Daratumumab Maintenance Therapy for Improving Survival in Patients with Light Chain Amyloidosis, EMILIA Trial

Eligibility Criteria

• * Age \>= 18 years
• * Histological confirmation of AL amyloidosis with adequate typing (mass spectrometry, immunohistochemistry, immunofluorescence, immunogold)
• * AL amyloidosis with organ disease requiring therapy
• * NOTE: Disease requiring therapy is referred to the time of diagnosis. There are no limitations in baseline measurable disease parameters
• * Patients must have monoclonal protein studies (serum free light chain assay, serum immunofixation or serum MASS-FIX) obtained at time of diagnosis before induction therapy initiated and available for review to be enrolled.
• * NOTE: Patients are allowed to participate in this study if urine electrophoresis immunofixation study was not done at time of diagnosis or cannot be obtained
• * Patients must have completed 6 cycles of daratumumab (Dara)-CyBorD-based induction treatment =\< 84 days prior to registration
• * Patients must have achieved a hematological complete response (CR) (irrespective of organ response achievement) or hematological very good partial response (VGPR) (irrespective of organ response achievement) or hematological low-difference in involved and uninvolved free light chain (dFLC) partial response (PR) (irrespective of organ response achievement) or hematological PR with at least one organ response after receiving Dara-CyBorD-based induction.
• * NOTE: Patients with baseline dFLC \< 5 mg/dL, must have achieved hematological CR, or dFLC \< 1 mg/dL or achieved organ response prior to randomization
• * Patients in whom bortezomib and/or cyclophosphamide were omitted from induction due to toxicity concerns or adverse effects are allowed. Patients must receive at least daratumumab and dexamethasone at induction to qualify for the study
• * NOTE: Dexamethasone use does not need to be carried to end of induction for eligibility consideration
• * Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, 2 or 3
• * Hemoglobin \>= 8.0 g/dL (obtained =\< 28 days prior to registration)
• * Absolute neutrophil count (ANC) \>= 1000/mm\^3 (obtained =\< 28 days prior to registration)
• * Platelet count \>= 50,000/mm\^3 (obtained =\< 28 days prior to registration)
• * Negative pregnancy test done =\< 7 days prior to registration, for persons of childbearing potential only.
• * NOTE: If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
• * Provide written informed consent
• * NOTE: Informed consent required =\< 90 days prior registration
• * Ability to complete questionnaire(s) by themselves or with assistance
• * Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)
• * Any of the following because this study involves an agent that has possible genotoxic, mutagenic and teratogenic effects:
• * Pregnant persons
• * Nursing persons
• * Persons of childbearing potential (and persons able to father a child) who are unwilling to employ adequate contraception
• * Received \>1 cycle of daratumumab maintenance after end of induction therapy and prior to registration
• * Multiple myeloma at time of diagnosis as defined by any of the following:
• * Hypercalcemia: Serum calcium \> 1 mg/dL higher than upper limit of normal or \> 11 mg/dL
• * Renal insufficiency: Creatinine clearance \< 40 mL per min or serum creatinine \> 2 mg/dL attributed to high circulating light chains (i.e. cast nephropathy) or hypercalcemia
• * Anemia: Hemoglobin \> 2 g/dL below lower limit of normal, or \< 10 g/dL, attributed to high marrow myeloma infiltration
• * Bone lesions: \>= 1 osteolytic lesion on skeletal x-ray, computed tomography (CT), or positron emission tomography (PET)-CT (bone imaging is not mandatory but based on clinical suspicion)
• * Clonal bone marrow plasma cells \>= 60%
• * \> 1 focal lesion on magnetic resonance imaging (MRI) (MRI is not mandatory but based on clinical suspicion)
• * If bone imaging (CT, MRI, PET-CT) was not done at time of diagnosis it is not needed to be performed at registration to rule out bone disease
• * \>= 40% BMPCs irrespective of the above
• * The study will allow patients with involved: uninvolved serum-free light chain (sFLC) ratio \>= 100 if this is the only criteria that defines amyloidosis if all the above criteria are not met
• * Seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen \[HBsAg\]). Note: Subjects with resolved infection (i.e., subjects who are HBsAg negative but positive for antibodies to hepatitis B core antigen \[anti-HBc\] and/or antibodies to hepatitis B surface antigen \[anti-HBs\]) must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) deoxyribonucleic acid (DNA) levels. Those who are PCR positive will be excluded. EXCEPTION: Subjects with serologic findings suggestive of HBV vaccination (anti-HBs positivity as the only serologic marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV DNA by PCR
• * Immunocompromised patients and patients known to be human immunodeficiency virus (HIV) positive and currently receiving antiretroviral therapy.
• * NOTE: Patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for this trial
• * Uncontrolled intercurrent illness including, but not limited to:
• * Ongoing or active infection
• * Unstable angina pectoris
• * Psychiatric illness/social situations that would limit compliance with study requirements