Researcher Responsible for CLL Breakthroughs Honored by ASH

John C. Byrd, MD, discusses receiving the American Society of Hematology's 2015 William Dameshek Prize for his numerous therapeutic breakthroughs in chronic lymphocytic leukemia, his impactful career, and his goals for the future.

John C. Byrd, MD

John C. Byrd, MD, has been awarded the American Society of Hematology’s (ASH) 2015 William Dameshek Prize for his numerous therapeutic breakthroughs in chronic lymphocytic leukemia (CLL) throughout his 20-year career. This prize, named after a late past president of ASH and the original editor of Blood, recognizes outstanding contributions to the field of hematology.

Early in his career Byrd, who is director of the Division of Hematology and a CLL specialist at the Ohio State University Comprehensive Cancer Center, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC—James), developed and defined the mechanism of action of the anti-CD20 antibody rituximab (Rituxan), the first therapy to prolong survival in CLL.

Later in his career, Byrd continued to impact the outlook for patients with CLL, serving as a key player in the preclinical and clinical development of ibrutinib (Imbruvica), an advance that disproved the widely held notion that only cancers with a single molecular target could be treated with targeted therapy.

Since the FDA’s 2013 approval of ibrutinib, Byrd has continued to facilitate research addressing drug resistance and explore alternative treatment strategies. His current focus is on the continued development of targeted and immunotherapies in CLL. He has also expanded his focus to include the development of novel therapies for acute myeloid leukemia (AML).

In an interview with OncLive, Byrd, who is also the D. Warren Brown Chair of Leukemia Research at The Ohio State University College of Medicine, discusses the national honor, his impactful career, and his goals for the future.

OncLive: How does it feel to be a recipient of the 2015 William Dameshek Prize?

Dr Byrd: Winning this award and being recognized for the team’s effort is very humbling. However, I think it should be a team award because so many people have been involved in our research.

Taking ibrutinib from the lab and helping it become a drug that is really changing how we treat CLL is very exciting, as was our earlier success with rituximab. This is truly what all scientists go into the lab to do and what doctors aim to do with patients.

How has the treatment of CLL evolved throughout your career?

Thirty years ago, we had one therapy for CLL. What has been fun is seeing how, from the early 1990s to now, our understanding of the biology of the disease has evolved. A CLL diagnosis used to mean you only had a few options. Today, we have therapies that target the cancer cell and allow patients to get better and stay better with very durable remissions. We are treating the disease in a way that is becoming similar to how we treat high blood pressure or diabetes; when you go on medication—and as long as you stay on the medication—the disease is controlled.

Now, we are entering another era where there is a chance of curing CLL. Hopefully, the move will be making is to take all of this biological data and novel therapies and combine them into curative therapies for all patients with CLL. That is going to be the next challenge. It is great to have seen things evolve over the past several decades. There is work that we did in the laboratory that has gone to the clinic that is going to make an impact for patients.

How has rituximab evolved since you first defined its mechanism of action in CLL, and where do you see it going next?

Rituximab was very interesting in CLL because it had very little activity when it was first included in clinical trials. The first step we had was showing that rituximab had activity, and part of that was determining that it had to be administered differently. We would see patients benefit, but then realize that the benefit was not long-lasting.

We realized that more of the antibody needed to be administered; that matched the biologics of the disease. It was a phenomenal experience to dose someone with rituximab and see their leukemia count go from 100 to 1 in 24 hours. Compared to historical controls, we were really making a big difference in survival in how long people were living. When you looked at the curves, it was not a small difference.

Prior to your research, it was believed that only cancers with a single molecular target could be treated with targeted therapy. What first got you interested in investigating ibrutinib for CLL?

We got involved with ibrutinib because of our interest in targeted therapies. It looked different because it stopped CLL from growing and sort of strangled the cancer cells in the microenvironment. As you get into news drugs, you have to throw out everything you know and just be open. You have to always be thinking about the potential of your data, even if it’s modest. You have to make lemonade out of lemons. If we had relied on preclinical data, the drug would probably never have been considered.

Once we started working with it in the clinic, we saw many of the same paradigms people went through with chemotherapy. A lot of the initial ideas had to be redesigned and thrown out. Now, we have ibrutinib and other BTK inhibitors that have the potential to even build upon ibrutinib and eliminate patients’ tumor cells, restore the immune system, and really fight the disease. The journey with ibrutinib has really been phenomenal. I have been waiting for the other shoe to drop and it just has not. This class of drugs just seems to become more and more promising. It makes coming to work not feel like work, because we are delighted to be doing something that we know is going to be impactful for patients.

What does your research currently focus on?

Our lab is really focused on targeted and immune therapies in CLL. We are also transitioning to applying these same therapies in AML. After being one of the team members of something that has been successful such as ibrutinib or rituximab, I want to continue doing impactful work. I want to take on a bigger challenge. We may not succeed at all in applying these principles to AML, but we want to give it a shot because we feel there is a need there. My efforts over the next decade are to contribute to that disease, as well.