Inclusion Criteria:

* For inclusion in the trial, all the following inclusion criteria must be fulfilled, as no waivers will be permitted:

Voluntarily agree to participate by giving written informed consent

≥18 years of age

Histologically confirmed multiple myeloma that has relapsed from, is considered refractory to, or is intolerant to regimens containing any of the following:

A proteasome inhibitor

An immunomodulating agent

A CD38-monoclonal antibody

Measurable disease, defined as one of the following:

M-protein ≥ 0.5g/dL (0.3 g/dL or above if IgA subtype)

Urine M-protein ≥ 200 mg/24hours

Serum free light chain difference \> 100 mg/L

Serum free light chain ratio (involved/uninvolved) ≥ 8

Biopsy proven plasmacytoma

Bone marrow involvement \>10%

ECOG performance status of 0-2

Adequate organ function, as indicated by the following laboratory values:

Adequate hematological function, defined as ANC ≥ 1000/µL, platelet count ≥ 75,000/µL, and hemoglobin ≥ 8 g/dL (transfusion and/or growth factor support is allowed for hematologic parameters as long as the investigator deems the patient otherwise fit for screening)

Adequate hepatic function, defined as total bilirubin level ≤ 1.5 x institutional upper limit of normal (IULN) except in participants with congenital bilirubinemia, such as Gilbert syndrome (in which case direct bilirubin ≤1.5 x IULN is required), AST ≤ 2.5 x IULN, and ALT ≤ 2.5 x IULN

Adequate renal function, defined as calculated creatinine clearance ≥ 30 mL/min per institutional standard (assessment method should be recorded, measured or C-G acceptable)

Adequate coagulation, defined as international normalized ratio (INR) or prothrombin time ≤ 1.5 x IULN and activated partial thromboplastin time (aPTT) ≤ 1.5 x IULN (unless patient is receiving anticoagulant therapy)

Persons of childbearing potential must have a negative serum pregnancy test at screening (within 72 hours of first dose of trial medication). Non-childbearing potential for a person assigned as female at birth is defined as 1 of the following:

≥ 45 years of age and has not had menses for \>1 year

Amenorrheic for \> 2 years without a hysterectomy and/or oophorectomy and follicle-stimulating hormone value in the postmenopausal range upon pretrial (screening) evaluation

Status is post-hysterectomy, -oophorectomy, or -tubal ligation

Persons of childbearing potential must be willing to use highly effective contraceptive measures during sexual contact with a person assigned as male at birth starting with the Screening visit through 90 days after last dose of trial treatment.

Note: Abstinence is acceptable if this is the established and preferred contraception for the participant.

Persons assigned as male at birth with a partner(s) of childbearing potential must agree to use highly effective contraceptive measures throughout the trial starting with the Screening visit through 90 days after the last dose of trial treatment is received. Persons assigned as male at birth with pregnant partners must agree to use a condom; no additional method of contraception is required for the pregnant partner.

Note: Abstinence is acceptable if this is the established and preferred contraception method for the participant.

Known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using New York Heart Association Functional Classification. To be eligible for this trial, patients should be Class 2 or lower. Class 2 is defined as slight limitation of physical activity, in which ordinary physical activity leads to fatigue, palpitation, or dyspnea; the person is comfortable at rest.

Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessments of the investigational arms are eligible for this trial.

Patients with known HIV infection who are on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.

Patients with evidence of chronic hepatitis B virus (HBV) infection must have an undetectable HBV viral load on suppressive therapy, if indicated.

Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with known HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.

Willing and able to comply with the requirements of the protocol.

Exclusion Criteria:

* For inclusion in the trial, all the following inclusion criteria must be fulfilled, as no waivers will be permitted:

Voluntarily agree to participate by giving written informed consent

≥18 years of age

Histologically confirmed multiple myeloma that has relapsed from, is considered refractory to, or is intolerant to regimens containing any of the following:

A proteasome inhibitor

An immunomodulating agent

A CD38-monoclonal antibody

Measurable disease, defined as one of the following:

M-protein ≥ 0.5g/dL (0.3 g/dL or above if IgA subtype)

Urine M-protein ≥ 200 mg/24hours

Serum free light chain difference \> 100 mg/L

Serum free light chain ratio (involved/uninvolved) ≥ 8

Biopsy proven plasmacytoma

Bone marrow involvement \>10%

ECOG performance status of 0-2

Adequate organ function, as indicated by the following laboratory values:

Adequate hematological function, defined as ANC ≥ 1000/µL, platelet count ≥ 75,000/µL, and hemoglobin ≥ 8 g/dL (transfusion and/or growth factor support is allowed for hematologic parameters as long as the investigator deems the patient otherwise fit for screening)

Adequate hepatic function, defined as total bilirubin level ≤ 1.5 x institutional upper limit of normal (IULN) except in participants with congenital bilirubinemia, such as Gilbert syndrome (in which case direct bilirubin ≤1.5 x IULN is required), AST ≤ 2.5 x IULN, and ALT ≤ 2.5 x IULN

Adequate renal function, defined as calculated creatinine clearance ≥ 30 mL/min per institutional standard (assessment method should be recorded, measured or C-G acceptable)

Adequate coagulation, defined as international normalized ratio (INR) or prothrombin time ≤ 1.5 x IULN and activated partial thromboplastin time (aPTT) ≤ 1.5 x IULN (unless patient is receiving anticoagulant therapy)

Persons of childbearing potential must have a negative serum pregnancy test at screening (within 72 hours of first dose of trial medication). Non-childbearing potential for a person assigned as female at birth is defined as 1 of the following:

≥ 45 years of age and has not had menses for \>1 year

Amenorrheic for \> 2 years without a hysterectomy and/or oophorectomy and follicle-stimulating hormone value in the postmenopausal range upon pretrial (screening) evaluation

Status is post-hysterectomy, -oophorectomy, or -tubal ligation

Persons of childbearing potential must be willing to use highly effective contraceptive measures during sexual contact with a person assigned as male at birth starting with the Screening visit through 90 days after last dose of trial treatment.

Note: Abstinence is acceptable if this is the established and preferred contraception for the participant.

Persons assigned as male at birth with a partner(s) of childbearing potential must agree to use highly effective contraceptive measures throughout the trial starting with the Screening visit through 90 days after the last dose of trial treatment is received. Persons assigned as male at birth with pregnant partners must agree to use a condom; no additional method of contraception is required for the pregnant partner.

Note: Abstinence is acceptable if this is the established and preferred contraception method for the participant.

Known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using New York Heart Association Functional Classification. To be eligible for this trial, patients should be Class 2 or lower. Class 2 is defined as slight limitation of physical activity, in which ordinary physical activity leads to fatigue, palpitation, or dyspnea; the person is comfortable at rest.

Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessments of the investigational arms are eligible for this trial.

Patients with known HIV infection who are on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.

Patients with evidence of chronic hepatitis B virus (HBV) infection must have an undetectable HBV viral load on suppressive therapy, if indicated.

Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with known HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.

Willing and able to comply with the requirements of the protocol.

For inclusion in the trial, patients will not be eligible to participate in Horizon if any of the following criteria are met, as no waivers will be permitted:

Major concurrent illness or organ dysfunction including but not limited to the following:

Plasma cell leukemia (the presence of ≥5% circulating plasma cells in peripheral blood smears)

Waldenström's macroglobulinemia

POEMS syndrome

primary light-chain amyloidosis

History of allergy or known hypersensitivity to any of the trial treatments or any of their excipients, or contraindication to any of the trial treatments as outlined in the local prescribing information (e.g., United States Prescribing Information \[USPI\]).

Complete spinal cord compression or CNS involvement

Allogeneic tissue/solid organ transplant recipients with chronic GVHD requiring steroid equivalent dose of \> 20 mg prednisone

Active infection requiring treatment

History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or is not in the best interest of the patient to participate, in the opinion of the treating investigator

Psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the trial

Legally incapacitated or has limited legal capacity

Persons who are pregnant or lactating