Belantamab Mafadotin Maintenance Therapy After Salvage Autologous Hematopoietic Cell Transplantation in Patients With Relapse Refractory Multiple Myeloma

Inclusion Criteria:

1. Patients with relapsed or refractory multiple myeloma. Eligible patients will beenrolled in the protocol no less than 60 days and must be initiated no longer than 180 days (± 2 weeks) post ASCT. Patient's transplant may be either transplantationnaïve or with a history of previous autologous transplant.

2. Patients who have had two or more lines of therapy consisting of at least one ofthree agents including a proteasome inhibitor or an immunomodulatory agent or ananti-CD38 targeting therapy. Note: a) Induction therapy, autologous stem cell transplantation (ASCT) & maintenancetherapy if given sequentially without intervening progressive disease (PD) areconsidered one line of therapy. b) Refractory MM may be defined as disease that isrefractory to treatment while on therapy or that shows progression within 60 days ofthe last therapy.

3. Disease status, partial response, or better.

4. Age ≥ 18-year and ≤ 75-year. English and non-English speaking patients are eligible.

5. Platelet count ≥ 50,000/mm3 & Hemoglobin ≥ 8 g/dL, ANC ≥ 1.0 × 109/L

6. Karnofsky Performance Status (KPS) >70 (Appendix B.).

7. Adequate organ function (ALT ≤ 2.5 ULN; Total bilirubin ≤ 1.5 ULN or total bilirubin

• 1.5 ULN with direct bilirubin ≤ 35%; estimated glomerular filtration rate ≥30mL/min per 1.73 m2

8. Participants must not be pregnant or lactating

9. Female participants: contraceptive use should be consistent with institutionalguidelines regarding the methods of contraception for those participating inclinical studies.

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 failurerate of <1% per year), preferably with low user dependency (as described in AppendixC.), during the intervention period and for at least 4 months after the last dose ofstudy intervention and agrees not to donate eggs (ova, oocytes) for reproductionduring this period. The investigator should evaluate the effectiveness of thecontraceptive method in relation to the first dose of the study intervention. A WOCBP must have a negative highly sensitive serum pregnancy test (as required bylocal regulations) within 72 hours before the first dose of the study intervention. Nonchildbearing potential is defined as follows (by other than medical reasons):

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

• Patients who have been amenorrhoeic for <2 years without a history of ahysterectomy and oophorectomy must have a follicle-stimulating hormone value in thepostmenopausal range upon screening evaluation

• Post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation. 10. Maleparticipants: contraceptive use should be consistent with institutional guidelinesregarding the methods of contraception for those participating in clinical studies. Male participants are eligible to participate if they agree to the following duringthe intervention period and for 6 months after the last dose of study treatment toallow for clearance of any altered sperm:

• Refrain from donating sperm PLUS either:

• Be abstinent from heterosexual intercourse as their preferred and usuallifestyle (abstinent on a long term and persistent basis) and agree to remainabstinent. OR

• Must agree to use contraception/barrier as detailed below: Agree to use a malecondom, even if they have undergone a successful vasectomy and female partner to usean additional highly effective contraceptive method with a failure rate of <1% peryear as to when having sexual intercourse with a woman of childbearing potential whois not currently pregnant.

Exclusion Criteria:

1. Current corneal epithelial disease (except mild punctate keratopathy). 2.Participant must not use contact lenses while participating in this study. 3.Ongoing Grade 2 or higher peripheral neuropathy or neuropathic pain. 4.Participants who are using an investigational drug or approved systemicanti-myeloma therapy (including systemic steroids) within 14 days or fivehalf-lives, whichever is shorter, preceding the first dose of study drug.

2. Participants who have current unstable liver or biliary disease defined by thepresence of ascites, encephalopathy, coagulopathy, hypoalbuminemia (serumalbumin < 3.0 gm/dl), esophageal or gastric varices, persistent jaundice, orcirrhosis. Note: Stable non-cirrhotic chronic liver disease (includingGilbert's syndrome or asymptomatic gallstones) or hepatobiliary involvement ofmalignancy is acceptable if otherwise meets entry criteria 6. Participants whohave presence of active renal condition (infection, requirement for dialysis orany other condition that could affect participant's safety). Participants withisolated proteinuria resulting from MM are eligible, provided they fulfilinclusion criteria 7. Participants who have received prior treatment with amonoclonal antibody within 30 days of receiving the first dose of study drugs.

3. Participants who have had major surgery ≤ 4 weeks before initiating studytreatment.

4. Participants who have any evidence of active mucosal or internal bleeding. 10.Participants who have known immediate or delayed hypersensitivity reaction oridiosyncratic reactions to belantamab mafodotin or drugs chemically related tobelantamab mafodotin, or any of the components of the study treatment.

5. Participants who have an active infection requiring treatment 12. Participantswho have evidence of cardiovascular risk, including any of the following:

a) Evidence of current clinically significant uncontrolled and/or untreated arrhythmias, including clinically significant ECG abnormalities such as 2nd degree (Mobitz Type II) or 3rd degree atrioventricular (AV) block.

b) History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting within three (3) months of screening.

c) Class III or IV heart failure as defined by the New York Heart Association functional classification system.

d) Uncontrolled hypertension. 13. Participants who have known HIV infection, unless the participant can meet all of the following criteria:

• Established anti-retroviral therapy (ART) for at least 4 weeks and HIV viral load <400 copies/mL

• CD4+ T-cell (CD4+) counts ≥350 cells/uL

• No history of AIDS-defining opportunistic infections within the last 12 months 14.Participant must not have presence of hepatitis B surface antigen (HBsAg), orhepatitis B core antibody (HBcAb) at screening or within 3 months prior to firstdose of study treatment. Note: presence of Hep B surface antibody (HBsAb) indicatingprevious vaccination will not exclude a participant.

15. Participant must not have positive hepatitis C antibody test result or positivehepatitis C RNA test result at screening or within 3 months prior to first doseof study treatment.

Note: Participants with positive Hepatitis C antibody due to prior resolved disease can be enrolled, only if a confirmatory negative Hepatitis C RNA test is obtained.

Note: Hepatitis RNA testing is optional and participants with negative Hepatitis C antibody test are not required to also undergo Hepatitis C RNA testing.

16. Participant must not have invasive malignancies other than disease under study,unless the second malignancy has been medically stable for at least 2 years and, inthe opinion of the principal investigators, will not affect the evaluation of theeffects of clinical trial treatments on the currently targeted malignancy.Participants with curatively treated non-melanoma skin cancer may be enrolledwithout a 2-year restriction.

17. Prior allogeneic stem cell transplant. NOTE: Participants who have undergonesyngeneic transplant will be allowed only if no history of or no currently activeGvHD.

18. Symptomatic amyloidosis, active POEMS syndrome (polyneuropathy, organomegaly,endocrinopathy, monoclonal plasmaproliferative disorder, skin changes) or activeplasma cell leukaemia at the time of screening.

19. Patients with cognitive impairments and/or any serious unstable pre-existing medicalcondition or psychiatric disorder that can interfere with safety or with obtaininginformed consent or compliance with study procedures. Informed Consent Process. Theinformed consent process will begin at recognition of subject eligibility, andconsent will be obtained per Institutional practices before study therapy isinitiated.