Doxorubicin Hydrochloride Liposome, Bortezomib, and Dexamethasone in Treating Patients With Newly Diagnosed Multiple Myeloma

DISEASE CHARACTERISTICS:

• Diagnosis of multiple myeloma based on the following criteria:

  • Major criteria

    • Plasmacytomas on tissue biopsy (1)
    • Bone marrow plasmacytosis (> 30% plasma cells) (2)
    • Monoclonal immunoglobulin spike on serum electrophoresis IgG > 3.5 g/dL or IgA > 2.0 g/dL and kappa or lambda light chain excretion > 1 g/day on 24-hour urine protein electrophoresis (3)

  • Minor criteria

    • Bone marrow plasmacytosis (10% to 30% plasma cells) (a)
    • Monoclonal immunoglobulin present but of lesser magnitude than given under major criteria (b)
    • Lytic bone lesions (c)
    • Normal IgM \< 50 mg/dL, IgA \< 100 mg/dL, or IgG \< 600 mg/dL (d)

• Meets 1 of the following sets of diagnostic criteria:

  • Any two of the major criteria
  • Major criteria 1 and minor criteria b, c, and d
  • Major criteria 3 and minor criteria a or c
  • Minor criteria a, b, c, OR a, b, d

• Measurable disease, defined as a monoclonal immunoglobulin spike on serum electrophoresis ≥ 1 g/dL and/or urine monoclonal immunoglobulin spike ≥ 200 mg/24 hours, or evidence of lytic bone disease

  • No nonmeasurable disease (i.e., non-secretory or oligosecretory multiple myeloma)
• Symptomatic, newly diagnosed, and previously untreated multiple myeloma
• No POEMS syndrome (i.e., plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein [M-protein], and skin changes)
• No plasma cell leukemia

PATIENT CHARACTERISTICS:

• Karnofsky performance status 60-100%
• Life expectancy > 3 months
• ANC ≥ 1,500/mm\^³ (≥ 1,000/mm\^³ if bone marrow is extensively infiltrated)
• Platelet count ≥ 75,000/mm\^³ (≥ 50,000/mm\^³ if bone marrow is extensively infiltrated)
• Hemoglobin ≥ 8.0 g/dL
• AST and ALT ≤ 3.0 times upper limit of normal (ULN)
• Serum bilirubin ≤ 2.0 times ULN
• Creatinine clearance ≥ 30 mL/min OR creatinine > 10 mL/min and \< 30 mL/min for patients with significant myelomatous involvement of the kidneys
• Serum potassium ≥ lower limit of normal (LLN)
• Serum sodium ≥ LLN
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No prior malignancy within the past 5 years except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
• No peripheral neuropathy ≥ grade 2 within past 14 days

• No impaired cardiac function or clinically significant cardiac disease, including any one of the following:

  • Myocardial infarction within the past 6 months
  • New York Heart Association class II-IV heart failure
  • Uncontrolled angina
  • Clinically significant pericardial disease
  • Severe uncontrolled ventricular arrhythmias
  • LVEF below normal by ECHO or MUGA scan

  • ECG evidence of acute ischemia or active conduction system abnormalities

    • Screening ECG abnormality must be documented by the investigator as not medically relevant
• No severe hypercalcemia (i.e., serum calcium ≥ 14 mg/dL [3.5 mmol/L])
• No poorly controlled hypertension, diabetes mellitus, or other serious medical or psychiatric illness that could preclude study treatment

• No known HIV positivity or hepatitis B or C positivity

  • Baseline testing for HIV and hepatitis B or C is not required
• No history of allergic reaction attributable to compounds of similar chemical or biological composition to doxorubicin, bortezomib, boron, or mannitol

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• No prior or concurrent anti-myeloma therapy except steroids

  • Prior prednisone for ≤ 4 days at a total of 400 mg (or an equivalent potency of another steroid) allowed
  • No concurrent corticosteroids (≥ 10 mg prednisone/day or equivalent) other than dexamethasone

• More than 4 weeks since prior major surgery and recovered

  • Prior kyphoplasty with oncotherapeutic drugs allowed at the investigator's discretion
• More than 4 weeks since prior immunotherapy, antibody therapy, or radiotherapy
• More than 14 days since other prior and no other concurrent investigational drugs