Has a previous or current diagnosis of plasma cell dyscrasia with POEMS syndrome or symptomatic MM
Has IgM-related AL amyloidosis
Has any form of non-AL amyloidosis, including wild type or mutated (ATTR) amyloidosis.
Has evidence of significant CV conditions as specified below:
NYHA classification IIIb or IV heart failure.
Heart failure that in the opinion of the investigator is caused by ischemic heart disease (e.g., prior myocardial infarction with documented history of cardiac enzyme elevation and ECG changes) or uncorrected valvular disease and not primarily due to AL amyloidosis cardiomyopathy.
In-patient admission to a hospital for unstable angina or myocardial infarction within the last 3 months prior to screening or percutaneous cardiac intervention with recent stent within last 3 months prior to screening or coronary artery bypass grafting within the last 3 months prior to screening.
Participants with a current evidence of clinically significant untreated arrhythmia(s), including clinically significant ECG abnormalities including second-degree (Mobitz Type II) or third-degree atrioventricular block
Participants with a history of sustained ventricular tachycardia or aborted ventricular fibrillation or with a history of atrioventricular nodal or sinoatrial nodal dysfunction for which a pacemaker/implantable cardioverter-defibrillator is indicated but not placed (participants who do have a pacemaker/implantable cardioverter-defibrillator are allowed on the study).
Screening 12-lead ECG showing a baseline QT interval as corrected by Fridericia’s formula (QTcF) >500 msec. Participants who have a pacemaker may be included regardless of calculated QTc interval
Supine systolic blood pressure <90 mm Hg, or symptomatic orthostatic hypotension, defined as a decrease in systolic blood pressure upon standing of >20 mmHg despite medical management (e.g., midodrine, fludrocortisones) in the absence of volume depletion
Uncontrolled hypertension.
Has Mayo stage 3B disease
Has a current corneal epithelial disease except for mild punctate keratopathy.
Has previous or concurrent malignancies other than AL amyloidosis, except for any other malignancy that has been considered medically stable for at least 2 years, after discussion with GSK medical monitor. The participant must not be receiving active therapy, other than hormonal therapy for this disease.
Has major surgery within 2 weeks prior to the first dose of study interventions or has not recovered fully from surgery.
Has any history of prior allogenic or autologous BM transplant or other solid organ transplant.
Has known immediate or delayed hypersensitivity reaction or idiosyncratic reaction to drugs chemically related to belantamab mafodotin, cyclophosphamide, bortezomib, boron or mannitol or any other components or excipients or other allergy that, in the opinion of the investigator or GSK medical monitor, contraindicates participation in the study.
Has any serious and/or unstable medical or psychiatric disorder or other condition(s) (including laboratory assessment abnormalities) that could interfere with the participant’s safety, obtaining of informed consent, or compliance with the study procedures.
Has active infection or active bleeding
Has intolerance or contraindications to antiviral prophylaxis.
Has known HIV infection, unless the participant can meet all of the following criteria:
Established ART for at least 4 weeks and HIV viral load <400 copies/mL within the screening period.
CD4+ T-cell (CD4+) counts ≥350 cells/μL.
No history of AIDS-defining opportunistic infections within the last 12 months.
Has prior therapy for AL amyloidosis or MM, with the exception of 160 mg dexamethasone (or equivalent corticosteroid) maximum exposure prior to enrollment.
Has received any live or live-attenuated vaccine within 30 days prior to first dose of belantamab mafodotin.
] Is currently enrolled or has participated in any other clinical study involving an investigational study intervention or any other type of interventional medical research within 28 days before enrollment.
Has an ALT value >2.5×ULN or >3xULN if hepatic involvement of AL amyloidosis
Has a total bilirubin value >1.5×ULN.
Has cirrhosis or current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal/gastric varices, or persistent jaundice.
Has documented presence of HBsAg and/or HBcAb at screening or within 3 months prior to the first dose of study intervention
Has a 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 intervention unless the participant can meet the following criteria: