Mosunetuzumab for Early Relapse of Follicular Lymphoma in the Nordic Countries

Inclusion Criteria:

1. Written informed consent according to ICH-GCP guidelines.
2. Age ≥ 18 years.
3. Follicular lymphoma grade 1-3a with a current relapse or progression within 24 monthsof starting 1st line treatment or refractory to 1st line treatment (POD24), morespecifically:
4. Documented current relapse or progression of FL within 24 months of startingfirst line treatment containing a monospecific anti-CD20 antibody (such asrituximab or obinutuzumab with or without chemotherapy, small molecularinhibitors or immunomodulating agents such as lenalidomide).
5. Current lack of response/refractoriness to first line treatment, i.e., noobjective response or documented progression within 6 months following at leastfour cycles of monotherapy with a monospecific anti-CD20 antibody (such asrituximab 375mg/m2 iv or 1400 mg SC or equal) or following at least three cyclesof a monospecific anti CD20 antibody combined with chemotherapy, small molecularinhibitors or immunomodulating agents such as lenalidomide.
6. Received one prior treatment line of systemic therapy.
7. Patients may have had a period of watch and wait before the initiation of firstline treatment.
8. Patients may have received localized radiotherapy previously.
9. At least one two-dimensionally measurable lesion with a longest diameter >15mm.
10. WHO performance status 0-2. Patients with reduced WHO performance status (> 2) can beconsidered if reduction in performance is caused by the lymphoma as determined by theinvestigator.

Exclusion Criteria:

1. Received 2 or more previous treatment lines.
2. Grade 3b FL.
3. CD20-negative lymphoma.
4. CNS involvement (current or previous).
5. Impaired bone marrow function (neutrophils < 1.0 x 109/L or platelets < 50 x 109/L)unless due to lymphoma involvement.
6. Severe cardiac disease: impaired cardiac function (NYHA class III or IV), myocardialinfarction within the last 6 months, unstable arrythmias and/or unstable anginapectoris.
7. Impaired liver function not caused by lymphoma, defined as serum total bilirubin ≥ 1.5x ULN (unless elevated due to Gilbert's syndrome) or serum ALT and AST > 3 x ULN.
8. Impaired renal function not caused by lymphoma, defined as calculated creatinineclearance ≤ 40 ml/minute.
9. Other major organ dysfunction not caused by lymphoma.
10. Known history of drug induced liver injury, chronic active hepatitis C (HCV), chronicactive hepatitis B (HBV), alcoholic liver disease, primary biliary cirrhosis, on-goingextra-hepatic obstruction caused by cholelithiasis, cirrhosis of the liver or portalhypertension.
11. Active severe infection.
12. Hepatitis B (HBV) or hepatitis C (HCV) infection: Subjects with a previous hepatitis Binfection will be eligible if they are negative for HBV-DNA; these subjects must begiven prophylactic antiviral therapy. Subjects with a previous HCV infection will beeligible if they are negative for HCV-RNA.
13. Known or suspected chronic active Epstein-Barr virus (EBV) infection.
14. Received systemic immunosuppressive medications (including but not limited tocyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosisfactor agents) within two weeks prior to the first dose of mosunetuzumab.
15. Administration of live vaccines within four weeks of the first dose of mosunetuzumabor anticipation that live vaccine will be required during the study.
16. History of severe allergic or anaphylactic reactions to chimeric, human, or humanizedantibodies, or fusion proteins.
17. Known or suspected hemophagocytic syndrome.
18. Prior allogeneic hematopoietic stem cell transplant.
19. Other current severe medical problems or expected survival of less than approximatelyfive years for non-lymphoma reasons.
20. Current or previous other malignancy within three years of study entry, except curedbasal or squamous cell skin cancer, superficial bladder cancer, prostateintraepithelial neoplasm, carcinoma in situ of the cervix, or other non-invasive orindolent malignancy without sponsor approval.
21. Psychiatric disorder or dementia which make the patient unable to give an informedconsent and/or adhere to the schedule.
22. Pregnancy or breast-feeding.
23. HIV positivity: Subjects that are on HIV-treatment with undetectable HIV-RNA andCD4-counts above 200 will be eligible.
24. Women of reproductive potential not agreeing to use an acceptable method of birthcontrol during treatment and for three months after completion of treatment.