Inclusion Criteria:
1. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form and in the REBEL study protocol.
2. Male or female, 18 years or older (at the time consent is obtained).
3. Have a confirmed diagnosis of MM as defined by the IMWG criteria.
4. Eastern Cooperative Oncology Group performance status of 0-2.
5. Have been previously treated with at least 1 prior line of MM therapy, including a lenalidomide-containing regimen (lenalidomide must have been administered for at least 2 consecutive cycles), and must have documented disease progression during or after their most recent therapy.
6. Must have at least ONE aspect of measurable disease, defined as one the following:
1. Urine M-protein excretion ≥200 mg/24 h, or
2. Serum M-protein concentration ≥0.5 g/dL (≥5.0 g/L), or
3. Serum free light chain (FLC) assay: involved FLC level ≥10 mg/dL (≥100 mg/L) and an abnormal serum free light chain ratio (\<0.26 or \>1.65) only if the patient has no measurable urine or serum M spike.
7. Have undergone autologous stem cell transplant (autoSCT) or are considered transplant ineligible. Participants with a history of autoSCT are eligible for study participation provided the following eligibility criteria are met:
1. AutoSCT was \>100 days prior to the first dose of study medication
2. No active bacterial, viral, or fungal infection(s) present
8. All prior treatment-related toxicities (defined by National Cancer Institute Common Toxicity Criteria for Adverse Events v5.0) must be Grade ≤1 at the time of enrolment, except for alopecia and Grade ≤ 2 peripheral neuropathy.
9. Compliance with contraceptive precautions in accordance with the protocol.
10. Organ System Function - adequate organ system functions as defined by the laboratory assessments
* Hematologic:
* Absolute neutrophil count - ≥1.5× 10 9/L (Without growth factor support for the past 14 days, excluding erythropoietin)
* Hemoglobin - ≥8.0 g/dL
* Platelets - ≥75 × 10 9/L
* Hepatic:
* Total bilirubin - ≤1.5 × ULN; (isolated bilirubin \>1.5 × ULN is acceptable if bilirubin is fractionated and direct bilirubin is \<35%)
* Alanine aminotransferase (ALT) - ≤2.5 × ULN
* Renal o eGFR ≥30 mL/min/1.73 m2 (as calculated by MDRD formula)
Exclusion Criteria:
1. Active plasma cell leukemia, amyloidosis, POEMS syndrome, allogeneic SCT or currently active GvHD.
2. Anti-MM therapy or use of an investigational drug within 14 days or five half-lives (whichever is shorter) preceding the first dose of study drug; Prior treatment with a monoclonal antibody drug within 30 days of receiving the first dose of study drugs.
3. Plasmapheresis within 7 days prior to the first dose of study drug.
4. Prior treatment with pomalidomide and belantamab mafodotin in any treatment line.
5. Evidence of cardiovascular risk including: current clinically significant (CS) untreated arrhythmias (eg. CS ECG abnormalities, 2nd degree (Mobitz Type II) or 3rd degree AV block); history of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting within 3 months of Screening; heart failure NYHA III or IV class; uncontrolled hypertension.
6. Any major surgery within the last 4 weeks.
7. Any other active malignancy, except the disease is medically stable for at least 2 years or not require active therapy other than hormonal.
8. Known immediate or delayed hypersensitivity reaction or idiosyncratic reaction to belantamab mafodotin, drugs chemically related, or any of the components of the study treatment.
9. Evidence of active mucosal or internal bleeding.
10. Cirrhosis or current unstable liver or biliary disease assessed by Investigator. Stable non-cirrhotic chronic liver disease is acceptable if other entry criteria are met.
11. Intolerance or contraindications to anti-viral prophylaxis.
12. Active, uncontrolled bacterial, fungal, or viral infection. Active infections must be resolved at least 14 days prior to enrollment.
13. Known HIV infection, unless the participant can meet all of the following criteria:
1. Established ART for at least 4 weeks and HIV viral load \< 400 copies/mL within Screening Period.
2. CD4+ T-cell (CD4+) counts ≥350 cells/μL.
3. No history of AIDS-defining opportunistic infections within the last 12 months. NOTE: consideration must be given to ART and prophylactic antimicrobials that may have a drug-drug interaction and/or overlapping toxicities with belantamab mafodotin or other combination products as relevant.
14. Positive hepatitis C antibody test result or positive hepatitis C RNA test result at screening or within 3 months before the first dose of the study intervention, unless the participant can meet the following criteria:
1. RNA test negative.
2. Successful antiviral treatment (usually 8 weeks duration) is required, followed by a negative HCV RNA test after a washout period of at least 4 weeks.
15. Participants with hepatitis B will be excluded unless the patient is:
1. HBcAb+, HBsAg- with undetectable HBV DNA at screening.
2. HBsAg+ at screening or within 3 months before first study dose, but has undetectable HBV DNA, and a highly effective antiviral treatment started at least 4 weeks prior to first dose of study intervention.
16. Presence of active serious renal conditions (e.g., requiring dialysis or any other condition that could affect the participant's safety). Isolated proteinuria due to MM is acceptable if other criteria are fulfilled.
17. Ongoing Grade 3 or higher peripheral neuropathy or neuropathic pain
18. Active or history of venous thromboembolism within the past 3 months.
19. Contraindications to anti-thrombotic prophylaxis.
20. Current corneal disease except for mild punctate keratopathy.
21. Any serious and/or unstable pre-existing medical, psychiatric disorder or other conditions (also lab abnormalities) that could interfere with participant's safety, obtaining ICF or compliance to the study procedures.
22. Pregnant or lactating female.
