DISEASE CHARACTERISTICS:

• Multiple myeloma of any stage confirmed by:

  • Bone marrow plasmacytosis with at least 10% plasma cells, sheets of plasma cells, or biopsy proven plasmacytosis
  • Myeloma (M) protein in serum and/or urine

• Measurable disease by at least one of the following:

  • Serum M-component at least 1.0 g/dL by electrophoresis

    • Baseline measurement by nephelometry also, if used to follow response
  • Urine M-protein excretion greater than 200 mg/24 hours by electrophoresis

• The following are not considered measurable but are followed for response:

  • Lytic bone lesions
  • Bone marrow plasmacytosis
  • Anemia
  • Serum beta 2-microglobulin

• Objective evidence of progression by at least one of the following:

  • Increased serum M-protein (by electrophoresis unless M-spike less than 1.5 g/dL)

    • At least 50% above lowest remission level or by at least 2 g/dL
    • To more than 1.0 g/dL if sole protein indication of relapse
    • Nephelometry may be used instead of electrophoresis

  • Increased urine M-protein

    • To 50% above lowest level OR by 2 g/24 hours
    • To greater than 200 mg/24 hours
  • Definite new lytic bone lesions or at least a 50% increase in size of existing lesions (discussion with ECOG Study Chairman required if sole indication of progression)

  • Increase in serum or urine M-protein by 25% to under 50% (as above) plus one of the following:

    • Serum calcium greater than 12 mg/dL without other cause

    • Hemoglobin decreased by more than 2.0 g/dL not attributed to chemotherapy, interferon therapy, or a myelodysplastic syndrome

      • Less than 11 g/dL in men
      • Less than 10 g/dL in women
    • At least a 50% increase in bone marrow plasmacytosis

• Failure of prior cytotoxic therapy defined by one of the following:

  • Never responded
  • Relapsed within 2 months of last treatment
  • Relapsed 2-12 months after last treatment following initial response

• Adequate prior chemotherapy required, e.g.:

  • At least 2 courses of combination chemotherapy (e.g., VBMCP, VBAP, MP)

    • Prior vincristine, doxorubicin, and dexamethasone (VAD) allowed

      • No demonstrated resistance to VAD
      • At least 3 months since prior VAD
    • Cumulative doxorubicin dose no more than 250 mg/m2

    • Prior autologous peripheral blood stem cell transplant allowed if performed prior to development of drug resistance

      • No prior allogeneic transplant
• No smoldering myeloma, localized plasmacytoma, or monoclonal gammopathy of undetermined significance (MGUS)

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-3

Life expectancy:

• At least 2 months

Hematopoietic:

• Absolute neutrophil count at least 1,000/mm^3
• Platelet count at least 50,000/mm^3

Hepatic:

• Bilirubin less than 1.5 times upper limit of normal (ULN)
• AST less than 1.5 times ULN
• No chronic or active hepatitis or cirrhosis

Renal:

• Creatinine less than 3.0 mg/dL

Cardiovascular:

• Ejection fraction at least 50%
• No history of congestive heart failure
• No overt angina despite medication
• No myocardial infarction within 2 months
• No poorly controlled hypertension (i.e., pressure 200/110 or higher despite medication)

• No arrhythmia requiring therapy (i.e., sustained atrial or ventricular arrhythmia or multifocal premature ventricular contraction)

  • Digoxin to control ventricular rate of atrial fibrillation that has been chronic for more than 1 month allowed

Neurologic:

• No peripheral neuropathy with weakness
• No cerebellar disease with ataxia

Gastrointestinal:

• Adequate gastrointestinal function to allow absorption of PSC 833
• No active peptic ulcer

Other:

• No hypersensitivity to PSC 833 or cyclosporine
• No active infection
• HIV negative
• No uncontrolled diabetes mellitus
• No second malignancy within the past 5 years except curatively treated nonmelanomatous skin cancer, carcinoma in situ of the cervix, or other localized cancer treated with surgery alone
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No other serious medical problem unless sufficiently stabilized

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Prior biologic therapy (e.g., interferon) allowed

Chemotherapy:

• See Disease Characteristics
• At least 3 weeks since other prior chemotherapy (including plicamycin)

Endocrine therapy:

• At least 2 weeks since high dose steroids (at least 100 mg/m2/day of prednisone or at least 40 mg/day of dexamethasone (including steroids for hypercalcemia)

Radiotherapy:

• At least 2 weeks since prior radiotherapy except limited radiotherapy to a single bone lesion

Surgery:

• At least 4 weeks since prior major surgery

Other:

• No concurrent anticoagulants
• No concurrent drugs known to modulate cyclosporine blood concentrations