A new type of cell therapy is shown in a study published in “The New England Journal of Medicine” to prolong progression-free survival compared to standard therapies, 14 months versus 4 months, in patients with relapsed multiple myeloma and refractory who had received prior treatment.
The treatment – a new type of cell therapy – consists of extracting immune cells from the patient himself that will later be modified, in order to train them to recognize myeloma cells and thus be able to eliminate them. The cells extracted from the patient are lymphocytes (immune system cells) that are manipulated in the laboratory so that the lymphocytes express on their surface a chimeric receptor that enables them to recognize the antigen expressed by the myeloma cell, the BCMA antigen.
For José María Moraleda, head of the Hematology Service at Hospital de la Arrixaca in Murcia, the study is “very relevant because it represents a paradigm shift in the treatment of myeloma.” This former president of the Spanish Society of Hematology emphasizes that although already known, “the results confirm the potential of these cell therapies”, He also anticipates that during the European Congress of CAR-T in Rotterdam, from where he attends ABC Salud, “already more advanced CAR-T data is being presented with good results.”
Research with this new type of cell therapy -T-Cart lymphocytes- has been carried out in almost 20 national and international centers in 13 different countries, with the Clínica Universidad de Navarra being the one that has recruited the most patients.
When the lymphocytes manage to express this receptor, they are infused into the patient. In advance, the patient receives a short cycle of preparatory chemotherapy for the adequate reception of the modified lymphocytes. “Once the cell preparation is infused into the patient, the modified lymphocytes will recognize all the cells that express the BCMA antigen, which are myeloma cells, and will eliminate them,” says the hematologist.
“Although this CART therapy is approved in patients with advanced-stage myeloma, this study is the first to look at its efficacy in people who have suffered a relapse after having been treated with at least two prior therapies,” explains Paula Rodríguez, first trial signer.
In fact, Moraleda points out, some trials are showing the potential of these therapies in earlier phaseseven in the first line, where it competes in efficacy with standard therapy, such as bone marrow transplantation.
The objective of this study, in which the Spanish center began to participate in 2018, is to compare the efficacy of the drug ide-cel (CART therapy directed against BCMA) against different conventional treatments for myeloma.
“To do this, patients have been randomized between the two treatment arms, CAR therapy or standard treatment, with the advantage that patients assigned to the control arm could receive CART therapy at the time of progression,” explains the specialist-, which contributes a greater degree of scientific evidence to the result”.
This study is the first to look at its efficacy in people who have relapsed after being treated with at least two prior therapies.
Paula Rodriguez
University of Navarra Clinic
The median progression-free survival observed with CART therapy exceeds 13 months, while that observed with conventional treatment is less than 4 months.
These results, emphasizes Rodríguez Otero, “rsupport the role of CART therapy in patients with relapsed myeloma who have received at least two prior therapies. In this stage of the disease, therapeutic options are limited and suboptimal, therefore, in light of the results of this study, CART therapy could considerably improve the situation of these patients.”
Multiple myeloma is the third most frequent haematological tumor, since it represents 1% of all malignancies and 10% of haematological malignancies. It is a cancer of plasma cells, located in the bone marrow, whose role is crucial in the immune system. “Despite the important advances in treatment, most patients relapse and end up being resistant to the most important drugs available to date,” says Rodríguez Otero.
We have to have CAR-Ts that are faster, better, more powerful and last longer.
Jose Maria Moraleda
Head of the Hematology Service of the Hospital de la Arrixaca
In this situation, new treatments with different mechanisms of action are necessary, such as CAR T cell therapy. “This is a therapy that is showing a very beneficial effect for treating hematological tumors in our patients,” he adds. Philip Prosper, Director of the Cell Therapy Area of the University of Navarra Clinic.
Now, Moraleda qualifies, “with the CAR-T you also relapse.” He explains that what happens is that cell therapy ceases to be effective because the transfused cells are no longer alive or because the tumor cells have learned to hide the target to which this treatment is directed.
For this reason, he assures, “we have to continue improving. We have to have CAR-Ts that are faster, better, more powerful and last longer.”
Because, he adds, “the ultimate goal is to cure myeloma.”