Bispecific antibodies have demonstrated high efficacy in the treatment of Refractory/relapsed b-cell non-Hodgkin lymphomas. However, a non-negligible percentage of patients do not respond to therapy and/or develop significant treatment toxicity.

This exploratory study aims to obtain a first identification of clinical and biological characteristics related to response and toxicity to bispecific antibodies.

Having this information, currently not available in the scientific literature and to be validated in further studies, therapies with BsAbs can be addressed only to patients for whom they have proven useful, improving the results of the therapy pharmacological (more responses and less toxicity) and consequently the sustainability and efficiency of the healthcare system.

Inclusion Criteria:

• Age≥18 years
• Patients with histologically documented non-Hodgkin B lymphoma, with relapsed/refractory disease and candidates for BsAbs therapy (glofitamab, epcoritamab, mosunetuzumab) according to clinical indication and AIFA reimbursement criteria
• obtaining signed and dated informed consent before the start of any screening or study-specific procedure

Exclusion Criteria:

• Evidence of concomitant and uncontrolled diseases that could affect protocol compliance or interpretation of results.
• Concomitant secondary neoplasm.

This is a single-center, observational pharmacological, non-profit study with a tissue component and collection of biological samples, which involves a prospective enrollment of patients treated with BsAbs who will be followed for a period of at least 18 months. All patients will be treated according to clinical practice and will follow the clinical care pathway required by the standard operating procedures of the IRCCS AOUBO Hospital Authority.

The search for biomarkers predictive of response and toxicity, as well as the description of potential resistance mechanisms to BsAbs treatment, will be conducted by a multidisciplinary team involving several Operational Units (UOs) of the IRCCS AOUBO.

In particular, the units involved in the specific study analyses will be the Nuclear Medicine Operational Unit, Hemolymphopathology, Gastroenterology and Digestive Endoscopy, Internal Medicine and Digestive Pathophysiology and the Biology and Molecular Medicine Platform, Intestinal Microbiomics.