Rare Individual, Unique Fight

David Fajgenbaum is battling a little-known, extremely deadly disease as a researcher, a physician, an advocate, an entrepreneur and a patient.

By Carole Bernstein | Photos by Rebecca McAlpin

David Fajgenbaum is battling a little known, extremely deadly disease as a researcher, a physician, an advocate, an entrepreneur and a patient.

In August 2010, David Fajgenbaum M13 WG15 was a third-year student at the University of Pennsylvania School of Medicine, with, as he says, “a complete laser focus on becoming a clinical oncologist.” He was living the life of a typical medical student: doing clinical rotations, studying, checking on patient labs and orders, working crazy hours and getting little sleep. But for Fajgenbaum, 2010 would turn out to be anything but typical.

Over a two-week period, he started experiencing fatigue, night sweats and stomach pain. At first he thought it was the flu, but the pain got so bad he finally went to Penn’s emergency department. “They did blood work and said, ‘You’re not leaving the hospital,’” Fajgenbaum recalls. Inexplicably, the young medical student was showing signs of liver, kidney and bone marrow dysfunction.

“Over the next week, I completely fell off the cliff,” says Fajgenbaum. While in the ICU, every one of his major organs began to fail. He also suffered retinal bleeding and blindness in his left eye and gained 70 pounds of body fluid, a condition known as anasarca. There was still no diagnosis.

“So all we’re seeing is me dying. My whole family came to town; in fact, I picked the six friends who I wanted to come so that I could say goodbye to them,” says Fajgenbaum.

The doctors at Penn decided to try high-dose steroids. He started to improve, and after seven weeks of treatment he was actually able to walk out of the hospital. But he left there, he says, with “no idea of what almost killed me.”

Although Fajgenbaum survived, he is far from being out of the woods. It turned out he has a rare, poorly understood condition called multicentric Castleman disease (MCD). It still lurks in him without a cure, a condition with a 35 percent five-year mortality rate, worse than lymphoma and prostate and breast cancer. He has had four other near-death relapses. During the second episode in November 2010, his family’s priest was called in and administered last rites. The last two occurred 15 and 17 months after combination chemotherapy, and it’s been 18 months since.

LIVING EVERY MINUTE, EVERY HOUR

Today, Fajgenbaum is a research assistant professor of medicine in the division of hematology/oncology at Penn. He also just completed an MBA at Wharton. He is the co-founder and executive director of the Castleman Disease Collaborative Network (CDCN), a research and patient support organization he started in August 2012. Last May, he got married, and around the same time published a paper in the prominent hematology journal Blood, which is acknowledged to have helped advance medicine’s understanding of the mechanism behind Castleman disease. This year, he was named one of the Forbes “30 Under 30” in the health care space.

Put simply, he is a busy guy. And to talk with him—a fit, energetic, confident young man in his late 20s, with a logical yet personable way of explaining things—one would never suspect that he had been so ill and had more than one brush with death. Yet there is an undefined intensity about him, which might stem from being someone who regards the hours and minutes of each day differently from most.

“I feel fantastic. I feel totally normal,” he comments. “This disease is interesting in that it’s so episodic,” he adds, with a doctor’s clinical detachment. “I can go from feeling 100 percent like I do right now, to being on my deathbed within a matter of weeks.”

David Fajgenbaum is battling a little known, extremely deadly disease as a researcher, a physician, an advocate, an entrepreneur and a patient.

Castleman disease, Fajgenbaum explains, involves the immune system becoming activated and releasing inflammatory proteins called cytokines. The immune system is normally the body’s defense mechanism. But with Castleman disease, “it’s almost like my immune system doesn’t have brakes, so when it turns on it just keeps going and going.” When it can’t be turned off, it’s deadly: the cytokines will shut down your organs and kill you.

Doctors aren’t even sure how to classify Castleman disease, a condition named for Benjamin Castleman, a Massachusetts physician who first published about the condition in the mid- 1950s. Fajgenbaum describes it as “sitting right at the intersection between a cancer and an autoimmune disease.” The American Cancer Society’s website states that it’s not known how many people are diagnosed with Castleman disease each year (5,000 is the rough estimate). Because it has not been defined as a cancer, the National Cancer Institute doesn’t track it.

And there is no standard treatment. A glance at a commonly consulted medical website—for example, the Mayo Clinic— reveals a laundry list of options including monoclonal antibodies, chemotherapy, corticosteroids, antiviral drugs and thalidomide (which unfortunately evokes the words of playwright Anton Chekhov in The Cherry Orchard: “If there’s any illness for which people offer many remedies, you may be sure that particular illness is incurable”).

Moreover, according to Fajgenbaum, stronger and stronger medications have been necessary each time he has relapsed. By the third relapse, while being treated by the world’s expert on Castleman disease—Dr. Frits van Rhee, based in Little Rock, Arkansas—the steroids that had saved his life at Penn didn’t work, even at “the highest doses you can give to man.” A double dose of rituximab, which previously had afforded him partial remission, didn’t work. Nor did an experimental drug for which the Food and Drug Administration granted emergency compassionate use. Finally his doctor “hit the dynamite,” in Fajgenbaum’s words, and administered a seven-agent chemotherapy cocktail. After several weeks he was able to be discharged.

Yet, Fajgenbaum notes, this type of chemotherapy is only a stopgap. It works by eliminating the immune system, but the immune system eventually returns. And there is a lifetime limit; every additional dose actually puts a patient at risk of developing a cancer. A new, targeted MCD drug called siltuximab became FDA-approved in 2014. This was a major breakthrough for the community, but the drug was effective in only 34 percent of MCD patients in the clinical trial.

REMODELING MEDICAL RESEARCH

“I realized I was not going to survive, and that this disease was going to kill me if I didn’t start getting involved and trying to move science forward,” he says.

This in a nutshell is what prompted Fajgenbaum to found the CDCN in August 2012. He recalls that during his fourth hospitalization with the disease in May 2012, “it really hit me in my face that all of these papers that’ve been written about Castleman disease, and all of the experts around the world, don’t understand how this disease works.”


“I realized I was not going to survive, and that this disease was going to kill me if I didn’t start getting involved and trying to move science forward.”

Together with Dr. van Rhee and with the support of Dr. Arthur Rubenstein, then-interim director of the Penn Orphan Disease Center and former dean of Penn’s medical school, Fajgenbaum set up the CDCN. Rubenstein, a Penn professor of endocrinology, now serves as a senior medical advisor on the CDCN Leadership Team. He calls Fajgenbaum a “born leader,” commenting, “He’s a young person, I mean he’s just graduated medical school, doing his MBA, yet he leads a world group of scientists … somebody they all follow and listen to and believe in.”

The medical community had believed that benign lymph node tumors, which secreted cytokines and activated the immune system, caused MCD. Fajgenbaum’s aforementioned paper in Blood flipped this model on its head. He found that elevated levels of cytokines and an activated immune system enlarged the lymph nodes. This is an important distinction, because immunosuppressive agents may be effective for treating MCD. Now, the CDCN is searching for what could be activating the immune system and how to effectively intervene. (Fajgenbaum’s current immunosuppressant treatment is based on this, his own research finding.)

In addition to advancing research, the CDCN serves as a resource for patients. Mileva Repasky, a clinical psychology graduate student from Killeen, Texas, found the CDCN online after her 15-month-old daughter Katie was diagnosed with MCD. Now 3 years old, Katie is continuing to undergo courses of chemotherapy drugs, some of which have never been used on a pediatric Castlemans patient.

“She is probably the youngest ever diagnosed, so we are pretty much the guinea pigs,” explains Repasky.

Repasky asked to be a part of the CDCN, and now volunteers, from her home in Texas, on the communications team.

“I feel like I’m actively having a role in trying to fix my daughter, which really helps,” she says.

Of Fajgenbaum, she says, she has appreciated that he “connects with every single patient who comes across his path; he makes everybody feel like he really is going to tackle this disease for them.” She adds, “Most doctors, if they don’t know something, are not really willing all the time to branch out and get other people’s advice and opinion. And I feel like David is always willing to learn more.”

BESTED BUSINESS CHALLENGES TOO

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Why does a medical professional battling a deadly disease decide to go for an MBA? Fajgenbaum says that the greatest hurdles he’s encountered have been not scientific but business related. He believes that the standard research model—in which individual scientists apply for funding to research a particular type of disease and then use the money as they see fit—is flawed. “There’s no strategy … there are limited tools for collaboration between researchers; there is inefficient use of available research samples and funding.”

Especially with a rare disease like Castleman for which funding is limited, Fajgenbaum believes, it is critical to “make every dollar count.” The CDCN has taken an innovative approach that involves first connecting all the Castleman researchers worldwide through meetings and online discussions. Then the community identifies priority research projects, and the CDCN recruits top experts to take them on, offering funding, samples and logistical support.

This year, the network expects to spend about $200,000 on five research studies, Fajgenbaum reports. That’s equivalent to about 2 percent of the funding spent on other similarly rare and deadly diseases. Twelve more high-priority studies “with major impact potential” are on hold until the CDCN raises the money to launch them.

Fajgenbaum has enlisted the help of other Wharton MBA students for the CDCN as well; in fact, about half of the team are Wharton students. One current effort, with which Andrew Towne L15 WG15, Patrick Morey WG15 and then-first-year student Tina Chong are involved, is to reduce the red tape surrounding crossborder tissue transfer in order to speed precious lymph node samples to a CDCN-Columbia University study. MBA students have also mounted fundraisers among the Wharton community this spring, including the “Knock Out Castleman Disease Campaign” and the “Boot Camp to Beat Castleman Disease.”

“The community has jumped behind this, and it’s been remarkable,” says Fajgenbaum.

CDCN is not the first advocacy group Fajgenbaum has founded. In 2006 as a Georgetown University undergraduate, he started National Students of AMF, a nonprofit organization to support grieving college students. AMF stands for “Ailing Mothers & Fathers” and the initials of his mother, Anne Marie Fajgenbaum, who died from brain cancer when Fajgenbaum was a sophomore. Today, there are about 55 active chapters around the U.S. (On Fajgenbaum’s wrist, one notices a red-and-white rubber AMF bracelet.)

Dr. Bette Jacobs, former dean of the Georgetown University School of Nursing and Health Studies, knew Fajgenbaum in his undergraduate days, and notes that his generosity and helpfulness toward other students stood out in the competitive premed environment. Along with others, she lauds Fajgenbaum’s ability to bring people and resources together.

“He’s a good connector,” she says. “He inspires people. And I think it’s because we identify—[maybe] not precisely with what he’s going through—but with what we would hope adversity could teach us.”

—Carole Bernstein is a freelance writer based in Philadelphia who has covered health and business topics for a number of publications.

Connect with Dr. Fajgenbaum
Learn more about Castleman disease and the CDCN (and donate if compelled to) at: http://www.cdcn.org/wharton.

 





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