New combination therapy for the most common form of non-Hodgkin’s lymphoma and its aggressive forms

Large B-cell lymphoma is an aggressive disease and the most common type of non-Hodgkin’s lymphoma. Unfortunately, in its aggressive forms, relapse occurs early. Despite advances in research, it is unfortunately not always possible to keep the disease under control, and up to four in ten patients may develop a refractory form of the disease or, in any case, no longer respond to first-line treatments. As if that were not enough, in addition to the risk of relapse, the time at which it recurs is also a key factor in determining future treatment. “A relapse within 12 months generally points towards CAR-T therapy, whilst a relapse after 12 months may point towards an autologous stem cell transplant,” comments Carmelo Carlo-Stella, Full Professor of Haematology, Director of the Postgraduate School of Haematology at Humanitas University in Milan and Director of the Haematology Division at the IRCCS Humanitas Research Hospital in Milan. “However, both options are reserved for eligible patients or those for whom these treatments are deemed appropriate”. So what then? We need to address an unmet clinical need for those who cannot access these treatment options.

A new treatment option is now available for these patients, provided, of course, that CAR-T therapy or autologous bone-marrow transplantation are not viable options. This involves combining the bispecific antibody (which, in practice, can bind to two different sites, thereby triggering a response that leads to the death of the cancer cell) glofitamab with standard chemotherapy, namely gemcitabine and oxaliplatin (GemOx). This approach, which essentially activates the immune system against the tumour in addition to chemotherapy, is available and reimbursed in Italia for the treatment of patients with diffuse large B-cell lymphoma who have relapsed or whose disease is refractory following first-line treatment. “Having new treatment options available for this patient group in second-line therapy means intervening at a crucial stage of the patient’s clinical journey, offering a valuable opportunity to control the disease,” the expert explains. Clinical research, in particular, shows that the combination leads to a significant improvement in overall survival and progression-free survival compared with the standard of care. “In particular, we believe that its value in treating refractory disease, even in the frail and older population, combined with a manageable safety profile, could make this combination a therapeutic option of great interest in clinical practice – emphasises Paolo Corradini, Full Professor of Haematology at the University of Milan and Director of the Haematology Division at the IRCCS National Cancer Institute Foundation in Milan – this additional option. “In theory, it could also enable us to treat more people effectively and for longer periods, perhaps overcoming certain inflexibilities, thereby improving the use of resources.”

It must be said that, as well as proving effective, this therapy also has a number of significant practical advantages in terms of the organisational model for its administration. Firstly, it is ‘off-the-shelf’, meaning it is immediately available – an important factor for patients whose condition may worsen if not treated promptly. But that is not all. The duration of treatment is established from the outset: a fixed number of cycles is planned, which gives the patient a definite end date and a treatment-free period, thereby improving their quality of life. “Receiving a diagnosis of lymphoma or facing a relapse means seeing one’s own life and that of one’s loved ones suddenly put on hold, caught between fear of the future and the need for answers that are as swift and effective as possible,” notes Davide Petruzzelli, president of La Lampada di Aladino ETS. “As well as offering hope, the availability of ready-to-use, fixed-duration therapies means providing new opportunities for those with limited options, whilst also easing the emotional and organisational burden placed on families.”