They also call it the “seed and soil disease”. Because in multiple myeloma, a malignant blood tumor in which plasma cells proliferate uncontrollably and accumulate in the bone marrow, one of the keystones of the disease is represented by the interaction between neoplastic cells and those of the medullary microenvironment, which nourish them and they oxygenate them allowing them to replicate. And it is therefore also by acting on this collaboration that the tumor can be beaten: “The new drugs have this goal: they interrupt the exchange between malignant cells and those of the microenvironment”, he explains Michele Cavo, hematologist of the Department of Specialized, Diagnostic and Experimental Medicine of the University of Bologna and director of the School of Specialization in Hematology of the same university. If the soil does not feed the seed, the seed does not sprout. It is thanks to this intuition that the treatment of multiple myeloma in the last 20 years has changed its face: no longer a disease with an almost always fatal outcome, but a tumor that can be chronic for a long time, first thanks to immunomodulating drugs, then to inhibitors of the proteasome and finally to monoclonal antibodies.
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Belantamab mafodotin is also part of the latter class, now also available in Italy. Technically it is a ‘conjugated’ monoclonal antibody, that is, composed of two molecules: a humanized monoclonal antibody (belantamab) and a chemotherapy (mafodotin). The first is capable of detecting a leak on the surface of the tumor cell, a receptor expressed on the surface of myeloma plasma cells, called BCMA (B cell maturation antigen). Once bound to the cell surface, belantamab penetrates cells and deposits cytotoxin, the chemotherapy that blocks their vital processes and causes their death, minimizing damage to healthy tissues. “A double action drug then – continues Cavo – a classic, immunotherapy, to which is added that of the toxin”.
Who is the new therapy for
A very particular category of patients will benefit from this new weapon against multiple myeloma: those who – he explains Sergio Amadori, president of AIL– have been subjected to at least four previous therapies with other drugs, with relapses or refractoriness, for which there are no other therapeutic solutions and therefore intended for palliation. There are currently about 200 patients each year in Italy. But it is quite evident that the story of this drug does not end there. “First of all, belantamab is today a bridge that allows us to offer the most difficult patients an additional weapon against cancer and give us time to ferry them to the other shore, waiting for the Car-T train to pass”, he continues. the hematologist, or one of the most promising immunotherapy strategies capable of making a change in the treatment of blood cancers. But, adds Cavo, there are already studies underway that are evaluating this conjugated monoclonal antibody in combination with other agents, both standard and immunomodulatory drugs.
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And the next step will then be to verify the administration of belantamab mafodotin in increasingly early stages of the disease, up to the treatment of the patient with newly diagnosed multiple myeloma. To verify the safety and efficacy of the new drug was the DREAMM-2 study, published on The Lancet Oncology, according to which more than half of the patients (58%) achieved a very good or superior and in some cases complete partial response, while the median overall survival was approximately 14 months, a surprising result in a patient population who, as mentioned, he has a form of disease for which the available drugs have lost efficacy.
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