Where Are They Now? John Pagel, MD, PhD

When did you become interested in the study of medicine? In lymphoma specifically?

When I was a kid, I was interested in two things: sports and science! Some of my earliest memories were of dissecting bugs in my parents’ garage — I was highly fascinated with how biology worked. Once I realized that a career as a professional baseball player would not pan out, I decided that I should maybe take a path toward science. I went to graduate school for the love of science and got a PhD before going to medical school, where I desired the human component for research. While in medical school, my mother was diagnosed with metastatic breast cancer. This motivated me to pursue a career in oncology. Subsequently, I was drawn to lymphoma because I was interested in technologies that could be developed in hematologic malignancies that could be translated broadly across all cancers — perhaps even to breast cancer.

At what point in your career did you receive funding from the Lymphoma Research Foundation? What kind of grant(s) did you receive?

I received a Career Development Award from the Foundation when I was a junior investigator trying to make my way forward in my career. It was the first real accolade I was able to put on my resume, and it helped me stay dedicated, focused, and interested in what I was doing. This award was really the kick-start to my career in lymphoma-related research.

What scientific project did you pursue as part of your research grant(s)?

One thing that often happens in cancer research, that is important to remember, is that when you apply for major funding, usually from federal government entities such as the National Institute of Health (NIH), those grant applications often need to be based on years of prior research. This usually signifies that the project is worth pursuing further, and in fact, in many ways, it might already show clear promise.

However, that’s not always how research is done, and early projects need support for biologically driven yet still unproven exploration. At the time, I was interested in the idea and use of targeted delivery of radiation and how we could find better ways to deliver radiolabeled antibodies so that we could get more of the radiation delivered to the lymphoma cell and less of it delivered to normal organs. We came up with a two-step concept called “pre-targeting” where we could decouple the antibody from the radionuclide. This would allow us to deliver the antibody to the patient to target the lymphoma cell and then use the radionuclide later to find the antibody that’s already localized to the lymphoma. Overall, this approach allowed for the delivery of much higher doses of lymphoma-sensitive radiation than could be delivered with external beam radiotherapy or even standard one-step radiolabeled antibody therapy.

How has the treatment landscape for lymphoma/CLL changed since you first started conducting your research?

It’s been an incredible opportunity to see how things have changed. Not long ago, all we had to treat all our lymphoma patients was cytotoxic chemotherapy, and it was common in those days to inflict significant morbidity to patients. Now, with novel non-chemotherapy regimens, we have reduced toxicities and dramatically increase rates of cure for lymphoma patients. Obviously, to be part of something so humanly valuable and revolutionary has personally been immensely rewarding.

Was the support and grant funding you received from the Foundation vital to advancing/ dedicating your career to studying lymphoma?

The Foundation support was an integral part of my career development that had a domino effect on the rest of my career. It gave me an opportunity to start my own research lab and receive subsequent awards to continue my research. The Foundation recognized my project as a novel idea worth pursuing, and without the funds provided to me by them, I am not sure that I would have ever been able to dedicate my whole career to lymphoma-related research.

Why is there such a great need for lymphoma/CLL research? Why is a greater investment needed?

The progress we have made for patients is truly a testament to why research is so important. Without support for research, as well as critical patient advocacy that organizations like the Lymphoma Research Foundation does, we would not have made those progressive strides. These strides have been dramatic, but we still have a long way to go. We need to cure everyone, and that is why supporting research continues to be important. We need to foster and develop innovative ideas and invest in the careers of the investigators who are doing the work.

How has your involvement with the Foundation evolved since being a grantee, and how has the Foundation shaped your role in industry?

I have had a long relationship with the Foundation and am grateful to bear witness to the difference it makes in the lives of patients, their loved ones, and the scientific community. I have been lucky enough to be involved in many of their programs and initiatives, including opportunities to directly connect with patients and provide education and support. Now that I’m in an industry position at Eli Lilly and Company, I am still active and involved with the work that the Foundation does and can support them in new ways, such as helping to fund and support their research and education resources as well as support services.

Why is the Foundation’s mission and focus on lymphoma-specific research and programming important? Put another way: How would the lymphoma community be impacted if there was no Lymphoma Research Foundation?

Lymphoma research investigators need support, direction, and encouragement to navigate the often difficult times in their career development. Specifically, it is incredibly important to support investigators who are doing work that can take years to develop to get something from the bench to the bedside. Without organizations like the Lymphoma Research Foundation, I do not think we can offer that level of support and make the strides that we make in curing patients. Additionally, without the Foundation, patient advocacy in the lymphoma space would be sparse and devastating for patients without those kinds of resources. It is always scary and overwhelming to get diagnosed with lymphoma, and having a resource like the Foundation is critical to navigating the lymphoma journey. Being aligned with the Foundation as a key patient advocate translates to the best care that patients will receive.

What priorities are you currently pursuing that you would like to share with our readers?

We are deeply focused on developing medicines that improve patients’ lives. We do so by focusing on the biological conviction of a target, pathway, or biochemical feature of a malignant cell that would allow us to develop a medicine. It is an arduous process in many ways, but the strides that are being made collectively will continue to be groundbreaking.

What is the most exciting thing happening in lymphoma research right now? What are you most excited about in the field of lymphoma research in general? Why?

I think the most exciting thing happening in lymphoma research continues to be the development of novel targeted therapies. A good example is the continued development of targeted bispecific antibodies that allow for control of disease without chemotherapy. Patients may still relapse, but they will continue to have increase opportunities to change this disease’s natural history. Clearly, we have many strides still to make, but it has been a rewarding experience to be part of, and I know we will continue to move lymphoma therapies in a positive direction.