Cyclophosphamide, Bortezomib, and Dexamethasone in Treating Patients With Newly Diagnosed Multiple Myeloma

DISEASE CHARACTERISTICS:

• Confirmed diagnosis of symptomatic multiple myeloma
• Durie Salmon stage 2 or higher
• Previously untreated multiple myeloma (including immunomodulatory drugs such as thalidomide) with the exception of bisphosphonates
• Evaluable or measurable disease, as defined by at least one of the following:
• Serum monoclonal protein ≥ 1 g/dL (measurable disease)
• Urine monoclonal protein ≥ 200 mg/24 hours by protein electrophoresis (measurable disease)
• Serum-free light chains (FLC) ≥ 10 mg/dL, kappa or lambda, accompanied by an abnormal kappa/lambda ratio

Serum FLC's should only be used for patients without measurable serum or urine m-spike

• Monoclonal bone marrow plasmacytosis ≥ 30% (evaluable disease)
• Patients diagnosed with smoldering myeloma or monoclonal gammopathy of undetermined significance are not eligible

PATIENT CHARACTERISTICS:

Inclusion criteria

• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0, 1, or 2
• ECOG PS of 3 will be allowed if secondary to pain in the opinion of the Investigator
• Total bilirubin normal OR direct bilirubin ≤ 2.0 mg/dL
• Alkaline phosphatase ≤ 3 times upper limit of normal (ULN)
• AST ≤ 3 times ULN
• Creatinine ≤ 3.5 mg/dL
• Absolute neutrophil count ≥ 1, 000/mm³ without transfusion or growth factor
• Platelet count ≥ 100, 000/mm³ without transfusion or growth factor
• Willingness and the physical and mental capability to provide written informed consent
• Willingness to return to Mayo Clinic Arizona/Princess Margaret Hospital for follow-up
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

Exclusion criteria

• Peripheral sensory neuropathy ≥ grade 2 as defined by National Cancer Institute (NCI) Common Terminology for Common Adverse Events (CTCAE) version 3.0
• Known hypersensitivity to compounds containing boron or mannitol
• Active uncontrolled infection
• Severe cardiac comorbidity including but not limited to:
• New York Heart Association class III or IV heart failure
• History of myocardial infarction within the past 6 months
• Uncontrolled angina or electrocardiographic (ECG) evidence of acute ischemia
• Severe uncontrolled ventricular arrhythmias or ECG evidence of active conduction system abnormalities
• Cardiac amyloidosis with hypotension (i.e., systolic blood pressure < 100 mm Hg)
• Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent study compliance or completion of study treatment

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Prior high-dose corticosteroid therapy for 12 days or less is permitted for emergent complications from newly diagnosed multiple myeloma
• More than 14 days since prior investigational agents
• No concurrent steroids or any other anticancer agents or treatments
• Patients may receive the equivalent of up to 20 mg prednisone per day for concurrent illness or adrenal replacement therapy
• Concurrent palliative radiotherapy for bony pain or fracture is allowed