Pomalidomide and Dexamethasone (PDex) in AL Amyloidosis

Inclusion Criteria:

* At least 18 years.
* Diagnosis of systemic AL amyloidosis.
* Symptomatic organ (heart, kidney, liver, peripheral nervous system, or soft tissue) involvement.
* Patients achieving less than complete response after initial treatment with an alkylating agent (melphalan or cyclophosphamide) and bortezomib. Patients with AL amyloidosis who received 1 previous treatment, but who could not be treated with alkylators and/or bortezomib due to contraindications, will be eligible.
* Measurable disease: difference between amyloidogenic (involved) and uninvolved free light chains (dFLC) \> 50 mg/L.
* Hb ≥ 10 g/dL
* ANC ≥ 1500/uL.
* Platelet count ≥ 100000/uL.
* eGFR ≥ 30 mL/min per 1.73 m2.
* Performance status (ECOG) \< 3.
* Total bilirubin \< 2.5 mg/dL.
* Alkaline phosphatase \< 5 × url.
* ALT \< 3 × url.
* Female: FCBP must have two negative pregnancy tests (sensitivity of at least 50 mIU/mL) prior to starting study drug. The first pregnancy test must be performed within 10-14 days prior to the start of study drug and the second pregnancy test must be performed within 24 hours prior to the start of study drug. The subject may not receive study drug until the Investigator has verified that the results of these pregnancy tests are negative. Will be warned that sharing study drug is prohibited and will be counseled about pregnancy precautions and potential risks of fetal exposure. Must agree to abstain from donating blood during study participation and for at least 28 days after discontinuation from the study.
* Male: Must agree to use a latex condom during sexual contact with females of childbearing potential while participating in the study and for at least 28 days following discontinuation from the study even if he has undergone a successful vasectomy. Will be warned that sharing study drug is prohibited and will be counseled about pregnancy precautions and potential risks of fetal exposure. Must agree to abstain from donating blood, semen, or sperm during study participation and for at least 28 days after discontinuation from the study.

During study participation and for 28 days following discontinuation from the study:

* All subjects: No more than a 28-day supply of study drug will be dispensed at a time.
* Female: FCBP with regular cycles must agree to have pregnancy tests weekly for the first 28 days of study participation and then every 28 days while on study, at study discontinuation, and at day 28 following discontinuation from the study. If menstrual cycles are irregular, the pregnancy testing must occur weekly for the first 28 days and then every 14 days while on study, at study discontinuation, and at days 14 and 28 following discontinuation from the study. In addition to the required pregnancy testing, the Investigator must confirm with FCBP that she is continuing to use two reliable methods of birth control at each visit. Counseling about pregnancy precautions and the potential risks of fetal exposure must be conducted at a minimum of every 28 days. During counseling, subjects must be reminded to not share study drug and to not donate blood. Pregnancy testing and counseling must be performed if a subject misses her period or if her pregnancy test or her menstrual bleeding is abnormal. Study drug treatment must be discontinued during this evaluation. Females must agree to abstain from breastfeeding during study participation and for at least 28 days after discontinuation from the study.
* Male: Counseling about the requirement for latex condom use during sexual contact with females of childbearing potential and the potential risks of fetal exposure must be conducted at a minimum of every 28 days. During counseling, subjects must be reminded to not share study drug and to not donate blood, sperm, or semen.

Exclusion Criteria:

* Amyloid-specific syndrome, such as carpal tunnel syndrome or skin purpura as the only evidence of disease.
* New York Heart association (NYHA) class IV.
* Known positivity for HIV or active hepatitis infection.
* Pregnant or nursing women (men must agree to use an acceptable method for contraception for the duration of the study).
* Uncontrolled infections.
* Other active malignancies.
* Patient has a prior history of thrombosis or venous thromboembolism or pulmonary embolism.
* Known hypersensitivity to thalidomide or lenalidomide including development of erythema.
* Previous or ongoing psychiatric illness (with the exclusion of reactive depression).