The Italian Medicines Agency (Aifa) has approved the reimbursement of two Car-T cell therapies to be used in oncohematology. This is idecabtagene vicleucel (ide-cel), the first and only Car-T cell therapy for multiple myeloma, a blood cancer that originates in the bone marrow in adult patients with relapsed and refractory disease who have already received at least three previous therapies, including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody and who have demonstrated disease progression during the last treatment. As highlighted in the KarMMa study, published in the ‘New England Journal of Medicine’, the overall response rate was 73% and complete in 33% of patients for a median duration of 10.7 and 19 months respectively.
Furthermore, AIFA has approved the reimbursement of Car-T lisocabtagene maraleucel (liso-cel) in adult patients with diffuse large B-cell lymphoma (Dlbcl), primary mediastinal large B-cell lymphoma (Pmbcl) and grade 3B follicular lymphoma (Fl3B) relapsed or refractory to treatment after two or more lines of systemic therapy. In the Transcend NHL 001 study, published in ‘The Lancet’, liso-cel induced an objective response greater than 50% in 73% of patients with 53% complete remissions. The median duration of response in patients who achieved complete response was 26.1 months. Furthermore, liso-cel demonstrated an extremely favorable toxicity profile.
The new perspectives opened by Aifa’s approval in the treatment of these hematological neoplasms are explored in depth today in a press conference in Rome, promoted by Bristol Myers Squibb. Every year, in Italy, there are an estimated 5,800 new cases of multiple myeloma. “It is a typical disease of the elderly, the average age at diagnosis, in fact, is approximately 70 years – states Michele Cavo, Director of the ‘LA Seràgnoli’ Institute of Hematology, Irccs S. Orsola-Malpighi, University of Studies of Bologna and full professor of Hematology at the same University – In approximately one third of cases the pathology can begin without symptoms while, in the remaining two thirds, bone pain associated with the skeletal pathology are the most common symptoms. The disease tends to recur frequently – continues Cavo – the duration of response to therapy and life expectancy tend to reduce with each subsequent line of treatment. In particular, for patients who have undergone 3 previous lines of therapy including a proteasome inhibitor, an immunomodulator, and an anti-CD38 monoclonal antibody, the median survival has historically been 6-11 months. Ide-cel, the first and only CAR-T reimbursed in Italy for multiple myeloma, is a therapy based on autologous T cells genetically modified to express a chimeric receptor (Car) that specifically recognizes the cell maturation antigen B (Bcma), expressed on the surface of normal and malignant plasma cells”.
Ide-cel obtained reimbursement based on the results of the KarMMa study, “which enrolled 128 patients with relapsed/refractory multiple myeloma who had received at least 3 previous lines of therapy – explains the professor – Treatment with ide-cel demonstrated responses fast, deep and long-lasting, even in heavily pre-treated patients and with high-risk disease characteristics. The data updated to 24.8 months from the KarMMa study showed a median overall survival of 24.8 months, a value at least 3 times higher than the results obtained so far with standard treatments”.
Even in non-Hodgkin’s lymphomas (NHL), which affect over 14 thousand people in Italy every year, cell therapies change clinical practice. In particular, progress has been made in diffuse large B-cell lymphoma, an aggressive form characterized by the rapid growth of B lymphocytes, but also in primary mediastinal lymphoma and grade 3B follicular lymphomas. Large B-cell lymphomas represent one third of non-Hodgkin lymphoma cases and are the variant with the highest incidence. “The most frequent symptoms at diagnosis are both the enlargement of the lymph nodes in superficial or deep locations, but also visceral ones, often resulting in a serious impairment of organ function – explains Armando Santoro, director of the Cancer Center and head of the Oncology Operational Unit medical and Hematology, Irccs Humanitas Research Hospital of Rozzano, Milan – The disease is very aggressive, but today there is a good chance of cure with recovery in over 50% of cases with the new first line treatments. Unfortunately for patients who relapse or who do not achieve a response to initial therapies, treatment options have so far been limited.”
Liso-cel “is an anti-Cd19 Car-T cell therapy, a new option in relapsed or refractory large B-cell lymphoma after at least two previous therapies, which offers a potentially curative treatment to patients with a highly negative prognosis – underlines Santoro – The study Transcend NHL 001 included 270 patients treated with liso-cel. Three out of four got a response, a really important result. Furthermore, approximately 50% achieved a complete response. This is a very important result, also because this treatment is characterized by high tolerability, with a positive impact on the quality of life.” The study also included patients with primary mediastinal large B-cell lymphoma, a rare subtype of NHL that occurs increasingly in adolescents and young adults, and patients with grade 3B follicular lymphoma, an aggressive form of NHL.
“Ail has been alongside hematological patients for 55 years, supporting scientific research to improve their quality and life expectancy, accompanying them in all phases of the disease, from diagnosis to treatment time, often long and tiring – recalls Giuseppe Toro, national president of the Italian Association against Leukemia, Lymphoma and Myeloma – For this reason, the approval of reimbursement by Aifa of the first Car-T therapies in multiple myeloma and diffuse large B-cell lymphoma makes us confident. Car-T are the result of years of scientific research and the extraordinary work carried out in laboratories and in clinical practice and today constitute the spearhead of immunotherapy. Ail was born together with the first hematology departments, with the aim of financing scientific research and the development of specialized centers throughout the country. Over time, the association – continues Toro – has managed to create a solid support and assistance network, becoming a point of reference for hematology and for patients. One of Ail’s objectives is to raise awareness and inform the public, update patients and caregivers on the most recent therapies available and spread greater knowledge of the pathologies; and therefore, also on Car-T, we will continue to inform and accompany patients, so that no one ever feels alone in dealing with the disease and treatment paths”.
In this regard, Cosimo Paga, Executive Country Medical Director, Bristol Myers Squibb comments: “We are continuing to transform the therapeutic landscape in hematology, developing drugs that offer a paradigm shift. We have been pioneers in cell therapies and are engaged in what we can define as ‘personalized immunotherapy’, in which the individual patient’s cells, in particular lymphocytes, are used to counteract the development and spread of the tumor. Bristol Myers Squibb – he specifies – is the only company with two approved cell therapies, in multiple myeloma and large B-cell lymphoma, demonstrating significant investments in research and development in the sector and a strong positioning at the center of the innovation ecosystem. We have enhanced our manufacturing capacity with the construction of our fifth, state-of-the-art cell therapy manufacturing center and the first in Europe, in Leiden, the Netherlands. Furthermore, we recently entered into a global agreement with Cellares, to improve the efficiency and reduce the production time of Car-T therapies. The agreement with Cellares is the latest step in support of our global strategy to unlock the full potential of CAR-T and deliver transformative treatments to as many patients, as quickly as possible. The collaboration – concludes Paga – strengthens our current internal production capabilities, providing us with access to the first fully automated end-to-end cell therapy production platform”.
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