⁃ Patients must be diagnosed with high-risk smoldering multiple myeloma (SMM) as confirmed by the following (all three must be present):

• Bone marrow plasmacytosis with ≥ 10% plasma cells in bone marrow biopsy

• Immunoparesis (reduction in at least one uninvolved immunoglobulin in blood)

• ≥ 95% aberrant plasma cells of all plasma cells by flow cytometry of the bone marrow aspirate

‣ Creatinine clearance (CrCl) ≥ 30 ml/min. CrCl will be calculated using the Modification of Diet in Renal Disease (MDRD) equation.

⁃ Age ≥ 18 years.

⁃ Eastern Cooperative Oncology Group (ECOG) performance status 0-2

⁃ Absolute neutrophil count (ANC) ≥ 1.0 x 109 /L, hemoglobin more or equal than 2 grams below the institutional level of normal and platelet count ≥ 90 x 109/L. Platelet and blood transfusions are allowed on protocol. Growth factors, including granulocyte colony stimulating factors and erythropoietin are allowed.

⁃ Adequate hepatic function, with bilirubin ≤ 1.5 x the ULN, and AST and ALT ≤ 2.5 x ULN.

⁃ Females of childbearing potential are eligible to participate if they agree to avoid pregnancy by using an adequate method of contraception that is highly effective with a failure rate of \<1% per year (2 barrier method or 1 barrier method with a spermicide or intrauterine device during and for 4 months after the last dose of belantamab mafodotin). Adequate methods of contraception are provided as examples. Other acceptable and effective methods of birth control are also permitted (eg, abstinence). Women of child bearing potential must have a negative serum pregnancy test result within 72 hours prior to the first administration of belantamab mafodotin and at the end of treatment visit. A negative urine pregnancy test is required prior to each subsequent belantamab mafodotin dose administration

⁃ Females of childbearing potential are eligible to participate if they agree to notdonate eggs (ova, oocytes) for the purpose of reproduction during the study and for 4 months after the last dose of belantamab mafodotin.

⁃ Male participants are eligible to participate if they agree to the following from the time of first dose of belantamab mafodotin until 6 months after the last dose of study treatment to allow for clearance of any altered sperm:

• be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent,

∙ OR must agree to use contraception/barrier as follows:

∙ agree to use a male condom, even if they have undergone a successful vasectomy

∙ and female partner of childbearing potential to use an additional highly effective contraceptive method with a failure rate of \<1% per year when having sexual intercourse.

⁃ Men must agree to not donate sperm while on the study and for at least 6 months after the last dose of belantamab mafodotin.

⁃ Subjects must be able to give informed consent.

⁃ Subjects must be either newly diagnosed smoldering myeloma or not have received prior or concurrent treatment for smoldering multiple myeloma with chemotherapy agents approved for the treatment of smoldering multiple myeloma. Patients who have been treated previously on a clinical trial or with non-approved agents for their smoldering myeloma can be included.