IMMUNOTHERAPY WITH DIFFERENTIATED T CELLS, ADULTS, AUTOLOGOUS, FROM PERIPHERAL BLOOD, SELECTED BY CD62L EXPRESSION, EXPANDED AND TRANSDUCED (GENETICALLY MODIFIED) THROUGH A LENTIVIRAL VECTOR TO EXPRESS A CHIMERIC RECEPTOR WITH ANTI-CD19 SPECIFICITY ASSOCIATED WITH CO-STIMULATORY SEQUENCES 4-1-BB AND CD3Ζ IN PATIENTS WITH B-CELL NON-HODGKIN LYMPHOMA.

Prior treatment

• Presence of active autoimmune or rheumatologic disease requiring systemic treatment with any immunosuppressor.
• Major surgery within 6 weeks prior to inclusion.
• Any concomitant anticancer treatment.
• Active CNS infiltration by lymphoma. Previous lymphoma infiltration is not exclusionary if there is evidence of absence of disease in the CNS prior to treatment.
• Patients with concomitant severe neurological or psychiatric disease.

Other illness

• General condition determined by ECOG scale: 3-4.
• Lung disease of any type that results in a DLCO < 40%.
• Active infection with HBV or HCV.
• HIV infection.
• Uncontrolled active bacterial, fungal, or viral infection.

Lab values

• Abnormal renal and hepatic function, with creatinine and/or bilirubin levels more than 2 and 4 times higher than the normal limit, respectively, except when the abnormalities are attributable to lymphoma (only in cases of hepatic alteration).
• Patients with a left ventricular ejection fraction (LVEF) less than 40%, symptomatic heart failure, or both.

Other

• Pregnant or breastfeeding patients.
• Presence of cirrhosis.

• Age > 18 years
• All patients must have measurable disease (detected by PET-CT or CT) at the time of inclusion.
• Patients with Diffuse Large B-Cell Lymphoma (DLBCL): Histological diagnosis (WHO) of LDCGB or grade 3B follicular lymphoma, and Relapsed or refractory to 2 lines of treatment (including doxorubicin and anti-CD20 monoclonal antibody) or relapse after autologous hematopoietic stem cell transplantation from peripheral blood.
• Patients with Mantle Cell Lymphoma (MCL): Histological diagnosis (WHO) of MCL, including classical and blastoid variants, and Relapsed or refractory after two lines of treatment, which must include an anti-CD20 monoclonal antibody and a BTK inhibitor, or relapse after an autologous hematopoietic stem cell transplantation in patients who previously received a BTK inhibitor.
• Patients with Follicular Lymphoma (FL): Histological diagnosis (WHO) of FL grade 1-3a, and Relapsed or refractory to two lines of treatment (including anti-CD20 monoclonal antibody) or meet the criteria for early relapse (POD24) within the first 24 months after the start of initial treatment: relapse/refractoriness after one treatment (including anti-CD20 monoclonal antibody) or relapse after autologous hematopoietic stem cell transplantation.
• General condition according to ECOG scale: 0-2.
• FEV1 > 40%; DLCO and FVC > 40% of the predicted normal values.
• Absence of significant ventricular dysfunction: left ventricular ejection fraction > 40%.
• Total bilirubin and transaminases < 4 times the upper normal limit, unless attributable to lymphoma.
• Creatinine < 2 times the upper normal limit and clearance > 40 mL/min.
• Negative serology for HIV, HBV, and HCV. For patients with positive serology for HBV or HCV, a viral load of 0 must be confirmed via quantitative PCR.
• Absence of uncontrolled active bacterial, viral, or fungal infection.
• All patients must sign an informed consent form prior to the initiation of any procedure.