Diffuse large B-cell lymphoma, a new treatment available for patients already undergoing two or more lines of therapy

Diffuse large B-cell lymphoma, the most common form of non-Hodgkin lymphoma, represents approximately 30% of all aggressive lymphomas, which have a more rapid clinical course and require timely treatment. It is a blood cancer characterized by rapid growth of B lymphocytes, a type of white blood cell (immune system cell), which is diagnosed around 13,200 Italians every year. Although a considerable proportion of patients respond positively to initial treatment, nearly four in ten show no response or experience a relapse. Just for me relapsed or refractory patients, after two or more lines of systemic therapythe Italian Medicines Agency (Aifa) has recently granted reimbursement to a new medicine, glofitamab.

Bispecific antibodies

«Patients with this hematological neoplasm, heavily pre-treated or refractory, unfortunately had few therapeutic alternatives – he clarifies Paolo Corradini, full professor of Hematology at the University of Milan -. 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. The data confirm the important role of CD20xCD3 bispecific antibodies in the treatment of non-Hodgkin B lymphomas, both aggressive and indolent, showing how a defined duration therapy can determine complete and 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 diffuse large B-cell lymphoma and follicular lymphoma.” Bispecific antibodies are called this because they are composed of two parts: one recognizes the target on the surface of the tumor cell and the other binds to a healthy T cell of our immune system bringing it close to the tumor cellthen the T cell activates and destroys it.

A new type of immunotherapy

Glofitamab is a new type of immunotherapy: its mechanism of action makes it particularly effective and capable of inducing complete, fast and lasting responses in patients with lymphomas heavily pretreated or refractory to previous therapies, including CAR-T. Furthermore, his administration for a fixed period of time (12 cycles of 21 days, equal to about 8 months) lets patients know when treatment will end. «Aifa's approval of glofitamab represents a significant milestone in the fight against diffuse large B-cell lymphoma, which presents considerable therapeutic challenges, with a significant number of patients who do not benefit from current standards of care – he says Carmelo Carlo-Stella, full professor of Hematology at Humanitas University and head of the Lymphoid Neoplasms section at the IRCCS Humanitas Clinical Institute in Milan -. Data from clinical trials demonstrate that glofitamab is capable of maintain remissions in many heavily pretreated patients, thus offering new hope. Thanks to its targeted design, which involves CD20 on malignant B cells and CD3 on T cells, the molecule activates a specific immune response against tumor cells.”

Patient associations

The approval by Aifa is based on results of the registration study (phase I/II NP30179) which, with an updated median follow-up of 32 months, demonstrated how glofitamab is able to maintain complete responses over time, administered for a maximum of 12 cycles (approximately eight months), in patients with relapsed or refractory diffuse large B-cell lymphoma who had received at least two prior lines of therapy. Indeed, after such a long-term median follow-up, 55% of patients with a complete response (CR, complete response) was 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. Glofitamab also results well tolerated. The most common adverse event was cytokine release syndrome, but limited to the first cycle and manageable. Discontinuations due to adverse events were rare and occurred in only 2.8% of patients.

Save precious time

«In hematology oncology, research is accustoming us to continuous innovation that is slowly changing the history of various diseases, even in advanced stages or in situations with few therapeutic prospects – he comments Davide Petruzzelli, president of the Aladdin's Lamp association -. The approval of glofitamab offers patients an important opportunity and introduces elements that can significantly impact the quality of life, such as the fixed duration of therapy which allows them to gain precious time to dedicate to themselves again, but also its distribution widespread throughout the territory which facilitates access”. «As a patient association committed for over 50 years to providing support and information to those fighting against onco-haematological pathologies, the approval of this innovative therapy makes us happy and confident because it allows us to facilitate treatment and gives patients the opportunity to gain precious time by avoiding prolonged hospitalization” he concludes Giuseppe Gioffrè, AIL lymphoma patient group representative.