Intravenous melphalan and dexamethasone followed by lymphoblastoid alpha interferon in higher risk multiple myeloma patients

Intermittent courses of melphalan and prednisone is still the standard chem otherapy for the initial treatment of multiple myeloma (MM) in patients who cannot undergo high-dose chemotherapy/radiotherapy with either allogeneic or autologous stem cell transplantation. However, the absorption of the dru g from the gastrointestinal tract is highly variable from patient to patien t and therefore, different plasma levels of the drug are reached in the blo od of individual MM patients. In order to overcome this limitation we decid ed to use intermediate dose (15-30 mg/m(2), day 1) intravenous melphalan in resistant or relapsing MM patients as well as in untreated patients not el igible for a more aggressive protocol. Moreover, considering the good resul ts obtained by other investigators using dexamethasone alone or associated with interferon in the treatment of resistant or relapsing MM patients, dex amethasone (40 mg total dose, day 1) and the lymphoblastoid alpha interfero n (3 MU, 3 times a week x 3 weeks, from day 8 to day 26 of each course) wer e added to intravenous melphalan. Courses were repeated every 5 weeks for a total of 6 cycles. We treated 62 MM patients obtaining a response (defined as reduction > 25% of the initial monoclonal component Value associated wi th disappearance of the clinical symptoms) in 38 out 62 evaluable patients (61%) and stable disease (defined as a decrease of < 25% in the base-line s erum monoclonal component level with disappearance of all symptoms present at diagnosis) in 9 (14.5%) more patients. The overall median response durat ion was 14 months and the overall median survival duration (from the time o f inclusion in this protocol) for the 62 patients entered into the study wa s 34 months. No severe (Grade 3-4 of the WHO) hematological as well as non hematological toxicities were observed. This lack of severe toxicity allowe d us to administer the drugs on an outpatient basis. In conclusion, the ove rall response and the low grade of toxicity in this category of patients ar e encouraging and suggest that this protocol is both effective and safe tre atment for high risk MM patients.