Isatuximab Plus Pomalidomide and Dexamethasone Association for Patients With AL Amyloidosis Not in VGPR or Better After Any Previous Therapy

Inclusion Criteria: 1. Age ≥ 18 2. Histologic diagnosis of AL amyloidosis; 3. Patients should have received at least one line with an alkylating agent and/or a PI, and Dexamethasone and not be in VGPR (or better) at the time of inclusion (patients who did not reach VGPR before, or patients in VGPR or better before but with a hematological relapse at the time of inclusion can be included); 4. Measurable hematologic disease: difference between involved and uninvolved FLC \> 50 mg/L with an abnormal k/l ratio; 5. Symptomatic organ involvement (heart, kidney, liver/GI tract, peripheral nervous system) (See Appendix 1); 6. Wash-out period of at least 4 weeks from previous antitumor therapy or any investigational treatment or 5 half-lives from previous antibodies, whichever is longer. 7. Adequate bone marrow function prior to 1st drug intake (C1D1), without transfusion or growth factor support within 5 days prior to 1st drug intake, defined as: * Absolute neutrophils count ≥ 1000/mm3, * Platelets ≥ 75000/mm3, * Hemoglobin ≥ 8.0 g/dL, 8. Adequate organ function defined as: * Serum ASAT or ALAT ≤ 3.0 X Upper Limit of the normal range (ULN), * Serum total bilirubin level \< 1.5 x ULN, unless for subjects with Gilbert's syndrome where the direct bilirubin should then be ≤ 2.0 x ULN. 9. ECOG status ≤ 2 10. Male participants must agree to use contraception during the intervention period and for at least 5 months after the last dose of IsaPd and refrain from donating sperm during this period. * Female participants are eligible to participate if they are not pregnant, not breastfeeding, and at least one of the following conditions applies: Not a Female of childbearing potential (FCBP), OR a FCBP who must have 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 4 weeks before initiation of treatment, during the intervention period and for at least 5 months after IsaPd treatment, * Female patients who are postmenopausal for at least 1 year before the screening visit, or are surgically sterile, or if they are of childbearing potential, agree to practice effective methods of contraception from the time of signing the informed consent through 30 days after the last dose of study drug, or agree to completely abstain from intercourse (serum pregnancy test must be performed for all women of childbearing potential at the beginning of each cycle during the study. In addition, a pregnancy test may be done at any time during the study at the discretion of the investigator if a subject misses a period or has unusual menstrual bleeding); 11. Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care. Exclusion Criteria: 1. Presence of non-AL amyloidosis 2. AL amyloidosis with isolated soft tissue involvement 3. Bone marrow plasma cells \>30% and clinically symptomatic multiple myeloma with lytic bone lesions 4. NT-proBNP \> 8500 ng/L and hs-troponin I \> 100 ng/L or hs-troponin T \> 50 ng/L (cardiac stage IIIb patients) 5. Repetitive ventricular arrhythmias on 24h Holter ECG despite anti-arrhythmic treatment sustained ventricular tachycardia, aborted ventricular fibrillation, atrioventricular nodal or sinoatrial nodal dysfunction with no pacemaker 6. Chronic atrial fibrillation with uncontrolled heart rate 7. Significant cardiac dysfunction; myocardial infarction within 12 months; unstable poorly controlled angina pectoris 8. Uncorrected valvular disease unrelated to AL amyloid cardiomyopathy 9. QT interval as corrected by Fridericia's formula \>550 msec without pacemaker, 10. Undergoing dialysis 11. Ongoing toxicity (excluding alopecia and those listed in eligibility criteria) from any prior therapy \>G1 (NCI-CTCAE v5.0) 12. Supine systolic blood pressure \<90 mm Hg, or symptomatic orthostatic hypotension, defined as a decrease in systolic blood pressure upon standing of \<80 mmHg despite medical management (i.e. midodrine, fludrocortisones) in the absence of volume depletion 13. Previous anti-CD38 therapy or Pomalidomide therapy (if refractory to Pomalidomide) 14. Hypersensitivity to IMiD® defined as any hypersensitivity reaction leading to stop IMiD® within the 2 first cycles or toxicity, which does meet intolerance definition 15. Hypersensitivity or history of intolerance to steroids, mannitol, pregelatinized starch, sodium stearyl fumarate, histidine (as base and hydrochloride salt), arginine hydrochloride, polysorbate 80, poloxamer 188, sucrose or any of the other components of study treatment that are not amenable to premedication with steroids and H2 blockers or would prohibit further treatment with these agents 16. History of malignancy (other than AL amyloidosis) within 3 years before the date of inclusion (exceptions are squamous and basal cell carcinomas of the skin, carcinoma in situ of the cervix or breast, or other non-invasive lesion that in the opinion of the investigator, with concurrence with the sponsor's medical monitor, is considered cured with minimal risk of recurrence within 3 years) 17. Any clinically significant, uncontrolled medical conditions that, in the Investigator's opinion, would expose the patient to excessive risk or may interfere with compliance or interpretation of the study results 18. Active systemic infection and severe infections requiring treatment with a parenteral administration of antibiotics 19. Received any investigational drug within 14 days or 5 half-lives of the investigational drug prior to initiation of study intervention, whichever is longer. In case of very aggressive disease (i.e acute leukemia) delay could be shortened after agreement between sponsor and investigator, in absence of residual toxicities from previous therapy 20. Known positive for HIV or active hepatitis A, B or C: * Uncontrolled or active HBV infection: Patients with positive HBsAg and/or HBV DNA Of note: Patient can be eligible if anti-HBc IgG positive (with or without positive anti-HBs) 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. * Active HCV infection: positive HCV RNA and negative anti-HCV. Of note: 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 21. Pregnant or breast-feeding females