I grew up in the countryside of Germany, near the Belgian-Luxembourg border. I first became interested in science and medicine in high school, after I broke my leg playing soccer. They gave me spinal anesthesia while they put in screws to stabilize the bone, so I was awake during the procedure. It was fascinating to see everything that was going on. I became interested in anatomy and decided to go to medical school in Aachen, just a few hours from home.
As part of getting my MD, I did an in-depth project on the effect of strokes. This further sparked my interest in neurology and the anatomy of the brain and nervous system. After medical school, I went to the University of Bonn for a two-year residency in neurology. That’s when I began treating people with neurological cancer.
What really intrigued me was people with lymphoma in the brain and spinal cord, known as primary central nervous system lymphoma, or PCNSL. Being fresh from medical school, seeing lymphomas, especially in the brain, was new to me. I have continued to be fascinated with PCNSLs throughout my training and practice.
It still seems strange to me that lymphomas can develop in the brain since there are no lymph nodes there. But immune cells called lymphocytes can travel through the central nervous system and cause cancer. PCNSL tumors are rare. But they’re becoming more common because they usually occur in older patients, and that population is growing.
An Unexpected Turn
I secured a grant to come to Case Western Reserve University in Cleveland for two years as a research fellow to continue studying brain tumors. Just a few months after starting, I developed a brain tumor myself. It was a choroid plexus papilloma, a rare noncancerous tumor that usually develops in young children.
The surgery went well, but everything else that can go wrong did. I had meningitis and I needed to do rehabilitation. It was eye-opening to see how fast my health could deteriorate. Before my diagnosis, I was 27 and in good health. But suddenly I could not walk up and down stairs. It really made me aware of what it’s like to be a patient, to be on the other side. That has stayed with me to this day and affects how I approach patients myself.
Putting Down Roots
I was able to finish my research at Case Western. I stayed in Cleveland for the next four years as a resident in neurology, continuing to specialize in treating brain tumors. While there, I met my wife and started a family. After finishing residency, I was drawn to Memorial Sloan Kettering due to its leadership in neuro-oncology and in PCNSL research and treatment. I came to MSK in 2009 to train as a neuro-oncology fellow, and we decided to move the family to New York and stay here. After two years, I joined MSK permanently as a neuro-oncologist and neurologist.
Toward Better Treatments
Over the past few decades, we’ve learned that the chemotherapy drug methotrexate (Rheumatrex®, Trexall®) allows people with PCNSLs to live for a long time. But the drug provides a cure in only about half of patients and it can cause significant side effects. As I began my MSK fellowship, it was clear we needed better treatments. I was in clinic with [neuro-oncologist] Ingo Mellinghoff, talking about what more could be done. We realized we needed a better understanding of what causes these PCNSL tumors to grow.
With funding from the American Brain Tumor Association and the strong support of Dr. Mellinghoff and [neuro-oncologist and Physician-in-Chief] Lisa DeAngelis, we established a large PCNSL tumor tissue bank. We collected tumor samples and looked for the genetic mutations underlying the growth of these cancers. This enabled us to identify a pathway that drives PCNSL, called the B cell receptor pathway. One protein critical to this pathway, called Bruton’s tyrosine kinase (BTK), can be targeted with drugs.
At the same time, we were collecting samples from newly diagnosed patients and creating disease-specific animal models. This allowed us to test drugs targeting BTK.
Beginning in 2014, and based on the preclinical data collected, we launched a clinical trial testing a BTK inhibitor called ibrutinib (Imbruvica®), alone or combined with different chemotherapies, in people whose PCNSL had resisted initial treatment or returned. Fortunately, we found that ibrutinib had activity in these patients. Ibrutinib is now part of the national guideline to treat people whose PCNSL has resisted initial treatment or returned.
The findings from our laboratory and clinical trial have helped invigorate the field. We are able to offer other treatments to patients who cannot tolerate the side effects from chemotherapy. In the next few years, I would like to begin including targeted therapies, such as ibrutinib, in the first line of treatment. We hope to get better results and have fewer people be resistant to the therapy.
Gratitude and Grace
MSK has a very nurturing environment in which to do research and investigate ideas. Dr. Mellinghoff’s creativity in tackling scientific questions and getting things done has been amazing. It’s shaped the way I approach things. In addition, I am so grateful to Dr. DeAngelis, who is such a prominent figure in the field, for giving me her time, support, and clinical guidance to develop our PCNSL research program.
The most gratifying part of my work is giving good care to patients. As a doctor, it is very rewarding to treat people with PCNSL because treatments can be quite effective. You see very sick patients recover quite quickly, which sadly is not the case with some other brain tumors. I love talking to someone who has been told at other places that nothing can be done to help them, and I can say, “We have a clinical trial.”
Another thing that drives me is knowing I was lucky enough with my own brain tumor. After my surgery, I shared a hospital room with a man who was about my age, already married with a child. Based on what he was telling me, I knew he likely had a malignant glioma and was facing a very grim outlook, probably death, in the next few years. He was much sicker than I was, but the whole time he was concerned about me and how I was doing. And that still motivates me today. How can I help people like him? If I ever get frustrated or discouraged about things, I think of him and it keeps me going.