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biomarkers

Denise Brock

Lung Cancer Video Library – Spanish Language: Video #28 Biomarkers for Predicting Activity of Immune Checkpoint Inhibitors

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GRACE Cancer Video Library - Lung

 

We continue to provide informational videos for our Spanish speaking community and welcome Dr. Luis Raez, MD FACP FCCP, Chief of Hematology/Oncology and Medical Director at Memorial Cancer Institute, and Clinical Associate Professor of Medicine at Florida International University.  Dr. Raez joined GRACE to discuss the basics of lung cancer.  In this 28th video for the Spanish lung cancer video library, Dr. Raez discusses biomarkers for predicting activity of immune checkpoint inhibitors.


 

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TRANSCRIPTS – Spanish and English
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Biomarcadores para predecir la actividad de los inhibidores inmunológicos de los puntos de control

Biological markers for the immunological checkpoint inhibitors activity

 

 Dr. Luis Raez, MD FACP FCCP,

Chief of Hematology/Oncology and Medical Director, Memorial Cancer Institute,

Clinical Associate Professor of Medicine, Florida International University


 

Spanish TRANSCRIPT

Mucha gente quiere saber hoy en día, cual es el marcador para los inhibidores de los puntos de control en la inmunoterapia. Como ustedes saben, esa es una discusión fluida que ya lleva muchos años y todavía lamentablemente no hay solución. Hasta hoy en día, hay agentes terapéuticos que están aprobados como nivolumab que son aprobados sin marcador y también hay agentes como pembrolizumab que están aprobados para pacientes que tienen el PDL1 positivo.

El problema, como ustedes saben, es que el marcador PDL no es muy exacto por muchas razones.

Primero porque la tecnología que usamos, probablemente no es suficiente. Para darles un ejemplo a veces en la misma muestra del paciente si analizamos tres partes diferentes de la muestra, la respuesta del PDL1 es diferente en las tres partes, y estamos hablando del mismo tipo de muestra. Si comparamos un paciente con metástasis de cerebro, el tumor originario del pulmón y una metástasis de otra parte del cuerpo, a pesar de ser el mismo paciente y del mismo tumor con diferentes localizaciones, la expresión del PDL1 es diferente. Entonces, no puede ser tan inexacto porque no nos ayuda para poder definir que pacientes van a recibir inmunoterapia y cuáles no.

Por esa razón, hay varias opciones: una opción es el proyecto Blueprint, en el que está incluso involucrado la FDA y toda la industria, en donde estamos tratando de comparar los diversos anticuerpos que usamos para PDL1. Como ustedes saben, hay anticuerpos DACO que usa Bristol-Myers y Merck, hay anticuerpos ventana que usan Roche y otras compañías. Todo esto se está estudiando en un consenso.

Otra opción es olvidarnos de PDL1 y buscamos otras formas de tratar de predecir la respuesta inmune. Por ejemplo, en el último ASCO, tenemos un poster de Foundation Medicine en el cual algunos de nosotros hemos puesto pacientes y estamos tratando de definir como darles inmunoterapia a los pacientes y hemos encontrado que cuando los pacientes tienen un número grande de mutaciones, les va mejor con quimioterapia. En el caso particular del poster que presentamos en ASCO en donde los pacientes que tiene más de 15 mutaciones en su reporte de tumor, probablemente le va a ir mejor con quimioterapia que si tiene menos de 15 mutaciones. A eso le llamamos carga tumoral, nosotros no somos los únicos, hay mucha gente que piensan que cuando la carga tumoral es mayor, es más antigénico y el paciente tiene más chance de responder a inmunoterapia.

Otra forma de conseguir quien responde mejor a quimioterapia es el efecto abspocal en donde los pacientes que reciben radiación, probablemente la destrucción de tejidos hace que ese tumor sea más inmunogénico entonces los pacientes pueden responder a inmunoterapia.

Otra forma de ver quien responde a quimioterapia, en el cancer de colón, estos pacientes que tienen estos defectos de replicación del DNA (microsatellite instability). Cuando estos pacientes tienen muchos de estos defectos de replicación del DNA y se les crea el microsatellite instability, les va muy bien con inmunoterapia en cancer de colon. Pero ahora, esto también se ha descrito en otros tumores, entonces queda un chance que en cancer de pulmón también puede ser otra alternativa.

Como ustedes ven, todavía no tenemos un marcador para inmunoterapia, pero seguimos activamente buscando una respuesta para saber que pacientes se van a beneficiar de la inmunoterapia y que pacientes no.


 

English TRANSCRIPT

Many people want to know, which one is the marker for immunotherapy checkpoint inhibitors. As you know, this is a good discussion that has been here for many years and we don’t have a solution yet. Nowadays, there are therapeutically agents that are approved without a marker like nivolumab and other approved for PDL1 positive patients like pembrolizumab.

The problem, as you know, is that the PDL marker is no very exact for many reasons.

First of all, the technology we use is not enough. For example, sometimes if we analyzed the patient’s sample in three different parts, we will get a different response of PDL1 in the three parts and we are talking of the same sample. If we compare a patient with brain metastasis, the original lung tumor and another body metastasis, despite being the same patient, the tumor will have a different PDL1 expression in each location. So, we cannot be inaccurate because that doesn’t help us define which patients will get immunotherapy and which ones will not.

For that reason, there are many options: one is the Blueprint project, where the FDA in involved too, where we are trying to compare diverse antibodies for PDL1. As you know, there are DACO antibodies that are used by Myers and Merck, and there are window antibodies used by Roche and other companies. All of these is being studied in a consensus.

Another option is forgetting PDL1 and search for other ways to predict the immune response. For example, in the last ASCO we had a poster in the Foundation Medicine in which some of us have posted patients trying to define how to give them immunotherapy. We have found that patients with more mutations, go better with chemotherapy than those patients with less than 15 mutations. We call these, the tumoral load, and we are not the only ones doing it, because there are some people that think that the bigger the tumoral load, there is a greater chance of responding to chemotherapy. 

Other method to see who responds to chemotherapy is the abspocal effect where in patients who receive radiation, destruction of the tissues will make the tumor more immunological and then they will respond better to immunotherapy.

Another way of seeing who responds to chemotherapy, is for example in colon cancer where these patients have microsatellite instability. When these patients have these DNA replication defects, they get microsatellite instability and they will usually respond well to immunotherapy. But now it has also been described to other tumors, so we have a chance that it can also work in lung cancer.

As you can see, we don’t have a marker for immunotherapy yet, but we are still actively searching for a response to know which patients will benefit from immunotherapy and which will not.


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Please feel free to offer comments and raise questions in our Discussion Forums.

 


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