Home » Multiple myeloma, towards chronicization thanks to innovative therapies

Multiple myeloma, towards chronicization thanks to innovative therapies

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Despite being classified as a rare disease, multiple myeloma still accounts for 13% of blood cancers, especially in the age group between 65 and 70 years with important complications including pain and serious infections, which very often hinder access to care. Yet, research has not spared and today – thanks to innovative therapies such as immunomodulators, used in combination with other drugs – it is possible to significantly extend the time intervals free from relapse with a good quality of life, in many cases becoming chronic. the illness. In fact, in twenty years the median survival has gone from about 36 months to 7 years. The perspectives offered by the innovative weapons against multiple myeloma were explored in a virtual media tutorial, promoted by Celgene now part of Bristol Myers Squibb.

A disease that comes in old age

Every year, in Italy, 5,800 people are affected by multiple myeloma, a blood cancer that originates in the bone marrow. “Multiple myeloma is a typical disease of the elderly, in fact the average age at diagnosis is about 70 years – he says Michele Cavo, director of the Institute of Hematology ‘LA Seràgnoli’, Irccs S. Orsola-Malpighi, University of Bologna and full professor of Hematology at the same University. “In about one third of cases the disease can begin without symptoms, while in the remaining two thirds bone pain associated with skeletal disease are the most common symptoms.”

From chemotherapy to immunomodulators

The therapy was based for many decades on the administration of chemotherapy, with the possible addition of radiotherapy, but the results obtained were modest, due to the high resistance of lymphocytes and plasma cells to treatments. “The therapeutic innovation in the last 20 years – continues Cavo – has been represented by the introduction of drugs with direct action towards plasma cells and the ‘medullary microenvironment’, first of all immunomodulators”. The latter have radically changed the perspectives of treatment and, used in combination with drugs such as proteasome inhibitors and monoclonal antibodies, represent the real “backbone” of treatment, from the first line to the following ones. “In addition to immunomodulators, proteasome inhibitors and monoclonal antibodies have also enriched the therapeutic scenario of multiple myeloma,” continues Cavo. These drugs have been usefully used first in patients with relapsed-refractory disease and subsequently in those with newly diagnosed disease, variously combined with each other or with chemotherapy drugs. The therapeutic options available in the various phases of the disease have expanded considerably, and this has translated into a significant improvement in the life expectancy of patients ”.

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The ‘triplet’ for patients who cannot have a transplant

Lenalidomide, an immunomodulating drug, in combination with a proteasome inhibitor (bortezomib) and cortisone (dexamethasone), provides patients with newly diagnosed disease and not eligible for transplant a therapeutic option that significantly extends early remission. This ‘triplet’ was approved in Europe based on the results of the SWOG S0777 study, which involved 525 patients. Median progression-free survival reached 42 months and median overall survival 89 months. From the second line, pomalidomide-based combinations represent the cornerstone. In the OPTIMISMM study, involving 559 patients and published in ‘The Lancet Oncology’, treatment with pomalidomide combined with bortezomib and dexamethasone significantly improved progression-free survival (11.2 months), with a reduced risk of progression of disease or death by 39%, and generated faster and more lasting responses in patients with relapsed or refractory multiple myeloma who received up to three prior lines of therapy.

The third line of treatment sees an important option in adding a monoclonal antibody, elotuzumab, to pomalidomide and dexamethasone. This triplet has been approved in Europe in patients with relapsed and refractory multiple myeloma who have received at least two previous lines of therapy. The approval is based on data from the ELOQUENT-3 study in 117 patients, in which the triplet doubled both the median progression-free survival (10.25 months versus 4.67 months) compared to pomalidomide and dexamethasone alone. than the overall response rate (53.3% compared to 26.3%). “The natural history of multiple myeloma has changed thanks to new drugs and, more recently, also through the increasingly massive use of immunotherapy, the doors of which have been opened by monoclonal antibodies”, continues Cavo.

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The arrival of the Car-T

Car-T’s constitute the most advanced front of immunotherapy and are showing important results in heavily pretreated patients, with approximately 80% alive at one year compared to a life expectancy that did not exceed 9 months. This therapy is based on the patient’s genetically modified lymphocytes. The procedure is complex and includes various phases: from the collection of T lymphocytes from the blood, to their engineering and expansion in the laboratory, up to their reinfusion into the patient. “Thanks to this approach – explains the hematologist – significant results are being highlighted in patients who had exhausted all therapeutic alternatives due to the refractoriness of the disease to immunomodulating agents, proteasome inhibitors and monoclonal antibodies”. Patients who, before the arrival of the Car-T, had a life expectancy ranging from 6 to 9 months. Using the best cell dosage, an overall response can be achieved in 80% of patients. “Approximately 35% achieved complete remission and had a median progression-free or other event-free survival of approximately 20 months. Not only; at one year, about 80% of patients who received Car-T cells were still alive “, concludes Cavo, adding:” About ten days ago the Food and Drug Administration approved ide-cel as the first cell-based therapy Chimeric Antigen Receptor T (CAR-T) directed against B cell maturation antigen (BCMA) for patients with relapsed / refractory multiple myeloma after four or more prior lines of therapy, including an immunomodulating agent, an inhibitor of proteasome and an anti-CD38 monoclonal antibody “.

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