This is a single-institution, single-arm, phase 2 study in which belantamab mafodotin (GSK2857916), an antibody-drug conjugate targeting B-cell maturation antigen (BCMA), will be administered to patients with multiple myeloma prior to and following high-dose melphalan and autologous stem cell transplantation (ASCT), in conjunction with standard lenalidomide maintenance. We hypothesize that administration of belantamab mafodotin as part of autologous stem cell transplant consolidation and maintenance will be safe, well tolerated, and efficacious in comparison to historical data.

Inclusion Criteria:

1. Must be able to understand the study procedures and have signed written, informed consent.

2. Must be 18 years of age or older at enrollment.

3. Must have started therapy for active multiple myeloma within 12 months of enrollment.

4. Must have an ECOG performance status of 0-2.

5. Have received no more than 2 prior lines of induction therapy (induction regimen not specified by protocol), with no prior progressive disease by International Myeloma Working Group (IMWG) criteria.

6. Must be in at least a partial response (PR) but not in a complete response (CR) or better after at least 4 cycles of induction therapy, per IMWG consensus criteria.

7. Eligible by institutional criteria to receive melphalan at a dose of 200 mg/m2.

8. Eligible to receive lenalidomide maintenance therapy post-ASCT.

9. Adequate bone marrow and organ function at enrollment.

10. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:

    1. Is not a woman of childbearing potential (WOCBP), OR
    2. Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), preferably with low user dependency, during the intervention period and for at least 4 months after the last dose of belantamab mafodotin and agrees not to donate eggs (ova, oocytes) for the purpose of reproduction during this period.

11. Male participants are eligible to participate if they agree to the following during belantamab mafodotin treatment and for 6 months after the last dose of belantamab mafodotin to allow for clearance of any altered sperm:

    1. Refrain from donating sperm PLUS either:
    2. 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 detailed in the protocol.

12. All prior treatment-related toxicities must be grade 1 or less at the time of enrollment except for alopecia.

Exclusion Criteria:

1. Must not have used an investigational drug or approved systemic anti-myeloma therapy (including systemic steroids) within 14 days or five half-lives, whichever is shorter, preceding the first dose of study drug.
2. Must not have received treatment with a monoclonal antibody within 28 days of receiving the first dose of study drug
3. Must not be simultaneously enrolled in any interventional clinical trial
4. Must not have amyloidosis or POEMS syndrome.
5. Must not be pregnant or lactating.
6. Must not have current unstable liver or biliary disease defined by the presence of ascites, encephalopathy, coagulopathy, severe hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis. Note: Stable non-cirrhotic chronic liver disease (including Gilbert's syndrome or asymptomatic gallstones) or hepatobiliary involvement of malignancy is acceptable if otherwise meets entry criteria.
7. Must not have any evidence of active mucosal or internal bleeding
8. History of an active renal condition (infection, requirement for dialysis or any other condition that could affect subject's safety). Subjects with isolated proteinuria resulting from MM are eligible, provided they fulfill other criteria.
9. Participant must not have evidence of cardiovascular risk, as defined in the protocol.
10. Must not have any serious and/or unstable pre-existing medical, psychiatric disorder, or other conditions (including lab abnormalities) that could interfere with subject's safety, obtaining informed consent or compliance to the study procedures.
11. Must not have invasive malignancies other than disease under study, unless the second malignancy has been definitively treated or has been medically stable for at least 2 years and, in the opinion of the principal investigator, will not affect the evaluation of the effects of clinical trial treatment.
12. Must not have an active infection requiring antibiotic treatment.
13. Any major surgery within the last 4 weeks prior to enrollment.
14. Must not have current corneal epithelial disease except mild changes in corneal epithelium
15. Must not have known immediate or delayed hypersensitivity reaction or idiosyncratic reactions to belantamab mafodotin or drugs chemically related to belantamab mafodotin, or any of the components of the study treatment
16. Must not have evidence for active hepatitis B infection (i.e. positive hepatitis B surface antigen or nucleic acid-based testing) at screening or within 3 months prior to first dose of belantamab mafodotin.
17. Must not have positive hepatitis C antibody test result or positive hepatitis C RNA test result at screening or within 3 months prior to first dose of study treatment.
18. Must not have evidence of active HIV infection.