Marginal Zone Lymphoma (MZL) Clinical Trials

• Have a biopsy proven diagnosis of MZL, extranodal (EMZL) or nodal (NMZL) Or have a diagnosis of splenic MZL (SMZL) based on mandatory 13 flow cytometry markers: surface immunoglobulins (SmIg), CD5, CD23, FMC7, CD22 or CD79b, CD200, CD180, CD20, CD43, CD11c, CD10,CD103 and CD123 and validated by a centralized review.

• In case of large dissemination, disseminated MZL (as evaluated by investigator; please contact the Sponsor to discuss any doubt) will be included as DMZL and included in NMZL subtype. Participants with high tumor burden criteria are eligible.

• Participants with borderline or related entities, such as splenic diffuse red pulp lymphoma (SDRPL), typical hairy cell leukemia (HCL), and HCL variant (HCLv), are not eligible.

• Have been treated with at least one prior systemic treatment and not more than three prior lines. Previous line must include at least one systemic line with a drug targeting CD20 (monoclonal antibody at least 2 cycles; participants treated with monoclonal antibody monotherapy should have received at least 4 weekly injections) with or without chemotherapy (R-CHOP, R-Bendamustine, R-CVP, R-Chlorambucil at least 2 cycles) or targeted treatment such as BTK inhibitors (at least 1 month). Participants previously treated by lenalidomide are eligible if the last administration of lenalidomide is superior to 12 months before C1D1. When randomized in comparator arm, those participants should require R-chemo. Prior local therapy (including surgery, radiotherapy antibiotics for H. pylori-positive gastric lymphoma, and antiviral for hepatitis C virus) is not considered as one line of treatment

• Signed Informed Consent Form

• Age ≥ 18 years at the time of signing the informed consent form

• Ability to comply with the study protocol and procedures and required hospitalizations, in the investigator's judgement

• Eastern Cooperative Oncology Group (ECOG) performance score (PS) of ≤ 2

• Have a symptomatic disease requiring a systemic treatment

• Not eligible for a local treatment including radiotherapy or surgery

• Stage I disease of EMZL, SMZL or NMZL may be eligible only if not candidate to local therapy (surgery or radiotherapy).

⁃ Measurable disease in at least two perpendicular dimensions on an imaging scan is defined as: lymph node or nodal mass bi-dimensional measurement with ≥ 15 mm in longest transverse diameter or the short diameter must measure ≥ 10 mm regardless of the longest transverse diameter.

⁃ Spleen is considered as a measurable disease if vertical axis is higher than 130 mm.

⁃ Adequate hematopoietic function at screening as follows unless cytopenia is clearly due to marrow involvement of MZL or hypersplenism or autoimmune thrombocytopenia:

∙ 1. Platelet count ≥ 75 G/L; in cases of thrombocytopenia clearly due to marrow involvement of MZL or hypersplenism or auto-immune thrombocytopenia, platelet count should be ≥ 30 G/L. Washout platelet transfusion is 7 days between transfusion and D1 of starting treatment 11.2. Absolute Neutrophil Count (ANC) ≥ 1 G/L unless neutropenia is clearly due to marrow involvement of MZL or hypersplenism. G-CSF is not allowed within 7 days before starting treatment 11.3. Total hemoglobin ≥ 8 g/dL unless anemia is clearly due to marrow involvement of MZL or hypersplenism or autoimmune hemolytic anemia. Washout erythrocyte transfusion is 7 days between transfusion and D1 of starting treatment

⁃ Serum total bilirubin ≤ 1.5 x the upper limit of normal (ULN) (or ≤3 x ULN for participants with Gilbert syndrome),

⁃ AST or ALT ≤ 2.5 x ULN, unless directly attributable to the participant's MZL

⁃ Measured or estimated creatinine clearance ≥ 40 mL/min by institutional standard method

⁃ Participants who are hepatitis B surface antigen (HBsAg) negative and hepatitis B core antibody (HBcAb) positive, must be negative for hepatitis B virus (HBV) polymerase chain reaction (PCR) to be eligible for study participation. Participants who are hepatitis B surface antigen (HBsAg) negative, hepatitis B surface antibody (anti-HBsAb) positive and hepatitis B core antibody (HBcAb) negative are eligible,

⁃ Contraception:

∙ 1. For women of childbearing potential (WOCBP) (refer to section 14.6.1):

‣ must have a negative result for pregnancy test (highly sensitive serum) within 7 days before randomization and within 7 days before initiation of study treatment.

‣ must agree to abstain from becoming pregnant or breastfeeding, and agree to use highly effective contraceptive methods during study participation, and for at least 28 days after the final dose of lenalidomide (if applicable), 3 months after the final dose of mosunetuzumab and tocilizumab (if applicable), 12 months after the final dose of CHOP (if applicable), 6 months after the final dose of bendamustine (if applicable) and 12 months after the final dose of rituximab (if applicable).

∙ 2. For men: with a female partner of childbearing potential or pregnant female partner, men must remain abstinent or use a condom during the treatment period (including periods of treatment interruption), and for at least 28 days after the final dose of lenalidomide (if applicable), 2 months after the final dose of tocilizumab (if applicable), 6 months after the final dose of CHOP (if applicable), 3 months after the final dose of bendamustine and 12 months after the final dose of rituximab (if applicable). ). Men must also agree to refrain from donating sperm from the first day of treatment until at least 7 days after the final dose of lenalidomide (if applicable), 2 months after the final dose of tocilizumab (if applicable), 6 months after the final dose of CHOP (if applicable), 3 months after the final dose of bendamustine (if applicable), and 12 months after the final dose of rituximab (if applicable)

⁃ Participants covered by any social security system (France).

⁃ Participants who understand and speak one of the country official languages.

⁃ LVEF within normal range (i.e. \> 50% as evaluated by Transthoracic Echocardiography or \> 45% as evaluated by isotopic method (MUGA scan)).