Mosunetuzumab With or Without Polatuzumab Vedotin and Obinutuzumab for the Treatment of Untreated Indolent B-Cell Non-Hodgkin Lymphoma

Inclusion Criteria

• Diagnosis of indolent B-cell non-Hodgkin lymphoma with no prior systemic therapy.
• Eligible histologies based on 2016 World Health Organization (WHO) classification include:
• Follicular lymphoma (grade 1-2 or 3a)
• Marginal zone lymphoma. Patients with mucosa-associated lymphoid tissue (MALT) subtype of marginal zone lymphoma (MZL) may have relapsed or refractory disease after a course of antibiotic therapy
• Meet criteria for initiation of therapy that include one of the following:
• Symptomatic disease (including but not limited to pain/discomfort, b-symptoms)
• Threatened end-organ function
• Progressive cytopenias (leukopenia [WBC = 18 years of age on day of signing informed consent
• Have measurable fludeoxyglucose F-18 (FDG)-avid nodal disease, including at least 1 disease site measuring at least 1.5 cm in longest dimension on computed tomography (CT) or FDG-positron emission tomography (PET), or FDG-avid extra nodal measurable site measuring at least 1.0 cm in longest dimension
• Have a performance status of 0-2 on the ECOG Performance Scale (PS)
• Absolute neutrophil count (ANC) >= 1, 000/uL except in cases of marrow infiltration by lymphoma
• Platelets >= 75, 000/mcL except in cases of marrow infiltration by lymphoma or hypersplenism
• Hemoglobin >= 8 g/dL except in cases of marrow infiltration by lymphoma without red blood cell (RBC) transfusion within 14 days of first treatment
• Measured or calculated creatinine clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]) >= 40 mL/min; Note: Creatinine clearance should be calculated per institutional standard
• Serum total bilirubin = 1.5 ULN
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT)] (serum glutamate pyruvate transaminase [SGPT]) = 5000/uL
• History of autoimmune disease, including but not limited to myocarditis, pneumonitis, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjogren's syndrome, Guillain Barre syndrome, multiple sclerosis, vasculitis, or glomerulonephritis
• Patients with a remote history of, or well-controlled autoimmune disease, may be eligible to enroll after discussion with and confirmation by the principal investigator. Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study
• Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone may be eligible for this study
• Patients with a history of disease-related immune thrombocytopenic purpura or autoimmune hemolytic anemia may be eligible for this study
• Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met:
• Rash must cover 1 peripheral neuropathy by clinical examination or demyelinating form of Charcot-Marie-Tooth disease
• Prior use of any monoclonal antibody within 3 months of the start of cycle 1; any investigational therapy within 28 days prior to the start of cycle 1; vaccination with live vaccines within 28 days prior the start of cycle 1
• Prior corticosteroid use for conditions related or unrelated to lymphoma are allowed provided that at least 14 days have lapsed since last dose and initiation of study therapy, except for patients who require corticosteroid pre-medication for IV contrast administration
• History of other malignancy that could affect compliance with the protocol or interpretation of results except with permission of the principal investigator. The following are eligible without a specific waiver:
• Patients with a history of curatively treated basal or squamous cell