Isatuximab, Velcade, and Dexamethasone in Patients With Multiple Myeloma and Severe KIDNEY Disease

Inclusion Criteria: This study will enroll 28 evaluable patients. Fourteen (+/- 2) patients will be requiredtto be on dialysis and 14 (+/- 2) patients will not be on dialysis.

• Newly diagnosed multiple myeloma diagnosis according to IMWG criteria. Patientseligible for autologous stem cell transplant may be enrolled if the intent is toproceed to transplant after 4 or more cycles of study treatment.
• Severe renal impairment (eGFR < 30ml/min/1.73m^2 using the MDRD calculator) or ondialysis. The value at screening confirms eligibility (if eGFR improves prior toenrollment, this does not render a patient ineligible) The renal impairment may beacute or chronic and may be related to the underlying myeloma (e.g. multiple myeloma (MM) cast nephropathy, monoclonal immunoglobulin deposition disease [MIDD], myelomacell infiltration) or another cause (e.g. diabetes, hypertension), however theacuity/chronicity and the underlying cause should be documented clearly. Those whohave acute kidney injury from hypercalcemia should receive intravenous hydration andcalcium-lowering therapy to see if this renal impairment is reversible.
• At least 18 years of age.
• ECOG performance status ≤ 2
• Bone marrow and organ function as defined below:
• Absolute neutrophil count ≥ 1,000/mm3 (growth factor to achieve this level ispermissible)
• Platelets ≥ 50,000/mm3 (transfusion to achieve this level is permissible)
• Bilirubin ≤ 2 mg/dL
• AST(SGOT)/ALT(SGPT) ≤ 3.5 x institutional upper limit of normal (IULN)
• The effects of isatuximab and bortezomib on the developing human fetus are unknown.For this reason, women of childbearing potential must agree to use adequatecontraception (hormonal or barrier method of birth control, abstinence) prior to studyentry, for the duration of study participation, and for 5 months after discontinuationof study treatment. Should a woman become pregnant or suspect she is pregnant whileparticipating in this study, she must inform her treating physician immediately. Mentreated or enrolled on this protocol must also agree to use adequate contraceptionprior to the study, for the duration of the study, and 5 months after completion ofthe study
• Ability to understand and willingness to sign an IRB approved written informed consentdocument (or that of legally authorized representative, if applicable).

Exclusion Criteria:

• Concomitant use of other anti-neoplastic medications or radiotherapy (except forlocalized disease). Note: Participants are permitted to have received one dose ofbortezomib or up to 80 mg of dexamethasone (or equivalent) prior to study treatmentinitiation if deemed clinically necessary for disease control.
• Currently receiving any other investigational agents.
• Evidence of myeloma within the CNS
• Presence of amyloidosis without concomitant multiple myeloma. Patients withconcomitant amyloidosis and multiple myeloma are eligible.
• Prior refractoriness, intolerance or hypersensitivity to bortezomib.
• Prior treatment with an anti-CD38 monoclonal antibody.
• A history of allergic reactions attributed to compounds of similar chemical orbiologic composition to isatuximab, bortezomib, or dexamethasone or other agents usedin the study.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or activeinfection, symptomatic congestive heart failure, unstable angina pectoris, or cardiacarrhythmia.
• Pregnant and/or breastfeeding. Women of childbearing potential must have a negativepregnancy test within 14 days of study entry.
• Active acute or chronic hepatitis B viral infection.
• Screening with serological tests for HBV with surface antigen and antibody (HBsAgand HBsAb) and HBV total core antibody (HBcAb IgG and IgM), and screening for HCV (HCV Ab and HCV RNA level) are required to have been performed within 1 year ofscreening, or should otherwise be performed as part of screening.
• Patients with uncontrolled or active HBV infection (patients with positive HBsAgand/or HBV DNA), as well as patients with active HCV infection (positive HCV RNAand negative anti-HCV) are not eligible
• In case HBcAb are positive, HBV DNA testing by polymerase chain reaction willalso be done at baseline. For patients with positive anti-HBc IgG, negative HBsAgand undetectable (under limit of quantification) HBV DNA at study entry (HBVcarriers: past resolved infection, resolving acute infection or receivingantiviral treatment with controlled infection), specialist advice may berequested, close monitoring of viral reactivation throughout and following theend of study treatment should be proposed (alanine aminotransferase, aspartateaminotransferase, and HBV DNA at least every 3 months, up to 6 months aftertreatment discontinuation or initiation of further anticancer therapy.
• Patients with HIV are eligible unless their CD4+ T-cell counts are < 350 cells/mcL orthey have a history of AIDS-defining opportunistic infection within the 12 monthsprior to registration. Concurrent treatment with effective ART according to DHHStreatment guidelines is recommended.
• Baseline Grade 2 or higher peripheral neuropathy