Low dose mosunetuzumab treatment for indolent B-cell lymphoma

Inclusion Criteria:

* 18 years or older at time of signing informed consent
* Capable of understanding and providing written informed consent
* Histologically confirmed indolent B-cell non-Hodgkin lymphoma with no prior therapy for lymphoma. (Prior peptide-based therapeutic vaccines are allowed.) Eligible histologies include:

  * Follicular lymphoma (grade 1-2 or 3A)
  * Marginal zone lymphoma
* Ann Arbor stage II-IV disease
* No prior therapy for lymphoma
* Have low-tumor burden disease, defined by Groupe D'Etude des Lymphomes Folliculaires (GELF) criteria:

  * Nodal or extranodal tumor mass \< 7 cm
  * Involvement of less than 3 nodal sites with a diameter \> 3 cm
  * No systemic or B symptoms
  * No splenomegaly \> 16 cm by imaging
  * No local risk of vital organ compression
  * No pleural or peritoneal serous effusions
  * No leukemic phase (\> 5,0000/ uL circulating lymphocytes)
  * No significant cytopenias defined as platelets \< 100,000/uL, hemoglobin \< 10 g/dL, or absolute neutrophil count (ANC) \< 1500/ uL
* Have measurable nodal disease, including at least 1 disease site measuring at least 1.5 cm in longest dimension on CT or fludeoxyglucose F-18 (FDG)-PET, or a FDG-avid extranodal measurable site measuring at least 1.0 cm in longest dimension. Measurable disease also includes spleen size more than 13 cm in vertical length
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
* Creatinine clearance ≥ 50 mL/min calculated by Cockcroft-Gault equation
* Total bilirubin ≤ 1.5 x the upper limit of normal (ULN), except in patients with Gilbert's syndrome who may have a total bilirubin up to ≤ 3 x ULN
* Aspartate aminotransferase (AST) ≤ 3 x the ULN
* Alanine aminotransferase (ALT) ≤ 3 x the ULN
* Gamma glutamyl transferase (GGT) ≤ 3 x the ULN
* Negative serum or urine pregnancy test within 7 days of initiating mosunetuzumab for women of childbearing potential, defined as those who have not been surgically sterilized or who have not been free of menses for at least 1 year
* Fertile male and woman of childbearing potential must agree to use highly effective contraceptive methods from start of treatment to at least 3 months after the last dose of mosunetuzumab

Exclusion Criteria:

* History of severe allergic reaction to monoclonal antibody therapy
* History of a second primary malignancy that could affect compliance with the protocol or interpretation of results except with permission of the principal investigator. Malignancies treated curatively or at low-risk of progressing at the judgment of the principal investigator (PI) may be included
* Known active and uncontrolled bacterial, viral, fungal, mycobacterial, or other infection at study enrollment
* Infection with human immunodeficiency virus (unless viral load is undetectable and CD4 count ≥ 200)
* Positive test results for chronic hepatitis B infection (defined as positive hepatitis B surface antigen \[HbBsAg\] serology):

  * Patients with occult or prior hepatitis B infection (defined as positive total hepatitis B core antibody and negative HBsAg) may be included if hepatitis B virus (HBV) deoxyribonucleic acid (DNA) is undetectable at the time of screening. These patients must be willing to undergo monthly DNA testing and appropriate antiviral therapy as indicated by institutional standards
* Autoimmune disease requiring active therapy
* History of hemophagocytic lymphohistiocytosis (HLH) or macrophage activation syndrome (MAS)
* Evidence of significant concurrent disease or medical condition that could interfere with the conduct of the study, or put the patient at significant risk including, but not limited to, significant cardiovascular disease (e.g., New York Heart Association class III or IV cardiac disease, unstable arrhythmias, or unstable angina) or pulmonary disease (including obstructive pulmonary disease and history of bronchospasm)
* Ongoing systemic corticosteroid treatment, with the exception of corticosteroid use for other (non-tumor and non-immunosuppressive) indications up to a maximum of 10 mg/day of prednisone or equivalent
* Prior use of any monoclonal antibody within 4 weeks before the first mosunetuzumab administration
* Prior solid organ transplantation
* Pregnant or breast-feeding women, or intending to become pregnant during the study or within 3 months of the last dose of mosunetuzumab