Epigenetic test could help predict effectiveness of immunotherapy in multiple myeloma

Multiple myeloma is a type of blood cancer that mainly appears after age 60. Its incidence therefore increases with the aging of the population. In this pathology, the bone marrow, the porous structure of bones that produces normal blood cells, is invaded by a proliferation of what are called plasma cells. These cells, which in healthy conditions are part of the immune system and help prevent infections, have transformed and, in addition to destroying the bone marrow, end up escaping and causing lesions in other places such as the spine vertebral, skull, pelvis and ribs. .

Current treatments can control the disease, even for a fairly long period, but there is no definitive cure yet. With the development of new generations of immunotherapy, using either antibodies or whole immune cells engineered to act as drugs, a new window of opportunity presents itself to treat patients who relapse or are refractory to standard therapy.

An article published in the journal Leukemia shows how an epigenetic test could determine the effectiveness of new immunotherapy treatments against multiple myeloma.

The research was led by Dr. Manel Esteller, ICREA Research Professor at the Josep Carreras Leukemia Research Institute (IJC) and Chairman of the Department of Genetics at the University of Barcelona School of Medicine, co-led by Dr. Gerardo Ferrer and first written by Laura Martínez-Verbo from the same center.

“We started looking for genes altered in cancer related to the immune system and how antigens are recognized to trigger a response from our defenses,” explains Dr. Esteller, setting out the framework of their research. This approach led to the identification of a subgroup of multiple myeloma patients with epigenetic alteration of the PVR gene, a key regulator of the immune system, leading to loss of its activity.

Dr. Esteller notes that “it was curious to observe that people with this defect had a better course of their disease, so we thought that the cancer cells from these individuals, who had a good clinical course, might be more easily attacked by the immune system. system.”

To test their hypothesis, the team used a cellular model for multiple myeloma and knocked out the PVR gene, to see how they responded to different forms of immunotherapy: single antibodies, T cells and genetically engineered natural killer cells ( CAR-T cells). In all cases, the immune response was effective against the tumor cells in vitro.

With this new information, clinicians could know in advance which patients would benefit most from immunotherapy, making their clinical management easier. And, beyond that, Dr. Esteller says: “Our results demonstrate that in this malignant blood disease, inhibition of the PVR gene decisively increases the probability of success of immunotherapy. It would now be the turn of the pharmaceutical industry and clinical research. to bring these results to the patient’s bedside.”