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Despite her high profile, Dr. Courtney DiNardo shies away from the spotlight. I am grateful that she took the time to provide insight into the evolution of her career and recent advances in employing “epigenetic targeting” therapies in the treatment of AML.

ASH News Daily. Your work as a clinical trialist has been integral to the translational development of mutant isocitrate dehydrogenase (IDH) 1/2 inhibitors in AML and related myeloid neoplasms with those respective IDH mutations. How did you first become involved in studying these mutant enzymes and later compounds targeting them?

Dr. Courtney DiNardo. Classic story of being in the right place at the right time. My original (fellowship project!) with Dr. Martin Carroll on IDH1 and IDH2 mutations in AML helped define the relationship and significance of the unique 2HG oncometabolite, which occurs specifically in the setting of IDH mutations. This project involved analysis of stored ECOG samples, and so through working on this project I was able to meet and collaborate with many leaders in the AML field, within and outside of my home institution, including the scientists at Agios who had developed the 2HG assay.

My early involvement in the IDH story, and then my transition to the Leukemia Department at MD Anderson as a clinical investigator, led to my role as an investigator on the first clinical trials of the small molecule targeted IDH inhibitors, ultimately leading to FDA approval of the first-in-class IDH2 inhibitor enasidenib and the IDH1 inhibitor ivosidenib. 

AND. There are often inflection points in one’s career where a particular opportunity or decision markedly shapes their professional trajectory. What has been such an “inflection point” in your own career, to date?

CD: The credit for this really goes to Dr. Hagop Kantarjian. I was a brand-new junior faculty in one of the largest and most productive leukemia groups – so his support and guidance in helping me take on the PI role of the first in human mutant targeted IDH inhibitors is really what allowed me the opportunity for such early success in these transformative clinical trials.

AND. We all see further “standing on the shoulders of giants.” What person or people, either within or outside of hematology-oncology, have been influential in your professional development?

CD: Selina Luger: Such an inspiration! I wanted to model my whole career after her. Dr. Luger is a successful, strong, (and only mildly intimidating) female leader who is loved and respected by colleagues and patients alike. Somehow, she made it look easy and enviable to manage a full clinic, run a leukemia program, chair various ASH and ECOG programs, all the while balancing a two-physician household with two school-aged daughters. Incredible.

Martin Carroll: Dr. Carroll taught me the joy of being a life-long learner. His advice to me at the beginning of my training was spot-on: Choose a topic or subfield I was passionate about and become the expert on it. Know it inside and out so people seek out your expertise. Little did we know how that first project on IDH mutations would shape the entire trajectory of my leukemia career.  

Hagop Kantarjian: I have never met anyone who believes more wholeheartedly that there is always room for improvement – in everything. His advice is simple and powerful: Work hard and never settle. Stand strong, and advocate for what you believe in. Keep thinking outside the box, because our patients depend on us to continue to advance the field as our standard of care is not good enough.

AND. What is a critical question that remains to be answered about the application of “epigenetic targeting” therapies, including mutant IDH inhibitors, in AML and related myeloid neoplasms?

CD: How to best use them! Just think about it — ATRA for APL is amazing — but not curative when used alone. So, we still need to learn what are the best ways to combine these therapies, with what, and what time is the best time to use them (upfront, in maintenance, etc.). And how great would it be to know which patients obtaining remission are cured and which have low level residual/resistant disease, so we know who would most benefit from transplant, and who could actually stop therapy?

AND. Clinical practice is constantly evolving, and we are all doing our best for patients. However, what practice that we as a community routinely do now in the management of AML do you think in 20-30 years will seem rather absurd?

CD: That’s a fun question. I wonder if in 20 to 30 years our leukemia-directed therapies (including of course AML immunobiology approaches) will have improved to such a significant degree that the role of allogeneic stem cell transplantation will be markedly different.

Interview conducted by ASH News Daily Author Dr. Danielle Hammond.

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