ALSO patients with multiple myeloma will be able to be treated in Europe with CAR-T cell therapy. The European Commission has in fact approved the marketing – for now conditional – of idecabtagene vicleucel (ide-cel) for adult patients in whom all other treatments have failed. This is the first approval of a CAR-T therapy – which is based on the collection and modification in the laboratory of the patient’s own T lymphocytes – in this disease, and comes exactly three years from the European approvals of the first two CAR-T for the acute lymphoblastic leukemia and diffuse large B cell lymphoma
The first CAR-T for multiple myeloma
Ide-cel is also the first and only approved CAR-T therapy aimed at recognizing and binding to BCMA, a protein found on nearly all multiple myeloma cancer cells. As with other CAR-T therapies, the patient’s cells are harvested, modified to recognize and kill the target, and then reinfused with a single infusion. The “living drug” can be used in patients with at least three previous therapies (including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody) and who have demonstrated disease progression.
I’ll tell you about the CAR-T
Clinical trials of CAR-T in multiple myeloma had been ongoing for many years and Europe’s decision was awaited. Last March the FdA’s yes arrived and at the end of June the positive opinion of the Commission of the European Medicines Agency arrived. The approval is based on the KarMMa pivotal study conducted around the world, including five European countries. Bristol Myers Squibb will add a manufacturing facility in Europe in Leiden, the Netherlands, and in the meantime continue to produce vicleucel idecabtagene for EU and US patients at the cellular immunotherapy manufacturing facility in Summit, New Jersey.
Car-T against multiple myeloma: responses for three out of four patients
by Anna Lisa Bonfranceschi
Multiple myeloma
Multiple myeloma is a blood cancer in which B lymphocytes and other cells of the immune system (called plasma cells) proliferate uncontrollably and accumulate in the bone marrow. In Italy there are an estimated 6,000 cases each year. Despite the important therapeutic advances in recent years, many patients face periods of remission and relapse. “When the tumor does not respond to ongoing treatment or when it recurs, the disease becomes increasingly difficult to treat,” explains Jesus San Miguel, Medical Director of the Clinica Universidad de Navarra (Navarra, Spain) and investigator of the KarMMa clinical trial. . “In the KarMMa study, ide-cel treatment was shown to produce deep and lasting responses in a significant proportion of patients with refractory triple myeloma, including those heavily pretreated and with high-risk disease. This approval is important for European patients as it represents another potential therapeutic option for clinically meaningful results and long-term disease control. “
“Multiple myeloma patients who have tried and exhausted numerous treatment options are hoping for new treatment opportunities that can change the natural history of the disease,” adds Brian GM Durie, Chairman, International Myeloma Foundation. “The approval of idecabtagene vicleucel, an innovative anti-BCMA CAR T therapy, is an important milestone for European patients”.
Multiple myeloma, the cure becomes “precision”
by Tiziana Moriconi
Conditional authorization
The conditional marketing authorization according to the PRIME scheme (priority drugs) of the European Medicines Agency is granted in the interest of public health in the event that the benefit of immediate availability responds to an unmet critical need. It has an initial validity of one year, which can be extended or converted to the full marketing authorization, upon submission and evaluation of further confirmatory data.
The data from the KarMMa study
In the KarMMa clinical trial, involving 128 patients, 73% of global responses were obtained, of which 33% were complete. Response onset was rapid, with a median response time of one month. Furthermore, responses were durable, with a median duration of response of 10.6 months and 23 months for patients in complete response.
Multiple myeloma: with Car T, survival exceeds two years
In a pooled safety analysis of 184 patients treated with idecabtagene vicleucel in the KarMMa and CRB-401 studies, cytokine release syndrome (CRS) occurred in 81% of patients, 5.4% of patients had a severe degree (higher than). One fatal case of cytokine release syndrome (Grade 5) has been reported. The median time to onset of CRS was one day (range: 1-17 days) and the median duration of CRS was five days (range: 1-63 days). Neurotoxicity (NT) occurred in 18% of patients, with Grade 3 events in 3.1% of patients, and no Grade 4 or 5 events. Median time to onset of NT was two days (range : 1-10 days) and the median duration of three days (range: 1-26 days).
CAR-T cells: so in the future we can turn them off and on
by Anna Lisa Bonfranceschi
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