Maintenance therapy for remission in myeloma with Intron A following high- dose melphalan and either an autologous bone marrow transplantation or peripheral stem cell rescue

Eighty-four patients with myeloma were randomized to receive maintenance Intron A (Schering-Plough, Suffolk, UK), 3 mega units/m² s.c. three times weekly or no treatment following induction therapy with cyclophosphomide, vincristine, doxorubicin, methyl prednisolone (C-VAMP), consolidated with high-dose melphalan (HDM) 200 mg/m² + autologous bone marrow transplantation (ABMT). The patients have been followed up for a median of 52 months. Overall, median progression-free survival (PFS) from HDM was 27 months in the control group and 46 months in the Intron A group (<0.025). For the 65 patients who achieved complete remission (CR) with HDM, there was a significant prolongation of remission (p = 0.02) for those who received Intron A and 49% of these patients remained in remission four years after high-dose treatment. However, for partial responders (PR) and nonresponders to HDM there was no significant prolongation of PFS. Overall, survival was also significantly better for the Intron A group, with 5 deaths versus 14 deaths in the control group (p = 0.006). Subsequently, 54 consecutive patients received the same HDM followed by rescue with peripheral blood stem cells after induction chemotherapy which included C-VAMP. Intron A was started in 45 of these patients at a median of 62 days which was comparable to the ABMT arm. The overall response rate in these patients was 79.62% (43/54 - CR + PR) and the probability of survival at 18 months was 74.2% by the Kaplan Meier method. Of all the 138 patients analyzed above, 36 patients were previously untreated when seen by our institution; they received only C- VAMP induction treatment followed by HDM and either peripheral blood stem cell transplantation (PBSCT) (15 patients) or ABMT (21 patients), and then Intron A. The CR rate was 72% (26/36). There was no transplant related death and the actuarial disease free survival curve has plateaued at 60%. These patterns of response are now compatible to other successfully treated hematological malignancies such as AML. Strategies fur treatment should now be directed at improving complete remission rates still further and, as with AML, testing new treatment methods for translating these complete remissions into cures.