A randomized study (WOS MM1) comparing the oral regime Z‐Dex (idarubicin and dexamethasone) with vincristine, adriamycin and dexamethasone as induction therapy for newly diagnosed patients with multiple myeloma

Abstract

Summary Whilst infusional vincristine, adriamycin and dexamethasone (VAD) is an effective treatment for patients with multiple myeloma (MM), administration may be complicated by line‐associated infections and thromboses. The oral regime, Z‐Dex (idarubicin and dexamethasone) has been shown to be efficacious in MM. We conducted a randomized study comparing Z‐Dex with VAD as induction therapy in newly diagnosed MM patients. A total of 106 patients (median age, 56 years; range: 37–73; Durie‐Salmon stage II/III) were randomized to receive four to six cycles of Z‐Dex or VAD. Central line complications were reported in 38 patients on 57 cycles, primarily because of infection. Neutropenia (all grades) was more common in the Z‐Dex arm (P = 0·009) although grade III/IV neutropenia was not significantly different between the treatment groups (P = 0·06). Infections (all grades) were more commonly seen in the VAD arm (P = 0·001) although grade III/IV infections were not significantly different between the two groups (P = 0·081). The responses to therapy (complete/partial response) in evaluable patients were: VAD 74% vs. Z‐Dex 58%, with an estimated difference in response of 16% (95% CI −2–33, P = 0·075). VAD recipients (15%) suffered early treatment‐related mortality compared with 12% of Z‐Dex recipients. Overall, 45 patients have died: disease progression (Z‐Dex n = 13, VAD n = 10), regimen‐related toxicity (Z‐Dex n = 2, VAD n = 2), infection (Z‐Dex n = 0, VAD n = 3), other causes (Z‐Dex n = 7, VAD n = 2), unknown (Z‐Dex n = 3, VAD n = 2). This study demonstrated that Z‐Dex might be a suitable oral alternative to VAD for treating newly diagnosed MM patients, although definitive evidence for equivalence is not provided.

High rate of stem cell mobilization failure after thalidomide and oral cyclophosphamide induction therapy for multiple myeloma

“…Patients who had received induction therapy with CTD (n ¼ 67) were compared with a control group of patients (n ¼ 69) who had received VAD (n ¼ 41) or Z-Dex (oral idarubicin and dexamethasone; n ¼ 28) during the same period. The CTD regimen consisted of oral CY (500 mg on days 1, 8 and 15 (and day 22, if treated on a 28-day cycle)), thalidomide (100 mg daily for 3 weeks, then up to 200 mg daily) and dexamethasone (40 mg daily on days 1-4 and 12-15 (or [15][16][17][18], repeated every 21 (or 28) days). The VAD and Z-Dex regimens have been described previously.…”

“…The VAD and Z-Dex regimens have been described previously. 16 Patients who had received multiple previous therapies or thalidomide maintenance between the end of induction therapy and stem cell mobilization were not included. All mobilizations were performed with CY (2-4 g/m 2 ) and G-CSF from day 5 after CY until stem cell collection was completed.…”

MBL2 polymorphism and risk of severe infections in multiple myeloma patients receiving high-dose melphalan and autologous stem cell transplantation

“…[1][2][3] Morbidity and mortality due to infections during chemotherapy, adding further immunosuppression, are significant. [4][5][6] High-dose melphalan and autologous stem cell transplantation (ASCT) is the standard treatment for younger patients with MM. 7,8 Infections are very common during this treatment: up to 80% of patients have fever, and more than one third suffer from well-defined infections.…”

The treatment of the elderly multiple myeloma patients

“…In the first study, bortezomib was administered at three dose levels (1.0, 1.3 or 1.6 mg/m 2 ) on Days 1,4,15,22; melphalan at 6 mg/m 2 on Days 1 -5, prednisone at 60 mg/m 2 on Days 1 -5 (VMPT). TM was delivered at 50 mg on Days 1 -35.…”