A doctor with a potentially fatal condition has been in remission for five years after testing an experimental treatment on himself.
Dr David Fajgenbaum, who works at the University of Pennsylvania, was diagnosed with an aggressive form of Castleman disease in 2010, aged 25. It triggers an abnormal overgrowth of cells of the lymph system, which can cause multiple organ failure.
His form of the condition, called idiopathic multicentric, kills around a third of patients within five years, according to figures.
But he is still alive today, after gambling on a drug called sirolimus. His technique also helped two other patients go a year-and-a-half without a flare-up.
Dr David Fajgenbaum, who works at the University of Pennsylvania, was diagnosed with an aggressive form of Castleman disease in 2010. It causes an abnormal overgrowth of cells of the lymph system, which can cause multiple organ failure
His form of the condition, called idiopathic multicentric, kills around a third of patients within five years, according to figures (it is unclear who he is pictured with at the 4th Annual RARE Tribute to Champions of Hope Gala in September 2015)
Dr Fajgenbaum’s own research into the condition, prompted by his diagnosis, suggested it may work by blocking a crucial pathway.
Blood tests he had taken along the way showed a spike T cells before suffering a flare-up, which includes fatigue, fever and night sweats.
And they also revealed an increase in the levels of a protein called VEGF-A. Both can be kept under control through the PI3K/Akt/mTOR pathway.
Sirolimus, or rapamycin, works through this same mechanism, which gave Dr Fajgenbaum enough hope that it could help him.
He decided to test the drug on himself, after consulting with Dr Thomas Uldrick, senior author of the research and Dr Fajgenbaum’s physician.
And now he has reported his remission – and that of two other patients taking the same drug – in the Journal of Clinical Investigation.
Sirolimus is already available for the treatment of other conditions, particularly to prevent organ rejection after kidney transplantation.
But he is still alive today, after gambling on a drug called sirolimus. His technique also helped two other patients go a year-and-a-half without a flare-up
Dr Fajgenbaum, a former Division I quarterback and weight-lifter, was a medical student when he was struck down in July 2010.
He began researching his condition in 2012, after failing to respond to treatments including an approved drug and chemotherapy.
‘Patients who don’t respond to siltuximab (Sylvant) have limited options. They typically receive chemotherapy but often relapse,’ he said.
Tests showed that both the other patients, who also had the same form of Castleman disease, also had the same spikes before a flare-up.
They have both gone 19 months without relapsing after taking sirolimus, Dr Fajgenbaum and colleagues wrote in the scientific journal.
‘Our findings are the first to link T cells, VEGF-A, and the PI3K/Akt/mTOR pathway to iMCD,’ said Dr Fajgenbaum, who works at the Perelman School of Medicine.
‘Most importantly, these patients improved when we inhibited mTOR. This is crucial because it gives us a therapeutic target for patients who don’t respond to siltuximab.’
Siltuximab is currently the only drug approved by the US Food and Drug Administration to treat the aggressive form of Castleman disease.
Dr Fajgenbaum and colleagues are to begin a clinical trial on the drug in the coming weeks, in hope of finding another treatment for patients.
WHAT IS CASTLEMAN DISEASE?
Castleman disease isn’t actually a single disease. Instead, it is a group of inflammatory disorders that cause an abnormal overgrowth of cells of the lymph system.
It’s diagnosed in about 5,000 people of all ages each year in the US, which makes it roughly as common as Lou Gehrig’s disease, also called ALS.
Patients experience a range of symptoms – from a single abnormal lymph node with mild flu-like symptoms to abnormal lymph nodes located throughout their entire body, abnormal blood cell counts, and life-threatening failure of multiple organ systems, such as the kidneys, liver, heart, and lungs.
The most severe subtype, idiopathic multicentric Castleman disease (iMCD), has similarities to both autoimmune conditions as well as cancer.
About 35 percent of patients with iMCD will die within five years of diagnosis.
In 2014, the FDA approved the drug siltuximab to treat iMCD, and studies have shown it can send between one-third and one-half of patients into a remission that generally lasts for years.
Source: University of Pennsylvania