The therapy that focuses on the immune system to tackle cancer scores another point in its favor. The goal is a molecule that has several unique characteristics: it is a monoclonal antibody constructed to maximize action against tumor cells while minimizing side effects. Furthermore, its administration is for a fixed period of time – approximately 8 months – and therefore allows patients to know when the treatment will end. It is called glofitamab and has been authorized by the Italian Medicines Agency for the treatment of adult patients with diffuse large B-cell lymphoma (DLBCL) in cases where the disease does not respond to drugs or has returned after two or more lines of systemic therapy .
Lymphomas, European green light for the double specific attack by Dario Rubino 19 July 2023
A unique drug
Glofitamab is a bispecific monoclonal antibody: a molecule designed to be able to connect T lymphocytes, the cells of the immune system, on one side, and lymphoma cells on the other, activating the former against the latter. Not only. “To date, glofitamab is the only drug in this class with a 2:1 configuration that allows it to maximize binding to diseased cells through two bonds with the CD20 receptor present on them and not activate T lymphocytes too much, and therefore it does not cause excessive immune activity which could lead to toxicity, since it only has one link to them through the CD3 protein”, explains Carmelo Carlo-Stella, Full Professor of Hematology, Humanitas University; Director of the School of Specialization in Hematology, Humanitas University; Head of the Lymphoid Neoplasms Section, IRCCS Humanitas Research Hospital. A mechanism of action that makes it particularly effective and capable of inducing complete, fast and long-lasting responses in patients with lymphomas that do not respond to therapies or have already been treated, even with CAR-Ts.
The other characteristics that make glofitamab a simple solution to manage for both the patient and the clinician are the fixed duration of treatment – 8 months – and the fact that it is a chemotherapy-free and ready-to-use monotherapy, unlike other options therapeutics which must be prepared and manipulated for a rather long period of time before being administered, which may become “too” long for patients at high risk of disease progression. “This innovation introduces elements that can significantly impact the quality of life, such as the fixed duration of the therapy which allows you to gain precious time to dedicate to yourself again, but also its widespread distribution across the territory which facilitates access. Furthermore, the compassionate use program which helps to bring forward the start of treatment is also providing considerable support,” said Davide Petruzzelli, president of Lampada di Aladino.
DLBCL is the most common form of non-Hodgkin lymphoma, and although patients usually respond to the first treatment they receive, in 40% of cases, within the first 12 months, the drugs do not work or the disease returns. In these patients the objective would be to continue with the stem cell transplant but in 60-65% of cases the procedure cannot be performed or does not work. “Heavily pretreated or refractory DLBCL patients unfortunately had few therapeutic options. In recent years the therapeutic panorama has been enriched with new innovative and effective therapies and the approval of glofitamab represents one of these innovations”, explains Paolo Corradini, Full Professor of Hematology at the University of Milan. “The glofitamab data confirm the important role of CD20xCD3 bispecific antibodies in the treatment of both aggressive and indolent non-Hodgkin B lymphomas, showing how a defined duration therapy can determine complete and long-lasting responses even after the end of treatment. From this perspective, the rationale of ongoing clinical studies is also confirmed, in which bispecific antibodies are tested in combination strategies in the early treatment lines of DLBCL and follicular lymphoma”.
Scientific studies have shown that glofitamab is able to maintain complete responses that lasted over time: 55% of patients who achieved complete response were still in remission at 24 months. The majority of these patients remained progression-free and were still alive 18 months after completing fixed-duration treatment with glofitamab. Efficacy is maintained even in the most compromised patients who had previously received CAR-Ts.
“As a patient association committed for over 50 years to providing support and information to those fighting against onco-haematological diseases, the approval of this innovative therapy makes us happy and confident. Glofitamab, in fact, makes it possible to facilitate the processes linked to treatment and gives patients the opportunity to gain precious time by avoiding prolonged hospitalization”, concludes Giuseppe Gioffrè, AIL lymphoma patient group representative.