Abstract
BACKGROUND: High-dose melphalan with autologous stem cell support improves survival when incorporated in the initial treatment of multiple myeloma. Published data show that induction thalidomide and dexamethasone (Thal/Dex) has a higher response rate than dexamethasone alone (Dex) or anthracycline induction (VAD or DVD), but the effect of initial induction therapy on outcomes after autologous transplant remains unclear.
PATIENTS: We reviewed the records of 164 patients who received high-dose melphalan with autologous stem cell support as part of initial therapy for multiple myeloma at the University of Pennsylvania. Median age was 55 years (range 25 – 72). Durie-Salmon stage at diagnosis was II in 27% and III in 70% of patients. Induction regimens included VAD (62%), DVD (12%), Thal/Dex (11%), Dex (5%), and more than one regimen (10%). Post-transplant therapies for consolidation or maintenance included thalidomide (7%), interferon (23%), tandem autologous transplant (4%), non-myeloablative allogeneic transplant (7%), autologous co-stimulated T-cell infusion (14%), or observation until progression (45%). Patients who received Thal/Dex initial therapy were not significantly different than those receiving anthracycline-containing induction regimens (VAD/DVD), except for lower serum creatinine (median 0.9 vs 1.1 mg/dl; p=0.01), with a trend toward lower beta-2 microglobulin (B2M) and correspondingly lower ISS stage.
RESULTS: Median overall follow-up is 29 months (range 7–120). Thal/Dex induction trended towards a higher Very Good Partial Response (VGPR) rate than anthracycline induction (29% vs 14%, p=NS) and a higher overall response rate (76% vs 68%, p=NS). All of the patients who received Thal/Dex as induction therapy are alive, with a median follow-up of 23 months (range 13 – 34), while overall survival in the anthracycline induction group is 85% at 2 years. Progression-free survival at 2 years is 93% for Thal/Dex induction and 58% for VAD/DVD (HR 0.12, p=0.039). The improvement in progression-free survival persists in Cox regression models that include creatinine and either B2M or ISS stage.
CONCLUSION: In myeloma patients who undergo autologous stem cell transplant, thalidomide and dexamethasone induction may result in improved progression-free survival compared with VAD or DVD. Further studies of initial therapies for myeloma should assess long-term outcomes after autologous transplant.
Progression Free Survival, By Initial Treatment
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