Isatuximab for the Treatment of Monoclonal Gammopathy of Renal Significance

Inclusion Criteria

• Renal biopsy proven diagnosis of an MGRS disorder including one of the following: * Proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) * C3 glomerulopathy associated with monoclonal gammopathy ** A concurrent diagnosis of monoclonal gammopathy (with positive [+ve] serum and/or urine protein electrophoresis or bone marrow biopsy) is required in patients with C3 glomerulopathy but not for other disorders. Patients with concurrent MGUS, non-high risk smoldering myeloma are eligible for enrollment
• Measurable proteinuria >= 1 gram over 24 hours
• Prior therapy: Newly diagnosed as well as patients with previous therapy but persistent renal dysfunction and persistent proteinuria >= 1 gram over 24 hours are eligible for enrollment. Patients who received a prior CD38 antibody therapy are not eligible for study. In patients who have received prior therapy a wash out period of 12 weeks for chemotherapy based therapies and 24 weeks for rituximab based therapies is required between completion of prior therapy and cycle 1 day 1 of study therapy
• Age >= 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2
• Life expectancy of greater than 6 months
• Leukocytes >= 3,000/mcL
• Absolute neutrophil count >= 1,500/mcL
• Platelets >= 100,000/mcL
• Total bilirubin within normal institutional limits
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal
• Estimated glomerular filtration rate (eGFR) >= 30 mL/min/1.73 m^2

Exclusion Criteria

• Participants who have had chemotherapy based therapy within 12 weeks or rituximab based therapy within prior 24 weeks prior to starting the cycle 1 day 1 of trial therapy
• Participants who are receiving any other investigational agents concurrently
• History of severe allergic reactions or anaphylaxis attributed to compounds of similar chemical or biologic composition to isatuximab
• Diagnosis of multiple myeloma or high risk smoldering multiple myeloma or a B cell lymphoma meeting criteria for therapy
• Renal biopsy showing the coexistence of other significant diagnosis e.g. advanced diabetic nephropathy. If the concurrent diagnosis such as diabetic or hypertensive nephropathy are mild on renal biopsy and MGRS lesions is the predominant pathology, patient can be enrolled on the study after discussion with the principal investigator (PI)
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant and lactating women are excluded from this study because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with isatuximab. Females of childbearing potential (FCBP) must have a negative baseline pregnancy test within 14 days prior to registration. This may be either a serum or urine pregnancy test, with a sensitivity of at least 50 mIU/mL. FCBP must also agree to have a pregnancy test prior to the start of each treatment cycle. FCBP or male subjects with female partners of childbearing potential shall be required to use highly effective contraceptive methods (a failure of < 1% per year when used consistently and correctly) starting 2 weeks before first isatuximab administration, while on therapy and for 5 months following the last dose of isatuximab. A woman is considered of childbearing potential, ie fertile, following menarche and until becoming post- menopausal unless permanently sterile. The following highly effective methods of contraception are accepted: * Oral, intravaginal, or transdermal hormonal contraception associated with inhibition of ovulation * Placement of an intrauterine device or intrauterine hormone-releasing system * Bilateral tubal ligation, Hysterectomy or bilateral oophorectomy * Sexual abstinence during the entire period of risk associated with study treatments
• Men must agree to use a condom with either cap, diaphragm or sponge with spermicide (double barrier method) during sexual contact with a FCBP, even if they have had a successful vasectomy starting 2 weeks before first isatuximab administration, while on therapy and for 5 months following the last dose of isatuximab
• Human immunodeficiency virus (HIV)-positive participants are ineligible because of increased risk of lethal infections when treated with immunosuppressive therapy