The value of ifosfamide in the treatment of multiple myeloma

Primary high-dose therapy with autologous peripheral blood progenitor cell (PBPC) reinfusion for advanced multiple myeloma (MM) appears superior to classic conventional chemotherapy with alkylators and corticosteroids. Long- term conventional therapy with the standard alkylating agent melphalan critically reduces the PBPC pool. Moreover, cases of highly proliferative MM respond less readily to melphalan than to a combination of other alkylating agents. Oxazaphosphorines like ifosfamide (IFO), either as single agent or in combination with other drugs show satisfactory response rates without jeopardising the PBPC reserve. IFO-containing combinations as primary induction treatment show reliable PBPC mobilising potency (median 6.1x10⁶ CD34 positive PBPC in a median of 2.5 leucaphereses) leucocytes. Combination with epirubicin and dexamethasone leads to response rates equivalent to infusional protocols (67.2% CR and PR according to MRC criteria; median paraprotein reduction to 27% of the initial value) even in melphalan- pretreated patients. The tubulotoxic effect of IFO in patients with compromised renal function is rare and reversible, allowing the use of this agent in 66 out of 69 patients eligible for autologous transplant in our series. Apart from this, IFO at doses up to and beyond 6 g/m² appears to be an effective and nontoxic component of induction PBPC mobilising treatment in MM.