13 minute read
Immunotherapy as the new paradigm in the treatment of cancer
Interview with Dr. José Manuel Celaya Velázquez, Medical Director of Bristol Myers Squibb México
According to UN reports, in 2021 there were more than 10 million deaths globally due to cancer (1). It is striking that, although this condition is treatable in all its types, in addition to being preventable and curable in most cases, cancer is still one of the leading causes of death in the world.
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More than ten years ago and in this same context, the pharmaceutical Bristol Myers Squibb formed the International Immuno-Oncology Network (II-ON), one of the first global collaborations to unite industry and academia with the intention of promoting the scientific understanding of IoT (2).
In coherence with the work carried out by the pharmaceutical company, we find the collaboration of Dr. José Manuel Celaya Velázquez, Medical Director of Bristol Myers Squibb Mexico, whom we thank for granting this interview to talk a little more about new cancer treatments.
Dear Dr. Celaya, could you tell us what are the transformational therapies you have developed for patients with serious diseases such as cancer?
Regarding cancer, we have had a very important development and evolution, because we are pioneers in immunotherapy or immuno-oncology, as it is also known, which are a class of drugs that use the immune system itself to attack the tumor. Ten years ago, we managed to introduce the first immunotherapy to the Mexican market. Its development has been a great experience because during that time it has helped 30% of patients with the disease, even in the advanced/metastatic stage (which has spread to other parts of the body), to be alive in the long term.
Although for some it could be a conservative figure, the number of patients who benefit from this type of treatment is significant, especially if one considers that, for example, in Mexico, every year more than 195 thousand people receive a diagnosis with this type of cancer.
There is also cell therapy called CAR-T (chimeric antigen receptor T cell therapies), which is a therapeutic innovation in which the patient has blood drawn by selecting their T lymphocytes (a type of white blood cell). Once these lymphocytes have been modified by the laboratory with a newly inserted receptor that identifies and destroys cancer cells, it is infused back into the person as a cellular drug.
Why is immunotherapy called the new paradigm in cancer treatment?
The concept of immunotherapy is very interesting, with it we are getting to what we see in science fiction movies, where the immune system itself is the one that attacks the tumor. We are returning the body to its natural state in such a way that it identifies which cells should not be there and eliminates them. Let’s talk first about what immunity is: it is the system that allows us to defend ourselves against what is not our own. Their main function is to destroy invading agents: viruses, bacteria, fungi, and parasites. However, sometimes this becomes a lethal risk for its owner.
The intention of the immune system is to identify these cells when they are still a small number, or when they are still initiating a transformation and that they are not entirely malignant; It identifies them, attacks them, and eliminates them, this is called immunoediting. It is a concept that we could say is recent, but now in oncology, it has been seen that it has a very important role.
Arthritis, lupus, type I diabetes, and fifty other autoimmune diseases are due to the patient’s immune system exceeding its functions and reac-ting against its own cells. And conversely, the immunodeficiencies that prevent us from infections and other diseases are due to the fact that the system has been pressing the brakes too much. Playing with this delicate balance, which we call immune checkpoints, is one of the most promising lines of research against cancer, which has made possible the development of so-called immunotherapies.
These are the result of research funded by Bristol Myers Squibb (BMS) in partnership with Dr. James P. Allison, executive director of the immunotherapy platform at the University of Texas MD Anderson Cancer Center, United States, and Dr. Tasuku Honjo, Kyoto University, Japan.
The work of both researchers focused on taking advantage of the immune system’s ability to identify and eliminate cancer cells, which is why they won the 2018 Nobel Prize in Physiology/ Medicine. His goal was to find a way to remove “the brakes” and “accelerate” a person’s own defense reactions. It is a new therapeutic reality that is proving useful in several types of tumors and from which a third of patients can benefit. In addition to having less toxicity, compared to traditional treatments, one of its main advantages lies in its very specific reaction according to the tumor being treated, unlike conventional therapies.
While surgery, radiation therapy, chemotherapy, or targeted therapies have been the mainstay of treatment for cancer diseases, long-term survival and good quality of life remain unattainable for many patients with advanced/metastatic disease. For many common tumors, 5-year survival rates remain low, so there is a need not met with the current standard of care.
Recent findings with therapies that use the body’s immune system to fight cancer (immuno-oncology therapies) have fueled hope, for the first time, that long-term survival and quality of life are possible for people with many forms of advanced cancer. These conventional therapies use tools outside the body and act directly on the tumor. Instead, I-O takes advantage of the immune system itself and activates its natural mechanisms to produce T cells that attack tumor cells from within, that is, in the same way that the body fights against other infections and diseases.
Although immunotherapy has been a revolution, the most recent data indicate that we should no longer speak of an individual treatment scheme, but in combination with other therapeutic options to improve the health outcomes of patients, in addition to the fact that it has also been shown that early detection and good training to the clinical team that administers them is key in the prognosis of recovery and cure.
Today, for example, we know that dual immunotherapy plus chemotherapy is emerging as the first-line treatment in patients with non-small cell lung cancer (NSCLC) (3), the most common form of lung cancer and whose main risk factor is smoking (4). Unfortunately, these types of tumors are usually diagnosed late; therefore, their management focuses mainly on advanced or metastatic stages. This therapeutic regimen has demonstrated clinically significant progress in overall survival (period from initiation of treatment to the last check-up) (5) and progression-free survival (time where the condition does not worsen from treatment) (6). With a complex disease such as NSCLC, which currently affects more than 7,000 Mexicans (7), the availability of different treatment options is critical for patients facing a difficult prognosis, hence access to innovative medicines is crucial.
There are also several lines of research open in this field with different highly effective immunotherapeutic combinations that can change the way melanoma is treated in the future, especially in an advanced stage with or without mutations in a specific gene called BRAF, which occurs in 50% of cases (8); or, in inoperable metastatic tumors by inhibiting the LAG-3 and PD-1 proteins that prevent the immune system from achieving an energetic response. against cancer cells (9).
Based on the medical advances seen so far, what do you consider to be the future of personalized oncology and what efforts does BMS make to better understand the biology of cancer?
I believe that fortunately, a panorama of possibilities opens up for cancer patients. Today, chemotherapy is still considered a therapeutic option, because there are tumors that require that through toxic substances the size of the tumor is reduced so that there can be a good surgery or a faster response. There are also what we call target therapies, target therapies, or target therapies, which are therapies that specifically identify a marker of a certain tumor. Let’s say I develop lung cancer that has a mutation, what this targeted therapy does is directly attack that mutation. We call that therapy target (like the targets of the Olympic Games) because it is specifically aimed at that mutation, and if that tumor in the lung has no mutation, the drug that I am going to give it will not be of any use, then these therapies are for certain specific tumors.
What is the future we hope for? We expect combinations of these therapies, but for this, there must be a good complete diagnosis so that I can offer you the best therapeutic option. And I think we’re also going to see more development towards resistance to certain tumors because, unfortunately, we see that there are also tumors that are resistant and that express other proteins, other mutational variants that don’t allow them to respond to these types of therapies, even with combinations, and that’s where research is going to go, to identify which tumors are those that could develop resistance to treat them from the beginning.
Today, we continue to seek therapies at the forefront of scientific innovation. For example, through the use of precision and translational medicine, which combines disciplines, resources, knowledge, and techniques, we are trying to identify at-risk populations and select the appropriate treatment for each, based on the biology of their disease; even potentially before they begin to show symptoms. This avoids the frustration of trying multiple therapies before finding the one that offers the best results and of course, greatly reduces the associated costs for health systems, governments, and patients.
Do you conduct any medical education programs to assist health professionals in therapeutic decisions with their patients?
1. We suggest highlighting the importance of medical education in a hybrid format
Talk, for example, about the importance of events such as Synergy, which BMS recently held in Mérida, Yucatán, to update the medical community on the use of innovative medicines and therapeutic schemes for different types of cancer that affect Mexicans, including renal, gastrointestinal, lung and melanoma tumors, and which also had the endorsement of the Mexican Council of Oncology, A.C, with nine points of recertification, which recognize the effort of health professionals.
2. Our Patient Support Program, which helps them improve the control of their health condition.
The prioritization of putting patients at the center of deverything we do reaffirms our commitment, and we will continue to foster and strengthen partnerships with key stakeholders, including governments, so that, through science and technology, we find joint solutions that contribute to improving the health of current and future generations.
• During the first month of the pandemic our R+D team could not access the institutions where the clinical trials were being carried out and this made us significantly change the way BMS operates.
• We decided to integrate the technology throughout the value chain.
• We strengthened our approach with medical professionals through digital tools and also changed our training programs to online modalities.
• Internally, we began to refine our data platforms and supply chains and offered all our employees the possibility to work remotely.
• The entire BMS team met this challenge with resilience, and we have learned to overcome crises as we grow and provide comprehensive solutions to our patients.
• Digitalization and collaborative work are definitely here to stay and will continue to be strategic pillars to continue promoting the company’s innovation.
Finally, Dr. Celaya, for your consideration, what are the achievements and advances that have had the greatest positive impact on the lives of your patients?
We are proud to have a history of scientific excellence, helping to transform the health outcomes of patients with serious diseases such as cancer. We have a great commitment to the research of new innovative therapies, so in the last 5 years, in BMS Mexico we have invested more than 60 million dollars in R&D, a figure that we plan to continue maintaining.
Today, we have more than 50 clinical studies in various therapeutic areas: oncology, immunology, cardiovascular, hematology, and fibrosis, where more than 300 patients are participating in 80 different research sites of the institutional and private environment around the country, being one of the few companies that have R&D teams in IMSS facilities for 10 years.
Mexico is the subsidiary that leads the most important project in breast cancer research protocols; Of 10 authors of the protocol, 3 are Mexican researchers.
Editorial Clinical Research Insider
Sources:
(2022), El cáncer afecta a todos igual, pero millones de personas mueren por la desigualdad de acceso al tratamiento. Retrieved September 19, 2022 from: https://news.un.org/ es/story/2022/02/1503572
(2020), Unidos para enfrentar el Cáncer. Retrieved September 19, 2022 from: https://www.bms.com/es/life-and-science/science/united-to-face-cancer.html
E-cancer. (2020). BMS anuncia la aprobación de la UE de la opción de tratamiento de primera línea para el cáncer de pulmón de células no pequeñas avanzado. August 31, 2022, from: Ecancer Medical Science Sitio web: https://ecancer.org/es/news/19042-bms-anuncia-la-aprobacion-de-la-ue-de-la-opcion-de-tratamiento-de-primera-linea-para-elcancer-de-pulmon-de-celulas-no-pequeas-avanzado.
Institutos Nacionales de Salud, Gobierno de Estados Unidos. (2022). Fumar es el factor de riesgo principal del cáncer de pulmón de células no pequeñas. August 31, 2022, from: Instituto Nacional del Cáncer Sitio web: https://www.cancer.gov/espanol/tipos/pulmon/paciente/tratamiento-pulmon-celulas-no-pequenas-pdq#_118
Clínica Universidad de Navarra, España. (2022). Diccionario médico: Supervivencia global. August 31, 2022, from: Universidad de Navarra Sitio web: https://www.cun.es/diccionariomedico/terminos/supervivencia-globa
Institutos Nacionales de Salud, Gobierno de Estados Unidos. (2022). Supervivencia sin progresión. August 31, 2022, from: Instituto Nacional del Cáncer Sitio web: https://www.cancer. gov/espanol/publicaciones/diccionarios/diccionario-cancer/def/supervivencia-sin-progresion
International Agency for Research on Cancer. (2021). México: Source Globocan 2020, Incidence, Mortality and Prevalence by cancer site. 3August 31, 2022, from: World Health Organization. Sitio web: https://gco.iarc.fr/today/data/factsheets/populations/484-mexico-fact-sheets.pdf.
Equipo de redactores y editores de la American Cancer Society (ACS). (2022). Medicamentos de terapia dirigida para el cáncer de piel tipo melanoma: Medicamentos que atacan a las células con cambios en el gen BRAF. August 31, 2022, from: ACS Sitio web: https://www.cancer.org/es/cancer/cancer-de-piel-tipo-melanoma/tratamiento/terapia-dirigida.html
Institutos Nacionales de Salud, Gobierno de Estados Unidos. (2022). La FDA aprobó Opdualag, la primera inmunoterapia dirigida a LAG-3. August 31, 2022, from: Instituto Nacional del Cáncer Sitio web: https://www.cancer.gov/espanol/noticias/temas-y-relatos-blog/2022/fda-aprueba-opdualag-melanoma-avanzado
