Daratumumab, Bortezomib, Dexamethasone, Pegylated Liposomal Doxorubicin Hydrochloride, and Lenalidomide in Treating Participants With Plasma Cell Leukemia

• Documented informed consent of the participant and/or legally authorized representative. Assent, when appropriate, will be obtained per institutional guidelines.
• Willingness to provide bone marrow and peripheral blood samples for research purposes. If unavailable, exceptions may be granted with study principal investigator (PI) approval.
• All study participants must be registered into the mandatory Revlimid Risk Evaluation and Mitigation Strategies (REMS) program and be willing to comply with its requirements.
• Karnofsky performance status (KPS) > 60.
• Plasma cell leukemia; either newly diagnosed or relapsed: defined as the presence of > 2 x 10\^9/L peripheral blood plasma cells or plasmacytosis accounting for > 20% of the differential white cell count.

• Within 14 days prior to day 1 of protocol therapy unless otherwise stated: Absolute neutrophil count (ANC) >= 500/mm\^3

  • NOTE: Growth factor is not permitted within 14 days of ANC assessment unless cytopenia is secondary ot disease involvement.
• Within 14 days prior to day 1 of protocol therapy unless otherwise stated: Total bilirubin =\< 2.0 x ULN (unless has Gilbert's disease).
• Within 14 days prior to day 1 of protocol therapy unless otherwise stated: Aspartate aminotransferase (AST) =\< 3.0 x ULN.
• Within 14 days prior to day 1 of protocol therapy unless otherwise stated: Alanine aminotransferase (ALT) =\< 3.0 x ULN.
• Within 14 days prior to day 1 of protocol therapy unless otherwise stated: Creatinine clearance of >= 30 mL/min per 24 hour urine test or the Cockcroft-Gault formula.
• Within 14 days prior to day 1 of protocol therapy unless otherwise stated: Left ventricular ejection fraction (LVEF) > 45%

• Within 14 days prior to day 1 of protocol therapy unless otherwise stated: Hemoglobin >= 8.0 g/dL

  • Note: Transfusion support is allowed.

• Within 14 days prior to day 1 of protocol therapy unless otherwise stated: Seronegative for human immunodeficiency virus (HIV) antigen-antibody (Ag/Ab) combo, hepatitis C virus (HCV), active hepatitis B virus (HBV) (surface antigen negative), and syphilis (RPR).

  • If positive, hepatitis C RNA quantitation must be performed.

• Within 14 days prior to day 1 of protocol therapy unless otherwise stated: Meets other institutional and federal requirements for infectious disease titer requirements.

  • Note: Infectious disease testing to be performed within 28 days prior to day 1 of protocol therapy.
• Within 14 days prior to day 1 of protocol therapy unless otherwise stated: Women of childbearing potential (WOCBP): negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.

• Agreement by females and males of childbearing potential* to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 6 months after the last dose of protocol therapy.

  • Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only).
• Women of childbearing potential must follow pregnancy testing requirements as outline in REMS program material.

Exclusion Criteria:

• Progression or intolerance to daratumumab, bortezomib, or lenalidomide.
• Prior stem cell transplant.

• Participant is receiving concurrent chemotherapy or biologic or hormonal therapy for cancer treatment.

  • Note: Concurrent use of hormones for noncancer-related conditions (e.g., insulin for diabetes) is acceptable.
• Vaccination with live attenuated vaccines within 4 weeks of first study agent administration.

• Participant is currently using or has used immunosuppressive medication within 14 days prior to the first study dose of study treatment. The following are exceptions:

  • Intranasal, topical, inhaled, or local steroid injections (e.g., intra-articular injection)
  • Chronic systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or equivalent
  • Steroids as premedication for hypersensitivity reactions (e.g., infusion-related reactions, computed tomography [CT] scan premedication).
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent.
• Has known chronic obstructive pulmonary disease with a forced expiratory volume in 1 second (FEV1) \< 50% of predicted normal.
• Has known moderate or severe persistent asthma within the past 2 years, or currently has uncontrolled asthma of any classification.
• Clinically significant uncontrolled illness.
• Active infection requiring intravenous antibiotics or antifungals within 14 days prior to start of study treatment.
• Known history of immunodeficiency virus (HIV) or hepatitis B or hepatitis C infection.
• Grade >= 3 peripheral neuropathy, or grade >= 2 with pain on clinical examination during the screening period.
• Evidence of current uncontrolled cardiovascular conditions, including cardiac arrhythmias, congestive heart failure, angina, or myocardial infarction within the past 6 months. Note: Prior to study entry, any electrocardiogram (ECG) abnormality at screening must be documented by the investigator as not medically relevant.
• Other active malignancy. Exceptions: Non-melanoma skin cancer, ductal breast carcinoma in situ (DCIS) or carcinoma-in-situ of the cervix. Note: If there is a history or prior malignancy, they must not be receiving other specific treatment for their cancer. Prior malignancy treated with curative intent is not an exclusion.
• Females only: Pregnant or breastfeeding.
• Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures.
• Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics).