"Entering the Era of Precision Medicine in Acute Myeloid Leukemia” – Dr. Guillaume Richard-Carpentier
Melinda Chelva, MSc Candidate (Translational Medicine)
It was a pleasure and privilege to hear Dr. Guillaume Richard-Carpentier present "Entering the Era of Precision Medicine in Acute Myeloid Leukemia (AML)" at the Medical Grand Rounds last week. Dr. Richard-Carpentier provided an overview of the clinical and genetic heterogeneity of AML, the recent evolution of AML treatment, and the challenges related to precision medicine.
AML is a hematological malignancy that arises as a result of mutations in hematopoietic stem cells- commonly due to genetic predispositions, or prior exposure to chemotherapy and radiation (1). Epigenetic dysregulation is very common in AML patients; unfortunately, it increases the genetic variation of AML, and overall, enhances the challenge of developing effective treatments that will cater to all AML patients (1). Throughout his presentation, Dr. Richard-Carpentier highlighted that the diversity in co-occurring mutations increases the heterogeneity of AML, which drives the complexity of the disease and dictates the prognosis of patients.
Prior to 2017, intensive chemotherapy was the most common treatment for AML patients; however, the ability for leukemia stem cells to resist chemotherapy and result in relapse, has always been a major drawback to this approach (2). Dr. Richard-Carpentier highlighted eight new drugs that have been approved for the treatment of AML in the past three years (2). These include fms-related tyrosine kinase 3 (FLT3) inhibitors, gemtuzumab ozogamicin (GO), CPX-351, isocitrate dehydrogenase 1/2 (IDH1/2) inhibitors, and B-cell lymphoma 2 (BCL-2) inhibitors (2). Overall, Dr. Richard-Carpentier’s research reveals the significant shift in AML patient care- treatments have progressed from the “one-size fits all” approach, to now successfully targeting specific mutations.
Dr. Richard-Carpentier revealed the success of these novel therapeutics in clinical trials. Notably, he highlighted that adding FLT3 inhibitors to intensive chemotherapy increases the overall survival of AML patients (3). Additionally, Dr. Richard-Carpentier explained that GO and BCL-2 inhibitors initiate double strand breaks in DNA, which trigger apoptosis and therefore, also improve the overall survival of AML patients (3). He also discussed the impact of some of these therapeutics on remission- specifically, IDH1/2 inhibitors are successful in reducing serum levels of 2-Hydroxyglutarate, which consequently increases the rate of complete remission in patients (3). Interestingly, Dr. Richard-Carpentier also indicated that the synergistic activity of cytarabine and daunorubicin in CPX-351 is beneficial in patients with secondary AML (3). However, while all these drugs have shown to benefit patient prognosis, Dr. Richard-Carpentier indicated the lengthy regulation process for targeted therapeutics and the high cost of these drugs; therefore, more research should be conducted to increase the feasibility of implementing targeted AML treatments, in order to further benefit patient care.
In the post-round discussion, Dr. Richard-Carpentier highlighted the value in conducting more research regarding AML in order to further enhance the care of patients. More research should be conducted to develop effective predictive and prognostic biomarkers in order to determine the response of novel therapeutics and patient outcome, respectively. Similarly, developing appropriate biomarkers to accurately determine the risk of relapse and resistance in AML patients will help physicians identify the best treatment approach for their patients. Moreover, there is also a growing need to develop even more targeted treatments for AML patients, in order to minimize off-target effects.
Furthermore, Dr. Richard-Carpentier also discussed the potential of a recently launched data-driven methodology (4). Specifically, Dr. Richard-Carpentier explained the potential benefit of physicians compiling pediatric AML patient data into a user-friendly database, in order to compare and contrast medical histories, genetic characteristics, and clinical presentations of these patients (4). Ultimately, understanding the mutations underpinning every AML diagnosis and working to achieve the highest cure rate should become priorities in the care of AML patients and in the practice of translational medicine.
Dr. Richard-Carpentier highly values his connections with patients and ensures to always keep their best interest at heart. His strong passion for science and love for engaging with people led him to pursue a career in medicine. The ability to become very knowledgeable in a range of human systems attracted him to complete an internal medicine residency. Similarly, the diversity in patient specific treatments sparked his interest to complete a subspecialty in hematology. Ultimately, Dr. Richard-Carpentier is a proud member of Queen’s University- he admires the close-knit community the institution offers its faculty and the countless opportunities it provides for collaborations and connections.
It was truly a pleasure to hear Dr. Richard Carpentier’s presentation on the exciting new therapeutics for AML and the power of precision medicine. On behalf of the TMED graduate program, I would like to thank him for his time and for his invaluable insight.
- Saultz J, Garzon R. Acute Myeloid Leukemia: A Concise Review. J Clin Med [Internet]. 2016 Mar 5 [cited 2020 Nov 8];5(3):33. Available from: https://pubmed.ncbi.nlm.nih.gov/26959069/
- Lai C, Doucette K, Norsworthy K. Recent drug approvals for acute myeloid leukemia [Internet]. Vol. 12, Journal of Hematology and Oncology. BioMed Central Ltd.; 2019 [cited 2020 Nov 6]. p. 100. Available from: https://jhoonline.biomedcentral.com/articles/10.1186/s13045-019-0774-x
- Watts J, Nimer S. Recent advances in the understanding and treatment of acute myeloid leukemia [Internet]. Vol. 7, F1000Research. F1000 Research Ltd; 2018 [cited 2020 Nov 8]. p. 1196. Available from: https://doi.org/10.12688/f1000research.14116.1
- Accenture debuts data-driven methodology for pediatric AML - MM&M - Medical Marketing and Media [Internet]. [cited 2020 Nov 8]. Available from: https://www.mmm-online.com/home/channel/accenture-debuts-data-driven-methodology-for-pediatric-aml/