Clinical Study of Fludarabine, Mitoxantrone, and Dexamethasone in the Treatment of Refractory or Relapsed Multiple Myeloma.

BACKGROUND & OBJECTIVE: Until today, multiple myeloma is still an incurable malignancy by conventional therapy; it has low complete remission rate and high recurrence rate. Recurrence or relapse of the disease is almost inevitable for most of the patients after several cycles of combined chemotherapy. A safe and effective therapy for the treatment of relapsed and refractory multiple myeloma is urgently needed in clinical practice. This clinical study was designed to compare the safety and efficacy of the fludarabine-based regimen (fludarabine, mitoxantrone and dexamethasone [FMD]) with that of pirarubicin, vincristine and dexamethasone (VAD) in refractory or relapsed multiple myeloma.

METHODS: The clinical data were retrospectively analyzed. The following indices were assessed before, during, and after the treatment in FMD-arm and VAD-arm: the partial remission (PR) rate, overall response (OR) rate, time to achieve PR, the number of patients and time to achieve the following: a decline in the serum M-component of more than 50% of the pre-treatment value, the ratio of myeloma cells in bone marrow drop to less than 50% of the pre-treatment value, the ratio of myeloma cells in bone marrow drop to less than 5% or drop more than 80% than pre-treatment level, the hemoglobin level increased more than 20 g/L, the white blood cell and platelet count of the peripheral blood, serum calcium, creatinine, β₂-microglobin and ALT level, adverse events.

RESULTS: The PR rate and OR rate are significantly higher in the FMD-arm than in the VAD-arm (PR rates were 46.2% vs 22.7% and OR rates were 61.5% vs 31.8%, P <0.05, respectively). The median time to achieve PR was 88 days in the FMD-arm, compared to 68 days in the VAD-arm (P <0.05). Approximately 40.0% of patients in the FMD-arm had >50% decrease in M-component or >20 g/L elevation in hemoglobin, compared to 22.7% and 18.2% in the VAD-arm respectively (P <0.05). The median times to achieve >50% decrease in M-component, decline of >80% of myeloma cells in the bone marrow than the pre-treatment level or ratio drop to less than 5%, or >20g/L elevation in hemoglobin were 62 days, 57 days, and 70 days, respectively. There were no significant differences between groups in serum calcium, creatinine, and ALT level pre-and post-treatment. The level of serum β₂-microglobin was (1042.8±72.3 mg/L) post-treatment in the FMD-arm, which was lower than that observed before treatment (2350.2±184.0 mg/L; P <0.05). Most patients (76.9%) in the FMD-arm occurred III/IV grade leukocytopenia while 81.8% patient were I/II grade in the VAD-arm. The incidences of fever and cough were higher in FMD-arm comparing to VAD-arm (P <0.05). The progression free survival (PFS) on 1st and 2nd year and overall survival (OS) on 2nd year were 46.2%, 30.8% and 53.8% in the FMD-arm, while they were 50%, 27.3% and 40.9% respectively in the VAD-arm, which had no significant statistic difference (P >0.05).

CONCLUSION: The PR rate and OR rate of FMD-arm are significantly higher than in the VAD-arm in the treatment of refractory or relapsed multiple myeloma, but it took longer time to achieve PR. The regimen of FMD shows no significant renal or hepatic toxicity, it’s a safe and effective regimen in the treatment of refractory or relapsed multiple myeloma.