Dexamethasone and Chemotherapy With or Without Plasma Exchange in Patients With Newly Diagnosed Multiple Myeloma and Acute Kidney Failure

OBJECTIVES:

Primary

• Compare the effect of dexamethasone and cytotoxic chemotherapy with vs without plasma exchange on the likelihood of renal recovery (i.e., dialysis-independent at 100 days) in patients with newly diagnosed multiple myeloma and acute renal failure.

Secondary

• Compare the overall survival of patients treated with these regimens.
• Compare the quality of life of patients treated with these regimens.
• Determine the value of renal histology in predicting recovery of renal function in these patients.
• Determine the value of serum free light chain assay in determining disease response and renal function recovery in these patients.

OUTLINE: This is a randomized, controlled, open-label, multicenter study. Patients are stratified according to planned chemotherapy (vincristine and doxorubicin hydrochloride (VA) or VA-like chemotherapy vs thalidomide-containing chemotherapy vs alkylating agent vs other), frequency of chemotherapy courses (1-3 weekly vs 4 weekly), need for dialysis at randomization (yes vs no), and age (< 65 years vs ≥ 65 years). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral dexamethasone, at least twice daily, on days 1-4 and 9-12. Patients undergo plasma exchange by cytocentrifugation or plasmafiltration over 2-3 hours in weeks 1 and 2 (7 treatments total; 4 of them in week 1). Patients then receive planned chemotherapy per local clinician on days 17-100. Chemotherapy may continue after 100 days at the discretion of the local clinician.
• Arm II: Patients receive dexamethasone and planned chemotherapy as in arm I. Quality of life is assessed at baseline, day 100, and 6 and 12 months.

After completion of study treatment, patients are followed at 6 and 12 months and then annually thereafter.

Peer Reviewed and Funded or Endorsed by Cancer Research UK

PROJECTED ACCRUAL: A total of 280 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Newly diagnosed multiple myeloma (MM), meeting ≥ 2 of the following criteria:

• Serum or urine* paraprotein
• Bone marrow showing > 10% plasma cells
• Lytic bone lesions NOTE: *The presence of typical myeloma kidney on renal biopsy is considered equivalent to the demonstration of urine paraprotein by electrophoresis
• Acute renal failure attributable to MM, meeting both of the following criteria:

• Creatinine > 5.65 mg/dL OR urine output < 400 mL/day OR requires dialysis
• Unresponsive to treatment with fluids and/or treatment of hypercalcemia with bisphosphonates
• No significant intrinsic renal disease unrelated to MM

PATIENT CHARACTERISTICS:

• Platelet count ≥ 50,000/mm³
• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• ALT and AST ≤ 2.5 times ULN
• No contraindications to study medication, including the following:

• Active or recent peptic ulcer
• Known significant cardiac insufficiency
• Allergy to study medications
• Not pregnant or nursing
• Fertile patients must use effective contraception
• No known HIV positivity

PRIOR CONCURRENT THERAPY:

• No prior chemotherapy for MM
• Prior steroid therapy of ≤ 3 days duration for MM allowed