Melphalan and Dexamethasone With or Without Bortezomib in Treating Patients With Previously Untreated Systemic Light-Chain Amyloidosis

Inclusion Criteria:

* Histologically confirmed diagnosis of systemic light-chain amyloidosis

  * Histologic diagnosis of disease must be confirmed by pathology (positive Congo red stain with green birefringence on polarized light microscopy)
  * Genetic testing must be negative for transthyretin mutations associated with hereditary amyloidosis (required in patients who are African-American or who present with peripheral neuropathy as the dominant organ involvement)
* Measurable disease, defined by \>= 1 of the following:

  * Serum M-protein \>= 1 g/dL by serum protein electrophoresis (SPEP)
  * Difference between involved and uninvolved free light chain be \>4.0mg/dL provided the kappa to lambda free light chain (FLC) ratio is abnormal
* Symptomatic organ involvement\* (heart, kidney, liver/gastrointestinal tract, peripheral nervous system, or soft tissue), defined as any of the following:

  * NOTE: \*Carpal tunnel syndrome skin purpura or the presence of vascular amyloid on a bone marrow biopsy alone are not sufficient to meet criteria for "symptomatic organ involvement"
  * Renal involvement is defined as proteinuria (predominantly albumin) \> 0.5 g/day by 24-hour urine collection
  * Cardiac involvement is defined as the presence of a mean left ventricular wall thickness of \> 12 mm by echocardiogram in the absence of a history of hypertension or valvular heart disease or in the presence of unexplained low voltage (\< 0.5 mV) by electrocardiogram
  * Hepatic involvement is defined as hepatomegaly or an alkaline phosphatase \> 1.5 times upper limit of normal (ULN)
  * Peripheral nerve involvement is defined by clinical history or abnormal sensory and/or motor findings on neurologic exam
  * Gastrointestinal (GI) involvement is defined as gross GI bleeding or diarrhea (at least 4 stools per day over baseline); a positive GI biopsy is not sufficient to document clinical involvement
  * Autonomic nerve involvement is defined as orthostasis, symptoms of nausea or dysgeusia, gastric atony by gastric emptying scan, diarrhea, or constipation
  * Soft tissue and lymphatic involvement may be ascertained based on classic physical exam findings (macroglossia, shoulder pad sign, raccoon eyes, carpal tunnel syndrome, synovial enlargement, firm enlarged lymph nodes) or biopsy
* Ineligible for autologous stem cell transplantation with melphalan 200 mg/m\^2 or refuses to undergo transplantation
* Eastern Cooperative Oncology Group (ECOG) performance status 0-2
* Amyloid cardiac biomarker stage I or II disease

  * The amyloid cardiac staging system is based on NT-proBNP and troponin-T levels. If troponin T (cTnT) is not available at local institution then troponin I (cTnI) may be used. Thresholds for cTnT, cTnI, and NT-proBNP are \< 0.035 ug/L, \< 0.1 ug/L, and \< 332 ng/L, respectively. Stage I patients have both troponin-T (or I) and NT-proBNP below the threshold. Stage II patients have either troponin-T (I) or NT-proBNP above the threshold. Stage III patients have troponin-T (or I) and simultaneous NT-proBNP above the threshold. Stage III patients are further classified as "better risk" if NT-proBNP is over 332 ng/L but less than 6000 ng/L
* Negative pregnancy test
* Fertile patients must use effective contraception
* The absence of supine systolic blood pressure \< 100 mmHg and difficult to manage symptomatic orthostatic hypotension
* Absolute neutrophil count (ANC) \> 1,500/mm\^3
* Platelet count \> 140,000/mm\^3
* Hemoglobin \> 10 g/dL
* Total bilirubin \< 2.5 mg/dL
* Alkaline phosphatase \< 5 times upper limit of normal (ULN)
* Aspartate aminotransferase (AST) \< 3 times ULN
* Creatinine clearance \> 30 mL/min
* Bone marrow plasma cells \< 30%
* Human immunodeficiency virus (HIV)-positivity allowed provided the following criteria are met:

  * No history of acquired immunodeficiency syndrome (AIDS)-defining events including history of CD4 cell count \< 200/mm\^3
  * Current CD4 cell count \>= 350/mm\^3
  * Not receiving zidovudine or stavudine
  * No secondary amyloidosis
* More than 3 weeks since radiotherapy

  * Enrollment of subjects who require radiotherapy (which must be localized in field size) should be deferred until the radiotherapy is completed and 3 weeks have elapsed since the last date of therapy
* More than 14 days since prior and no concurrent participation in clinical trials with other investigational agents not included in this trial

Exclusion Criteria:

* Pregnant or nursing
* Clinically overt myeloma (hypercalcemia or lytic bone lesions)
* Prior chemotherapy or radiotherapy for the treatment of myeloma or systemic light-chain amyloidosis
* History of sustained ventricular tachycardias
* Cardiac syncope
* Uncompensated New York Heart Association (NYHA) class III or IV congestive heart failure
* Uncontrolled infection
* Active malignancy within the past 5 years except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or adequately treated stage I cancer currently in complete remission
* Serious medical or psychiatric illness likely to interfere with study participation, including recent myocardial infarction (within the past 6 months) or poorly controlled diabetes mellitus
* Hypersensitivity to bortezomib, boron, or mannitol
* Grade 2 or higher peripheral neuropathy