whatever problem he was trying to solve. It was sort of like a mountain climber between two faces who uses footholds and handgrips on one to get his way up the other. I envied that kind of thinking—my hyperfocus kept me running straight forward more often than not.

  It wasn’t just Penn graduate students on our commando team. Some of the most important members were already with me. My mother-in-law, Patty, father-in-law, Bernie, and Caitlin also took up the call to arms. Patty became the CDCN’s community coordinator, serving as the primary point of contact for patients, loved ones, and our growing leadership team. She was perfect for it, comforting patients and encouraging volunteers. Bernie became the first member of and a linchpin for an advisory council of leaders in business, law, and medicine who help to guide the C
DCN. Caitlin led our communications efforts, helped with event coordination, and provided daily counsel and candid advice to me. One of Caitlin’s best friends came on board too. Mary Zuccato, an MBA student simultaneously climbing the leadership ladder at Vanguard, managed to jump-start and expand our fundraising efforts; as of my writing this page, we’re finally at about 1 percent of the annual funding for similar rare diseases. Mary became our chief operating officer, which she did as a volunteer on top of her full-time finance work. She was perfect for the role: I’ve never met anyone who more intuitively and gracefully turns ideas into action. She’s a machine for action. Just being around her is motivational.

  Soon, people outside of Penn and my family began to offer to help too. The CDCN leadership team expanded to include other patients, loved ones, physicians, and students—all of us volunteers, each giving anywhere from three to thirty hours each week to the mission: cure Castleman disease. While the hours our CDCN volunteers gave were necessary for our success, it has been their diverse backgrounds and the network’s unique approach that have led to innovative solutions and our accelerated pace of progress. A lot had changed since the days when our “team” consisted of my dad, my sisters, and Caitlin, gathered around a hospital bed, chasing paperwork and cold-calling experts with a mission to just keep me alive. We had scale now—and momentum.

  One person who helped to begin turning our momentum into impact was Raj Jayanthan. Raj became ill with iMCD during his third year of medical school and, like me, had near-fatal organ failure. Just like for me and so many other iMCD patients, doctors at a top-tier medical system couldn’t do anything to slow his disease down. It wasn’t until Dr. Uldrick from the NIH was consulted and recommended a different treatment approach, involving combination chemotherapy, that Raj began to improve. Tom thought connecting Raj and me by email would be a good idea given our shared journeys.

  Our first phone call—three hours long—was just eleven days after Raj was discharged from that frightening hospitalization and I was between my fourth and fifth flares. We immediately bonded over our shared nightmare. We recounted the intimate and eerily similar details of our experiences—we’d both noticed those peculiar blood moles growing rapidly just before becoming sick and we’d both had the surreal feeling of being patients just weeks after walking the same hospital hallways as medical students. Though our symptoms and clinical journeys were almost identical, we had responded completely differently to various treatments. This was an important reminder to me that nothing about Castleman disease was straightforward and that I couldn’t be lulled into thinking that what worked for me would necessarily work for everyone (or anyone) else.

  I was the first Castleman disease patient that Raj had spoken to. I knew what it meant to him, because I still remembered the first patient I met, in Dr. van Rhee’s waiting room years before. But our call also meant so much to me, because it was clear that Raj wanted to help the cause however he could. At the end of our conversation, he asked me to send him the best research papers on Castleman disease, so he could get up to speed.

  My relapse shortly thereafter, in 2013, galvanized Raj’s decision to join the fight. After hearing how sick I got with my fifth episode and remembering how sick he had been himself, Raj took six months off from medical school to dedicate 100 percent of his effort to the most important aspect of the CDCN’s fight at that time: systematically collecting clinical, research, and treatment data in a central database for analysis.

  Recognizing that sirolimus, the drug I was taking for iMCD, had the potential to make a huge difference in my life and possibly the lives of others, we wondered about how many other drugs might already be approved for something else that could help iMCD patients right away. This practice of “off-label” drug use is common, but information on what diseases these drugs are tried on and whether they worked is almost never tracked by the medical system to guide future use. In fact, medical records systems almost never have a specific data field to record whether a treatment is working. And even if they did, physicians and researchers can see medical data only on patients at their own institutions. Disease registries and natural history studies attempt to collect these data for some diseases, but major issues with such studies limit the usefulness of the data. We needed to do better.*

  We needed to create a study to systematically track the various treatments used in Castleman disease and their effectiveness across a large patient population while also collecting as much clinical and laboratory data as possible to start to solve some of the other mysteries of Castleman disease (really this should be done for all diseases). Raj enthusiastically agreed to assist with building the foundation of a Castleman disease registry study to accomplish this. But there was precious little precedent for how to do this well. Like so much else in medicine, there were deep, arbitrary divisions between groups supposedly oriented toward the same goal of curing disease.

  To determine our approach, we evaluated over twenty other disease registries and laid out the pros and cons of each. Some registries were patient-powered, which meant that patients enrolled online and entered data themselves. These registries had the highest patient enrollment numbers, because participants could be recruited online, but they had relatively weaker medical data quality and richness because they relied on a patient’s memory for all data entered, even lab test results, sometimes from hospitalizations years before.

  On the other hand, physician-powered registries involved physicians at a few select sites enrolling patients and entering medical data on them. These registries are more expensive and traditionally have lower patient enrollment, because they’re limited to patients treated at those select sites, but they have much stronger medical data quality and depth. However, the pace of data entry is significantly limited by how busy physicians are with other responsibilities.

  We wanted to figure out a way to combine the best aspects of both approaches into a hybrid model. After months of review and drafting, the plan finally coalesced, fittingly, in the NIH’s clinical center atrium. Tom, Grant, Raj, and I were huddled around a table not far from the one where Tom and I had earlier discussed the possibility of using sirolimus to treat me. Our registry study would be patient-powered, so patients would enroll themselves directly online from anywhere in the world. But rather than rely on patients to enter all their data, we would get permission from them to obtain their complete medical records from their physicians. Then, trained data analysts would enter extensive, physician-quality data from those records into the registry. We’d get the best of both worlds: high patient enrollment and high data quality. And it would happen quickly, because neither patients nor physicians would be burdened with data entry.

  Over several months, we worked with patients and hospitals to figure out how to execute this first-of-its-kind registry study. Frankly, it was astonishing to see so clearly how obstacles to accessing data are such a big part of the dysfunction in medicine. More often than not, the data are out there, ready to be collected, and willingly given up by patients and sometimes by hospital systems. Getting past these hurdles took the will to ignore the status quo and to keep pushing. Raj had that will. I did too. It helped that we both have the disease we hoped this effort would cure.

  But we still needed funding; for starters, it would take a lot of money to hire those expert data analysts. It was time to try to partner with pharma for help. After multiple exploratory calls with officials from a large pharmaceutical company, we had them interested. We were asked to set up a meeting with executives from their North American offices and to teleconference in executives from their European offices. This was a huge opportunity, and we hoped to demonstrate that we weren’t just a group of young patients and physician-scientists in training but that we had an idea worth their support. So we worked on our proposal, and worked some more…and more…and perfected the pitch, and made the slickest presentation possible…After our umpteenth rehearsal, our small team of grad
uate and (barely) postgraduate, mid-to-late-twentysomethings walked into the room just in time for the start of the meeting, only to discover that the conference room didn’t have a working telephone line. None of us could believe it, and despite the collective years of education assembled there, the technicalities of conference calling were lost on us. Suddenly it was four minutes past the scheduled time. Then it was five minutes past. Everybody was either scrambling for a solution or frozen in panic.

  Eventually we went low-tech: We called the teleconference number from my iPhone and then passed it around the room so that each of us could make our portion of the presentation directly into the mouthpiece. I was so frazzled I forgot to mention that I was the executive director of the CDCN or that I was a newly appointed adjunct faculty member in the University of Pennsylvania medical school. I mentioned only that I was an MBA student. But even if we fumbled to make the call work, Raj and I were on a mission, and I suspect that our drive covered up our mistakes that day. If we’d been trying to sell widgets, we would have crashed and burned. But we had a fire burning inside of us for a cause whose success our lives literally depended on, and everyone in that meeting could feel it. And in the end—after another high-stakes meeting at their offices with senior management—they agreed to partner with the CDCN and University of Pennsylvania to establish our international registry study. Raj had already gone back to medical school by that subsequent meeting, but Jason Ruth and Arthur Rubenstein had joined me. The three of us struggled to contain our excitement as we hurried out of the room and through the building. But once we were outside, it all came out—we jumped up and down and cheered (while the pharmaceutical executives were probably watching from their windows!).

  On the two-hour car ride back to Philadelphia, I asked Jason if he could join Caitlin and me for dinner to celebrate. He demurred, explaining that he had to go home to prepare for his PhD thesis defense, which was the next day. I almost drove off the road. Jason had possibly the most important day of his career coming up, when he’d be giving a presentation about the last five years of his laboratory research! But he didn’t want to let me know any sooner, because he wanted to help, even if it meant putting his final defense preparation on hold. Not surprisingly, he passed with flying colors and was recruited to do a postdoctoral fellowship in one of the top cancer research laboratories in the world, at the Broad Institute of MIT and Harvard. As of this writing, he works in biotech venture capital investing and continues to help lead the CDCN as volunteer chief scientific officer.