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Dr. Richard-Carpentier

"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.

 

Reference List:

  1. 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/
  2. 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
  3. 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
  4. 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/

Comments

Name
Caitlyn Vlasschaert

Tue, 11/10/2020 - 13:36

It was both helpful & inspiring to hear from a newly established physician-scientist this past week. Dr. Richard-Carpentier succinctly presented several ongoing efforts in translational hematology-- from characterizing AML-causing mutations to developing (& re-purposing) drugs to target the disease. I particularly enjoyed learning about his transition to independent research and how his professional relationships within the Leucegene network (https://leucegene.ca/) have grown from mentorship to collaboration. The local medical & research community is certainly very lucky that Dr. Richard-Carpentier decided to set up shop at Queen's.

Thanks also to my colleague Melinda for leading the discussion ever so eloquently. Your communication skills are seriously impressive.

Name
Caitlyn Vlasschaert

Name
Melinda Chelva

Wed, 11/11/2020 - 09:18

In reply to by Caitlyn Vlasschaert (not verified)

Thank you so much for the kind compliment Caitlyn- I truly appreciate it, and for sharing the link to the Leucegene Project. I agree, Dr. Richard-Carpentier is definitely an inspiration to aspiring physician-scientists. Through his presentation, he clearly demonstrated how the practice of hematology has evolved in recent years and the large potential of a young physician-scientist. I'm looking forward to following Dr. Richard-Carpentier's research and the evolution of personalized medicine in the years to come.

Name
Melinda Chelva

Name
Jordan Harry

Wed, 11/11/2020 - 11:18

Thank you Melinda for an excellent discussion, and an incredible blog post. Additionally, a sincere thanks to Dr. Richard-Carpentier for his presentation and time.
Something that stuck out to me from this presentation and personal reading, is the concept of resistance. Resistance to broad spectrum therapy is a known problem, however, as we move towards personalized therapy, the concept of drug resistance is persisting. This is an incredibly important concept for researchers to pursue, because as Dr. Richard-Carpentier pointed out, we have many novel effective drugs. Resistance could impact the efficacy of these novel therapeutics. I am personally interested in current and future research related to the use of biomarkers to determine risk of relapse and drug resistance. I think that this would not only help determine the best treatment approach for patients, but would also allow clinicians to select appropriate effective therapies sooner.

Name
Jordan Harry

Thank you Jordan! You raise a very important point- I definitely think the next step in AML research is to focus on developing effective biomarkers to determine the resistance and relapse of these novel therapeutics. Researching this at the "bench-side" will help to further enhance patient care on the "bed-side"- gracefully depicting the essence of translational medicine.

Name
Melinda Chelva

Name
Jummy Oladipo

Wed, 11/11/2020 - 16:09

Thank you, Melinda for a comprehensive summary of the talk. Additionally, thank you Dr. Guillaume Richard-Carpentier for taking the time to speak with us. It was very inspiring to hear from a new faculty member here at Queen's. One thing that interested me during our discussion was the cost of these newly developed drugs that are showing great efficacy against AML. Dr. Richard-Carpentier elaborated on the challenges of having patients who are well-informed on the potential therapeutics available for treating their cancer, yet they may not be covered under their insurance. This dampens the translatability of these drugs into patient care by posing a large financial barrier. It was also interesting to hear the role that physicians play in advocating on the behalf of patients for the reduced pricing of drugs. While physicians may not have a direct influence through discussing with pharmaceutical companies, the successful outcomes of using these drugs in clinical settings may influence these companies to offset some of the costs. Thank you Dr. Guillaume Richard-Carpentier for your insight.

Name
Jummy Oladipo

Thank you Jummy! I agree- it is disheartening to know that the financial barrier that drug costs impose can ultimately inhibit patients from receiving the most effective treatment. I'm curious to learn more about whether there are patient groups that use social media as a platform to advocate for reducing the cost of these drugs, and if so, how successful they have been in persuading pharmaceutical companies? I also wonder whether the voices of patients resonate equally to these companies as those of physicians?

Name
Melinda Chelva

Name
Charmi Shah

Wed, 11/11/2020 - 23:44

It was inspiring to hear Dr. Richard-Carpentier speak at the Medical Grand Rounds. He was definitely able to offer a new perspective on this field being a newly appointed physician-scientist at Queens.

I found it interesting how Dr. Richard-Carpentier ensured to point out the difference between precision medicine and personalized medicine. Since precision medicine can help predict which treatments and prevention strategies would be best for a particular disease, it can aid in the design of multiple treatment options that target the disease from differing targets. This can lead to gaining the individualized care that is strived for in personalized medicine. I look forward to learning about the progress in AML treatments and following Dr. Richard-Carpentier’s research journey.

Thank you again Dr. Richard-Carpentier for your insight, and Melinda for the excellent facilitation and summary.

Name
Charmi Shah

Name
Melinda Chelva

Thu, 11/12/2020 - 10:40

In reply to by Charmi Shah (not verified)

Thank you Charmi! I also found this interesting! I am looking forward to following the literature to see how research in precision medicine advances in years to come- specifically, I am interested to see how its use will be extended to treat not only other types of cancers, but other diseases that display clinical and genetic heterogeneity.

Name
Melinda Chelva

Name
Max Moloney

Thu, 11/12/2020 - 14:34

Thank you, Melinda, for your detailed summary of Dr. Richard-Carpentier’s presentation during Medical Grand Rounds last Thursday.

I was very intrigued by Dr. Richard-Carpentier’s work in precision medicine as it pertains to acute myeloid leukemia. I believe there is a great deal of potential in data-driven methodologies for precision medicine that has the potential to impact many fields of research. I look forward to following the progress and development of these data-driven methodologies in the future.

I would also like to thank Dr. Richard-Carpentier for his candid discussion on life as a young physician-scientist at Queen’s and to Melinda for her excellent facilitation of the question period. Dr. Richard-Carpentier was able to provide great advice for young researchers that I and many other students will take into consideration as we progress through our graduate programs.

Name
Max Moloney

Thank you Max! I agree, I am also looking forward to following the advancement of data-driven methodologies in the future. Considering that AML is often diagnosed in older individuals due to the accumulation of mutations over time, it is promising to know that data-driven methodologies have progressed enough to help determine the best treatment approach for paediatric patients (4). However, due to the diversity in genetic and clinical profiles of AML patients, these databases might not contain data for each unique variation of the disease that a patient may present with. Without this data, it may be difficult for physicians to determine the best treatment approach for their patients. I wonder whether this will be a limitation to the use of databases in AML treatment?

Name
Melinda Chelva

Name
Kassandra Coyle

Sun, 11/15/2020 - 20:38

Thank you, Dr. Richard-Carpentier for the insightful talk and thank you, Melinda, for your excellent summary! Like my fellow classmates, I was also very intrigued by the potential of precision medicine. Further reading led me to a recent study demonstrating the success of precision medicine in treating AML. In this study, patients were enrolled in a clinical trial that aimed to provide cytogenic and mutational data, prior to treatment selection. It was found that the thirty-day mortality was less frequent and overall survival was significantly longer for patients who underwent the treatment suggested by the study as opposed to those who elected standard of care treatments. This study highlights the benefits that precision medicine can have. I look forward to continuing to follow the advancements in this field and am very optimistic about the future of precision medicine.

Burd, A. et al. Precision medicine treatment in acute myeloid leukemia using prospective genomic profiling: feasibility and preliminary efficacy of the Beat AML Master Trial. Nat. Med. (2020). doi:10.1038/s41591-020-1089-8

Name
Kassandra Coyle

Name
Melinda Chelva

Mon, 11/16/2020 - 10:38

In reply to by Anonymous (not verified)

Thank you for sharing this article Kassandra- it contains very interesting and promising results! I noticed that only patients older than 60 were recruited to participate in the Beat AML Master Trial; I wonder whether other recent trials have also evaluated the thirty-day mortality endpoint in paediatric patients, and whether similar results have been noted in this cohort?
I also recently stumbled upon PedAL, which is a global precision medicine master clinic through the Leukemia and Lymphoma Society (https://www.lls.org/childrens-initiative/pedal). This initiative began in 2019 with the testing of multiple targeted therapies. Overall, the initiative acknowledges that progress for treatment of children has always lagged behind that of adults; therefore, they aim to extend the power of precision medicine to the paediatric population and ultimately, change how children with acute leukemia are treated.

Name
Melinda Chelva

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