Isatuximab, Carfilzomib, Pomalidomide, and Dexamethasone for the Treatment of Relapsed or Refractory Multiple Myeloma

Inclusion Criteria:

Patients with relapsed or refractory multiple myeloma, with >= 1 prior therapy
Must have received prior lenalidomide therapy

Must have measurable disease, as defined by International Myeloma Working Group criteria, having one or more of the following:

Serum M protein >= 0.5 g/dL
Urine M protein >= 200 mg/24 hours
Involved serum free light chain level >= 10 mg/dL with abnormal kappa/lambda ratio
Measurable biopsy-proven plasmacytomas (>= 1 lesion has a single diameter >= 2 cm)
Bone marrow plasma cells >= 30%
Age 18 years and older, and have the capacity to give informed consent
Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
Subjects should have resolution of any toxicities from prior therapy to grade =< 1 or baseline prior to enrollment (with the exception of peripheral neuropathy)
Subjects are required to have grade =< 2 peripheral neuropathy to enroll
Prior autologous stem cell transplant is allowed; patients must be >= 6 months post- autologous stem cell transplantation to enroll
Estimated glomerular filtration rate (eGFR) >= 20 ml/min
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x upper limit of normal (ULN)
Total bilirubin =< 2 x ULN
Absolute neutrophil count (ANC) >= 1,000/uL
Platelets >= 50,000/uL
Hemoglobin >= 8 g/dL
Growth factor use or transfusions may be used to meet the eligibility requirement for ANC, platelets, and hemoglobin
Female patients of childbearing potential and male patients must agree to use 2 effective forms of contraception or continuously abstain from heterosexual intercourse during the period of therapy, and for 6 months after discontinuation of study treatment for females and 3 months after discontinuation of study treatment for males

Exclusion Criteria:

History of clinically significant cardiovascular disease, including congestive heart failure New York Heart Association (NYHA) class 3-4, symptomatic ischemia, left ventricular ejection fraction < 40%, uncontrolled conduction abnormalities, myocardial infarction in last 6 months
Uncontrolled hypertension as determined by the principal investigator (PI) or designee
Active plasma cell leukemia or systemic amyloid light-chain (AL) amyloidosis
History of another primary malignancy that has not been in remission for at least 1 year (with the exception of non-melanoma skin cancer, curatively treated localized prostate cancer, curatively treated superficial bladder cancer and cervical carcinoma in site on biopsy or a squamous intraepithelial lesion on papanicolaou [PAP] smear)
For patients with chronic hepatitis B viral infection, the hepatitis B virus (HBV) polymerase chain reaction (PCR) must be undetectable on suppressive therapy
Patients with a history of Hepatitis C viral infection must have been treated and cured. For patients on treatment for hepatitis C, they are eligible if they have an undetectable hepatitis C virus (HCV) viral load
Subjects with active uncontrolled infection
Concurrent use of other anticancer agents or experimental treatments
Treatment with anti-CD38 monoclonal antibody therapy in the last 90 days