Mosunetuzumab With Lenalidomide Augmentation as First-line Therapy for Follicular and Marginal Zone Lymphoma

Inclusion Criteria: 1. Ability to understand and the willingness to sign a written informed consent document and to comply with the study protocol procedures. 2. Age ≥18 years at the time of signing informed consent. Because no dosing or adverse event data are currently available on the use of mosunetuzumab in patients \<18 years of age, they are excluded from this study. 3. Histologically confirmed diagnosis of: * follicular lymphoma (grade 1, 2, 3a, or not otherwise specified) or * marginal zone lymphoma (nodal, extranodal, or splenic), according to 2016 WHO classification and confirmed to express the CD20 antigen by immunohistochemistry or flow cytometry. Patients in whom definitive pathologic subtype of FL/MZL is undetermined due to limited biopsy material can be enrolled if in the investigator's opinion integrated clinicopathologic data are consistent with the eligible diagnosis. 4. Agreement to provide, if available, lymphoma tissue for correlative analyses. 5. At least one bi-dimensionally measurable nodal lesion, defined as \>1.5 cm in its longest dimension, or one bi-dimensionally measurable extranodal lesion, defined as \>1.0 cm in its longest diameter; with the exception of splenic MZL, which must be evaluable using the International SMZL Group criteria. 6. No prior systemic therapy for B-cell lymphoma, except for palliative corticosteroids; prior local therapy (surgery, radiation therapy, or antibiotics) is allowed. 7. Indication to start systemic therapy for lymphoma: * Patients with FL must meet one of the GELF criteria: * any mass ≥7 cm (except spleen); * at least 3 nodes \>3 cm in diameter; * symptomatic spleen enlargement; * local symptoms or compromise of normal organ function due to tumor mass; * presence of ascites or pleural effusion; * presence of B symptoms (fever, night sweats, or unintentional weight loss of \>10% over ≤6 months); * serum lactate dehydrogenase or beta-2-microglobulin above upper limit of normal; * cytopenias due to underlying lymphoma (i.e., absolute neutrophil count \<1.0 × 109/L, hemoglobin \<10 g/dL, and/or platelet count \<100 × 109/L). * Patients with MZL must have an indication to start therapy as assessed by the investigator. 8. Performance status ECOG 0, 1, or 2. 9. Adequate hematologic function (unless due to underlying lymphoma as established by bone marrow involvement or splenomegaly): * hemoglobin ≥9 g/dL, * absolute neutrophil count ≥1.0 x 109/L, * platelet count ≥75 x 109/L. 10. Glomerular filtration rate (GFR) ≥40 mL/min/1.73m2 using the Mayo Quadratic Formula. 11. The effects of mosunetuzumab on the developing human fetus are unknown. For this reason and because lenalidomide used in this trial is known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) and refrain from donating eggs or sperm throughout the treatment and for 3 months after the last dose of trial therapy. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. 12. Agreement to enroll in and comply with all local requirements of the REVLIMID® (lenalidomide) Risk Evaluation and Mitigation Strategy (REMS®) program for the purpose of lenalidomide acquisition. Exclusion Criteria: 1. Grade 3b follicular lymphoma or transformed lymphoma. 2. Prior treatment with any anti-CD20 antibody or lenalidomide for lymphoma. 3. Prior stem cell transplantation (autologous or allogeneic) or prior solid organ transplantation. 4. History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies or known sensitivity or allergy to murine products. 5. Known NYHA class 3/4 congestive heart failure, LVEF \<40%, myocardial infarction within 6 months prior to enrollment, unstable angina, or unstable arrhythmia. 6. Chronic obstructive pulmonary disease (COPD) requiring oral corticosteroids or chronic oxygen. 7. History of autoimmune disease, including, but not limited to myasthenia gravis, myositis, autoimmune hepatitis, idiopathic pulmonary fibrosis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid syndrome, granulomatosis with polyangiitis, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis, with the exception of: hypothyroidism (on stable dose of thyroid replacement therapy), asthma managed with inhaled medications only; type 1 diabetes mellitus on stable insulin regimen, Sjögren syndrome, immune thrombocytopenia or autoimmune hemolytic anemia that does not require systemic therapy; dermatologic condition (including eczema, psoriasis, lichen simplex chronicus, or vitiligo) with skin manifestations with rash covering \<10% of body surface area and not requiring treatment other than low-potency topical corticosteroids for \>12 months prior to registration. 8. Use of any systemic immunosuppressive medications (including, but not limited to, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents) with the exception of corticosteroid treatment using \<10 mg/day prednisone or equivalent within 2 weeks prior to first treatment; a brief course of palliative corticosteroids at higher doses (prednisone up to 100 mg daily, for up to 7 days) is allowed, but must be completed at least 7 days before the first dose of mosunetuzumab. 9. Any of the following conditions: * active bacterial infection requiring antibiotics * known or suspected chronic active Epstein Barr virus (CAEBV) infection * history of hemophagocytic lymphohistiocytosis (HLH) * confirmed progressive multifocal leukoencephalopathy (PML) * known active EBV or CMV viremia * positive test for hepatitis B surface antigen (HBSAg). Patients with a positive total/IgG hepatitis B core antibody (HBcAb)