A "catalog" of multiple myeloma cases to improve their treatment

Multiple myeloma is a blood cancer that occurs in the bone marrow. It occurs due to the proliferation of plasma cells, a type of immune cells responsible for producing antibodies. It is a heterogeneous disease, which means that it can manifest itself in different ways and have different responses to treatments.

To meet the medical need for new treatments to cure the disease, an international group of researchers, led by Dr. José Ángel Martínez-Climent at the CIMA (Centro de Investigación Médica Aplicada) of the University of Navarra in Spain, has used genetic engineering technologies and multiomic analysis at the cellular and molecular level.

With this advanced technology, they have been able to characterize more than 500 genetically heterogeneous mice that develop multiple myeloma, and samples from more than 1,000 patients with this disease, treated in the Hematological Cancer Area of ​​the Clínica Universidad de Navarra cancer center.

Thanks to this analysis, it has been possible to generate models that accurately reflect key aspects of the origin and development of human multiple myeloma. This makes it possible to study the progression of the disease, test therapeutic alternatives and predict the response to combinations of immunotherapeutic drugs in the clinic, as pointed out by Marta Larráyoz, researcher at the CIMA Hemato-Oncology Program and co-author of the study.

Main implications for patients

Advancing work in the laboratory requires being able to compare and validate the information provided by preclinical models with patient data. Thanks to the continuous collaboration of the researchers with the hematologists of the oncology center of the Clínica Universidad de Navarra, it has been possible to identify a correlation between the genetic and immunological features of each tumor and its selective response to multiple myeloma in mouse models. preclinical therapies, as explained by José Ángel Martínez-Climent, principal investigator and coordinator of the study, also belonging to the CIMA Hemato-Oncology Program.

This line of research will allow specialists to anticipate the outcome of treatment with next-generation immunotherapies and imitate in the laboratory clinical situations associated with the worst results, such as high-risk multiple myeloma, extramedullary disease or acquired therapeutic resistance. “This scenario offers us opportunities to advance in the investigation of new therapeutic strategies and to optimize the design of future immunotherapy clinical trials,” says Martínez-Climent. In addition, “we are testing novel therapies in experimental models at stages of the disease where multiple myeloma cells might be most vulnerable, particularly in early precursor conditions or in the minimal residual disease state (after treatment, when few cells remain). tumors). To do this, we have established numerous scientific collaborations with pharmaceutical companies that are developing clinical trials in this disease to carry out these same trials in our mice”.

The ultimate goal, the researchers say, “is to transfer the discoveries from the laboratory to the clinic so that research initiatives such as ours can be extrapolated to other hematological malignancies and solid tumors that remain incurable with currently available treatments.”

Researchers from CIMA and the oncology center of the Clínica Universidad de Navarra. In front: Teresa Lozano, Maddalen Jiménez, Jon Celay, Marta Larráyoz, José Ángel Martínez Climent, María José García Barchino and Amaia Etxebeste. Behind: Juan José Lasarte, Vicente Fresquet, Sergio Roa, Cristina Pérez, Pablo sarobe, Felipe Prósper, Bruno Paiva, Jesús San Miguel and Xabier Agirre. (Photo: University of Navarra)

The following entities on the Spanish side have worked on the study: Clínica Universidad de Navarra, Severo Ochoa Center for Molecular Biology, National Center for Oncological Research, Navarrabiomed. On the US side: Mayo Clinic, Yale University, Dana-Farber Cancer Institute at Harvard University, Cornell University and the biotech company Genentech. On the Swiss side: the Innovation Center of the pharmaceutical company Roche. And for the Japanese side: University of Tsukuba.

The study is titled “Preclinical models for prediction of immunotherapy outcomes and immune evasion mechanisms in genetically heterogeneous multiple myeloma”. And it has been published in the academic journal Nature Medicine. (Source: University of Navarra)