Venetoclax-Dexamethasone in Relapsed and/or Refractory t(11;14) Amyloidosis

Inclusion Criteria:

• Age ≥ 18 years at time of signing Informed Consent Form

• Ability to comply with the study protocol, in the investigator's judgment

• Confirmed diagnosis of systemic AL amyloidosis by mass spectrometry orimmunohistochemistry (IHC) on a tissue biopsy

• Has received ≥1 prior lines of therapy, including an anti-cluster of differentiation 38 (CD 38) monoclonal antibody

• Participants with a history of autologous hematopoietic cell transplantation musthave recovered from any transplant-related toxicities

• Presence of t(11;14) on FISH at any time since diagnosis (Eligibility must confirmedby FISH testing at Columbia University Irving Medical Center (CUIMC)

• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2

Exclusion Criteria:

• Known hypersensitivity to any of the study drugs

• History of other malignancy that could affect compliance with the protocol orinterpretation of results (Patients with a history of curatively treated basal orsquamous cell carcinoma of the skin, in situ carcinoma of the cervix, breast cancer,or Hodgkin's Lymphoma are generally eligible. Patients with a malignancy that hasbeen treated, but not with curative intent, will be excluded, unless the malignancyhas been in remission without treatment for ≥ 2 years prior to enrollment.)

• Evidence of other clinically significant uncontrolled condition(s) including, butnot limited to, uncontrolled systemic infection (viral, bacterial, or fungal)

• Patients on renal replacement therapy

• Known GI disease or GI procedure that could interfere with oral absorption (including difficulty swallowing)

• New York Heart Association (NYHA) Class III or IV heart failure

• Mayo stage three-B (IIIB) with N-terminal pro-hormone B-type natriuretic peptide (NT-Pro BNP) > 8500 pg/mL

• Prior exposure to anti-apoptotic protein B-cell lymphoma 2 (BCL-2) inhibitors

• Patients with human immunodeficiency virus (HIV) who are not on highly activeantiretroviral therapy (HAART) or those with active hepatitis A, B, or C infection

• Patients meeting criteria for symptomatic multiple myeloma by one of thefollowing:(a) Lytic lesions on imaging (b) Plasmacytoma, (c) Hypercalcemia withoutany alternate etiology, or (c) Bone marrow plasma cell infiltrate of greater than 60%