Dancer to Doctor: Dreams Fuel Top Lymphoma Researcher’s Success

How would you describe the growth and success of the lymphoma program you launched in 2014?

In 10 years, thanks to the support of a steadfast leadership, we went from a program of one physician (me) to a total of five dedicated lymphoma clinicians. I’m very proud and humbled to say that our program has some of the most exceptional outcomes for lymphoma in the nation. We have also had remarkable – knock on wood – success with our clinical trials with nearly 80% of our clinical trial drugs getting FDA approved. This means our patients received the benefit of path-breaking medications at least four years prior to their approval. Our focus is primarily targeting chemo-free, efficacious but less toxic approaches to treatment, where we are trying to harness one’s own immune system to tackle and beat cancer.

What do you consider your biggest achievement so far in that endeavor?

I think we have fortunately been able to contribute toward better health and outcomes for our patients through our patient-centric approach and our ability to offer promising treatments through clinical trials for those patients where cure was not possible. I think the biggest clinical development that clearly unleashed the potential of chemo-free approaches to cancer would be a targeted inhibitor called Calquence (acalabrutinib). It’s a pill, and it went on to become FDA approved for patients with chronic lymphocytic leukemia. Patients are taking pills for cancer like people with high-blood pressure do. They don’t have a lot of side effects, and the chance of response is 80% to 85%. Prior to these targeted inhibitors, all there were in the field were chemotherapy agents, which were not highly effective but were highly toxic.

CAR (chimeric antigen receptor) T-cell therapy has taken the oncology world by storm, and you have been right there at the forefront of its development. Could you talk about your specific work with this immunotherapy?

I would say that has been our other big achievement. The CD19 CAR T-cell therapy study helped open the floodgates. We worked with the initial studies with lisocabtagene maraleucel (liso-cel) CAR T therapy. Subsequently, we opened four other liso-cell trials, and all these studies went on to FDA approval.The biggest advantage that liso-cell provided was in patients who had failed two or more lines of chemo treatments for a lymphoma called diffuse large B-cell lymphoma (DLBCL). With CAR T therapy, 40% of patients who could have otherwise succumbed to their disease actually were cured with liso-cell.

In oncology, what works in later lines typically gets tested in earlier lines with the hope that the benefit can be given to patients sooner. I think our biggest win so far for our patients has been liso-cell approval as a second-line therapy for DLBCL. Historically, of patients who had failed or progressed after frontline chemotherapy for DLBCL, about 50% did not get cured. For them, the answer was more intense chemo, and if they responded, bone marrow transplant. And it was quite known in the field that for these patients, bone marrow transplant success rates were only 15%.

So, we participated in these randomized studies and eventually championed it and spearheaded it as a first-author publication. In the trials, patients who had relapsed after receiving front-line chemotherapy were randomized to either getting the standard of care consisting of more chemotherapy and bone marrow transplant or getting CAR T-cell therapy at relapse. And CAR T-cell therapy won hands-down and became the new standard of care, displacing a two-decade-old standard of care.

What are you working on right now that really excites you?

Answering the question: What happens when someone progresses after CD19 CAR T-cell therapy? We have some exceptional clinical trials that are ongoing to answer that, and one of them is actually our very own, called the UCD 19-22 CAR. This is really about tricking the cancer by manufacturing a CAR that has the potential to bind to not one but two proteins on the cancer cell: 19 and 22. And so far, we have had some promising success.

This interview was edited for length and clarity.