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

Inclusion 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)

Exclusion Criteria:

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