RATIONALE: Bortezomib may stop the growth of cancer by blocking the enzymes necessary for tumor cell growth.

PURPOSE: Phase II trial to study the effectiveness of bortezomib in treating patients who have untreated or relapsed Waldenstrom's macroglobulinemia.

OBJECTIVES:

• Determine the efficacy of bortezomib, in terms of response rate, in patients with previously untreated or relapsed Waldenstrom's macroglobulinemia.
• Determine the toxicity of this drug in these patients.
• Determine the time to progression, stable disease duration, and response duration in patients treated with this drug.

OUTLINE: This is a multicenter study.

Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients are followed at 4 weeks. Patients with complete or partial response or stable disease are followed every 3 months thereafter.

PROJECTED ACCRUAL: A total of 15-25 patients will be accrued for this study within 1.5-2 years.

DISEASE CHARACTERISTICS:

• Diagnosis of Waldenstrom's macroglobulinemia confirmed by immunofixation or immunoelectrophoresis

  • Newly diagnosed or untreated with IgM ≥ 20 g/L OR
  • Previously treated with IgM ≥ 5 g/L

• Non-refractory, defined as no disease progression during prior therapy or within 4 weeks of the last dose of most recent prior therapy (12 weeks for rituximab)

• Must have 1 or more of the following:

  • Symptomatic lymphadenopathy
  • Hepatomegaly and/or splenomegaly
  • Anemia (i.e., hemoglobin < 11.0 g/dL)
  • Hyperviscosity syndrome

• No other lymphoproliferative disease including transformed aggressive lymphoma

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• At least 12 weeks

Hematopoietic

• See Disease Characteristics
• Absolute granulocyte count ≥ 1,000/mm^3
• Platelet count ≥ 50,000/mm^3

Hepatic

• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST or ALT ≤ 2.5 times ULN

Renal

• Creatinine ≤ 1.5 times ULN

Other

• No uncontrolled bacterial, fungal, or viral infection
• No pre-existing sensory or motor neurotoxicity grade 2 or greater
• No other prior malignancy except adequately treated nonmelanoma skin cancer, curatively treated carcinoma in situ of the cervix, or other curatively treated solid tumor for which patient has been disease free for at least 5 years
• No other serious illness or medical condition that would preclude study participation
• No unreasonable geographical limitations
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Chemotherapy
• See Disease Characteristics
• At least 12 weeks since prior rituximab (for patients who have progressed)
• At least 24 weeks since prior rituximab (for patients who have not progressed)
• No prior high-dose chemotherapy and stem cell transplantation
• No prior radioactive monoclonal antibodies

Chemotherapy

• See Disease Characteristics

• See Biologic therapy

• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)

• No more than 2 prior chemotherapy regimens

  • The same chemotherapy combination given for first-line and second-line therapy is considered 2 regimens
  • Single-agent rituximab not considered 1 prior regimen

• No concurrent cytotoxic chemotherapy

Endocrine therapy

• No concurrent corticosteroids

Radiotherapy

• At least 4 weeks since prior radiotherapy (except for low-dose, non- myelosuppressive radiotherapy) and recovered
• No prior radiotherapy to more than 25% of bone marrow

Surgery

• At least 4 weeks since prior major surgery

Other

• At least 4 weeks since prior plasmapheresis
• At least 4 weeks since prior investigational anticancer therapy
• No other concurrent investigational anticancer agents or therapies