Isatuximab and Bendamustine in Systemic Light Chain Amyloidosis

Inclusion Criteria: 1. Age ≥ 18 2. Histopathologically confirmed AL amyloidosis based on detection by polarizing microscopy of green birefringent material in Congo Red stained tissue specimens or characteristic electron microscopy appearance or immunohistohemical stain with anti-light chain anti-sera. Diagnosis cannot be based solely on congo red stain on bone marrow biopsy. 3. Measurable disease (one of the following): 1. Serum monoclonal protein ≥ 0.5g/dL 2. Urine monoclonal protein \>200mg/dL in 24 hour urine collection 3. Clonal population of plasma cells in the bone marrow 4. dFLC \> 40mg/L 4. Mayo Cardiac Amyloid Stage I-IIIA based on the Mayo 2004/European Addition criteria 5. ECOG 0-2 6. ANC ≥ 1.0 x10\^9/L 7. Hemoglobin ≥ 8g/dL 8. Platelet count ≥ 75 x10\^9/L 9. Calculated creatinine clearance ≥ 30mL/min based on the Cockcroft-Gault formula 10. AST and ALT ≤ 2.5x ULN 11. Serum bilirubin \< 1.5x ULN 12. Willingness to provide consent and participate in study activities 13. Male participants must agree to use contraception during the intervention period and for at least 5 months after the last dose of isatuximab treatment and refrain from donating sperm during this period. 14. Female participants may not be pregnant, not be breastfeeding, and at least one of the following conditions apply: 1. Not a female of childbearing potential 2. A female of childbearing potential who has a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10 - 14 days prior to and again within 24 hours prior to starting study medication and before each cycle of study treatment and must either commit to continue abstinence from heterosexual intercourse or apply a highly effective method of birth control during the intervention period and for at least 5 months after the last dose of isatuximab treatment Exclusion Criteria: 1. Resistant to prior anti CD38 antibody therapy as defined as either non-responsive or progression while on or within 60 days of discontinuation of treatment 2. Received anti CD38 antibody in the previous 6 months 3. Active symptomatic multiple myeloma as defined by IMWG. Smoldering multiple myeloma is permissible. 4. Myocardial infarction within 6 months prior to enrollment. 5. NYHA class IIIB or IV heart failure 6. Mayo Cardiac Amyloid Stage IIIB based on the Mayo 2004/European Addition criteria (See Appendix A) 7. Uncontrolled angina 8. Severe uncontrolled ventricular arrhythmias 9. Active conduction system abnormalities not including 1st degree AV-block, Wenckebach type 2nd degree heart block, or left bundle branch block. 10. Use of other investigational drug within 14 days or 5 half-lives of the investigational drug prior to initiation of study intervention, whichever is longer. 11. Any clinically significant, uncontrolled medical condition that, in the investigator's opinion, would expose the patient to excessive risk or may interfere with compliance or interpretation of the study results. 12. Active systemic infection and severe infections requiring treatment with parenteral administration of antibiotics. 13. Known to be HIV+ or to have hepatitis A, B, or C active infection 1. Uncontrolled or active HBV infection: Patients with positive HBsAg and/or HBV DNA * Patients can be eligible if anti-HBc IgG positive (with or without positive antiHBs) but HBsAg and HBV DNA are negative. * If anti-HBV therapy in relation with prior infection was started before initiation of IMP, the anti-HBV therapy and monitoring should continue throughout the study treatment period. * Patients with negative HBsAg and positive HBV DNA observed during screening period will be evaluated by a specialist for start of anti-viral treatment: study treatment could be proposed if HBV DNA becomes negative and all the other study criteria are still met. 2. Active HCV infection: positive HCV RNA and negative anti HCV * Patients with antiviral therapy for HCV started before initiation of IMP and positive HCV antibodies are eligible. The antiviral therapy for HCV should continue throughout the treatment period until seroconversion. * Patients with positive anti-HCV and undetectable HCV RNA without antiviral therapy for HCV are eligible. 14. Pregnancy or breastfeeding 15. Treatment or diagnosis of another malignancy within 3 years of enrollment except complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, low risk prostate cancer. 16. Hypersensitivity to bendamustine 17. Hypersensitivity or history of intolerance to steroids, mannitol, pregelatinized starch, sodium stearyl fumarate, histidine (as base and hydrochloride salt), arginine hydrochloride, poloxamer 188, sucrose or any of the other components of study intervention that are not amenable to premedication with steroids and H2 blockers or would prohibit further treatment with these agents.