a new hope for patients who do not respond to therapies – Repubblica.it

It is still an experimental therapy and its efficacy has been proven in studies that for now want to understand what is the right dose of medication to give to patients, but the results are so encouraging as to be presented in plenary session at the congress of the American Society of Hematology (Ash) in progress these days in Orlando. We are talking about a new monoclonal antibody, mosunetuzumab, given to patients with resistant non-Hodgkin's lymphoma, which means that it does not respond to any of the available therapies or that it does not do it anymore although it has been treated with different drugs, including CAR-T therapy. The international multicenter study presented in Orlando shows that in 22% of these difficult patients, mosunetuzumab led to complete remission of the disease.Non-Hodgkin's lymphomas are cancers of the lymphatic system and about 85% of the forms affect B cells, such as diffuse large B-cell lymphoma or follicular lymphoma. Most patients respond well to available chemotherapy, but those who do not have lasting results tend not to react well even to subsequent therapies. Recently, with the introduction of therapies based on engineered lymphocytes – CAR-T – it was possible to induce a response in 40% of some of these patients (CAR-T is approved for diffuse large B-cell lymphoma but not for follicular lymphoma). "There is therefore still a great need for treatments for cases of refractory or relapsed lymphoma, also because most patients are in too precarious health conditions to undergo CAR-T," explained Stephen J. Schuster, director of the Lymphoma Program of the Abramson Cancer Center at the University of Pennsylvania lead author of the study. "One of the benefits of this new drug is that it is available to everyone, ie it does not have to be produced for every single patient."
Mosunetuzumab is a monoclonal antibody designed to bind to two specific receptors of tumor cells: CD19, as do the "armed" T lymphocytes in CAR-T therapy, and CD20. To date over 270 patients have received the drug – in the form of infusions that last several months – in 7 countries around the world, of which 193 are evaluable results. The results show that in patients with aggressive disease, accounting for 65% of the sample, there was a reduction in the disease in 37% of cases and complete remission in 19%; in patients with more indolent disease, on the other hand, the reduction occurred in 63% of cases and complete remission in 43%. Not only. Remission lasts over time, after 6 months 83% of the indolent patients who had reached it and 71% of those with aggressive disease are still disease-free. And yet, in some of the patients previously treated with CAR-T, molecular tests showed that the engineered cells infused into their bodies increased following the administration of mosunetuzumab. "This means that not only mosunetuzumab is capable of killing cancer cells but also manages to revitalize CAR-T cells and increase the effectiveness of previous treatment," Schuster pointed out.It remains to be seen when during the treatment it is appropriate to also include this new molecule and especially if the risk of side effects typical of cellular therapies, such as cytokine release syndrome, is not increased too much in this way. In any case, the authors conclude, these are preliminary results that must be further confirmed by more advanced phase studies.