Taking the leap to transform leukemia treatment

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I’m thrilled to be starting this year’s ‘In My Blood’ interview series with my new colleague, Bruno Medeiros, Global Head of Leukemia Clinical Development and Strategy, 阿斯利康 . Bruno brings a wealth of experience from his long-standing role at Stanford, where he served as an associate professor of medicine and led multiple clinical trials focused on the development of novel therapeutic regimens for patients with acute leukemia.

Thank you for joining me, Bruno. I’m very impressed by your career and eager to learn more about your background. What attracted you to industry and who inspired your career path?

Given the space we work in, there are often opportunities to step over from academia to industry. I had a number of colleagues who transitioned across, and one day, my curiosity, and the right opportunity, compelled me to make the move myself.

My career inspiration stems from multiple sources. Initially, it came from my dad working as a hematologist. Then as I began to develop my career, I looked to Elihu Estey, an exemplary scholar in hematology and pioneer in acute myeloid leukemia research, as someone I respected significantly. Reflecting on my time at Stanford, my colleague Steven Contre, who was a remarkable investigator and dedicated hematologist, influenced my academic career greatly, as well as how I functioned as both a physician and a clinical trialist.?

Some inspiring individuals, for sure. So, now in your new role as Global Head of Leukemia Strategy, what do you think are some of the key challenges and unmet medical needs to address in leukemia treatments?

In addition to being a good leader and role model to my team, my ultimate goal in my new role is to get novel therapies into the clinic so that, eventually, more patients can access the benefits they could offer. However, there are some significant challenges we must overcome to achieve this goal.

Unlike some hematological cancers, where the cure or survival rates have significantly improved over the last couple of decades, there remains high unmet need in acute leukemia.1,2 In particular, patients who have relapsed, become refractory, developed secondary cancers or have high-risk disease, have very poor outcomes currently.2 A lot more can be done for these patients.

A major hurdle is the heterogeneity of these diseases.3 For example, we think about myeloid leukemia as a single entity, when genomically, we know it could represent up to 15 different leukemia subtypes, each with unique characteristics.4,5 With so much diversity and relatively small patient populations, it makes designing novel drugs very complicated.3 Another significant hurdle is the shared expression of surface markers in normal and malignant cells, which makes the on-target, off-tumor toxicities, especially in myeloid malignancies, particularly challenging.6

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Which scientific advances and innovations are you most excited about that may hold promise for overcoming some of the challenges in leukemia that you mentioned?

Immune-mediated treatment modalities, such as T-cell engagers or chimeric antigen receptor (CAR)-T cells, have been revolutionary for some areas of hematology, and I believe this is just the tip of the iceberg.7 I think they have potential for the treatment of acute leukemias, as they are doing in other hematologic malignancies.7 But there are still some major hurdles to overcome.

In the current treatment landscape for myeloid malignancies, we have not been able to preferentially target the cancerous cells with CAR-Ts, while sparing the normal cells.8 I think technology is advancing in such a way that we can introduce other manipulations, beyond CAR-Ts, to address this. This could potentially optimize the effect of and the safety profile of immune-based therapies for the treatment of acute myeloid leukemia.

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In three words, can you describe your impression of working at AstraZeneca so far?

I can’t think of only three words! I’ll give you three partially hyphenated words because I think they’re reflective of my impressions. First is scientifically-rigorous, the second is laser-focused and the third is ambitious. I think these best describe the hematology franchise and the company.

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And the final question that I ask everyone in these interviews…what's something on your bucket list unrelated to work?

I grew up in Brazil watching Formula One on Sunday mornings and have maintained a love for the sport even after moving abroad. So, at the top of my bucket list, I would go to Monte Carlo to watch the Monaco Grand Prix in person.

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References:

1.?????? Malalur P, Agastya M, Wahi-Guruaj S, et al. Cancer survivorship in hematologic malignancies: Lifestyle changes after diagnosis. Cancer Med. 2021;10(3):1066-1073.

2.?????? Thol F, Heuser M. Treatment for Relapsed/Refractory Acute Myeloid Leukemia. Hemasphere. 2021;5(6):e572.

3.?????? Liu J, Jiang P, Lu Z, et al. Decoding Leukemia at the single-cell level: clonal architecture, classification, microenvironment, and drug resistance. Exp Hematol Oncol. 2024;13(12).

4.?????? American Cancer Society. Acute Myeloid Leukemia (AML) Subtypes and Prognostic Factors. https://www.cancer.org/cancer/types/acute-myeloid-leukemia/detection-diagnosis-staging/how-classified.html. Accessed March 5, 2024.

5.?????? The Leukemia & Lymphoma Society. CMML Subtypes. https://www.lls.org/leukemia/chronic-myelomonocytic-leukemia/diagnosis/cmml-subtypes. Accessed March 5, 2024.

6.?????? Foon AK, Schroff RW, Gale RP. Surface Markers on Leukemia and Lymphoma Cells: Recent Advances. Blood. 1982;1(1):1-19.

7.?????? Noh J, Seo H, Lee J, et al. Immunotherapy in Hematologic Malignancies: Emerging Therapies and Novel Approaches. Int J Mol Sci. 2020;21(21):8000.

8.?????? Mardiana S, Gill S. CAR T Cells for Acute Myeloid Leukemia: State of the Art and Future Directions. Front. Oncol. 2020;10.