Rituximab in Treating Patients With Peripheral Neuropathy Caused by Monoclonal Gammopathy of Undetermined Significance

DISEASE CHARACTERISTICS:

• Diagnosis of monoclonal gammopathy of undetermined significance (MGUS), as evidenced by 1 of the following criteria:

  • Documented monoclonal protein in the serum (< 3 g/dL) or urine
  • Monoclonal serum free light chain, with at least 50% of patients having an IgM paraprotein (the balance being IgG or IgA subtypes)
• Neuropathy Impairment Score (NIS) ≥ 25
• Stable or progressive neuropathy (i.e., not currently improving), as judged by NIS values that have not fallen ≥ 10 (between enrollment and the last documented value), at least 1 month but not greater than 3 months prior to enrollment
• No evidence of amyloidosis or overt lymphoma, overt myeloma, or Waldenström macroglobulinemia with end organ damage
• No evidence of multiple myeloma, AL-amyloidosis
• No evidence of POEMS, diabetes mellitus, alcohol induced neuropathy, untreated hypothyroidism, vitamin B12 deficiency, Sjögren syndrome, and other causes of neuropathy

PATIENT CHARACTERISTICS:

Inclusion Criteria:

• Not pregnant
• Negative serum pregnancy test

• Fertile patients must use an acceptable method of birth control during treatment and for 6 months after completion of treatment

  • One of the following birth control measures must be used: birth control pills, intrauterine device, contraceptive injections (Depo-Provera), barrier methods such diaphragm, condom or contraceptive sponge with spermicide
• Adequate bone marrow function as indicated by sufficient precursors of all three cell lines and cellularity of at least 20% on bone marrow biopsy within 6 months
• Platelets > 100,000/mm³
• ANC > 1,000/mm³
• Hemoglobin > 7 g/dL
• Serum creatinine < 3.0 mg/dL
• AST or ALT < 2 times upper limit of normal

• No history of psychiatric disorder requiring hospitalization, psychiatric consultation, or psychotropic medications within the last year

  • Patients with controlled depression are eligible, as defined by the following:

    • Stable for at least 6 months
    • No increase in psychotropic medications

Exclusion criteria:

• History of HIV infection or seropositivity

• History or serological profile suggesting prior hepatitis B virus (HBV) infection (i.e., HbsAg or anti-HBs with anti-HBc)

  • Prior HBV vaccination with isolated anti-HBs antibodies is not an exclusion criterion
• HBV infection or non-vaccination-related HBV seropositivity
• Active infection
• New York Heart Association class III or IV heart disease
• History or baseline ECG tracing demonstrating severe recurrent or severe recent (within 3 months) cardiac dysrhythmia (e.g., ventricular tachycardia, torsades de pointes, or other serious ventricular dysrhythmias) requiring implanted defibrillator treatment

• Confirmed diagnosis of systemic lupus erythematosus (SLE)

  • An isolated low titer positive antinuclear antibody test without clinical evidence of SLE is not an exclusion criterion
• Concomitant malignancies or previous malignancies within the last five years, with the exception of adequately treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix
• Malignancy associated with a paraneoplastic neuropathy
• A history of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies
• A history of known severe primary or secondary immunodeficiency (e.g., common variable immunodeficiency)
• Significant other uncontrolled medical illnesses that may interfere with drug delivery or interpretation of results

PRIOR CONCURRENT THERAPY:

• No live vaccine therapy within 30 days of enrollment
• No plasmapheresis within 3 months
• No high-dose intravenous immunoglobulin, chemotherapeutic agents, or high-dose corticosteroids (> 10 mg daily or every other day) within 3 months
• No systemic corticosteroids within 3 months (unless needed for adrenal insufficiency or at a stable dose ≤ 10 mg daily)
• No high-dose (> 250 mg/day) vitamin B6 within the past month
• No prior treatment with thalidomide or neurotoxic drugs (e.g., vinca alkaloids, taxol, or platinum)