The addition of bortezomib (Velcade) to tandem transplantation as upfront therapy for multiple myeloma is safe and associated with high rates of complete and near complete response
ASCO The addition of bortezomib (Velcade) to tandem transplantation as upfront therapy for multiple myeloma is safe and associated with high rates of complete and near complete response, according to a study reported at the 2006 Annual Meeting of the American Society of Clinical Oncology (abstract 7519). The trial, Total Therapy 3 (TT3), is the third in a series attempting to integrate all active modalities in multiple myeloma, said lead author Bart Barlogie, MD, PhD, of the University of Arkansas for Medical Science. It built on Total Therapy 2 (TT2) by adding bortezomib, reducing the number of cycles of induction therapy from four to two, and using thalidomide (Thalomid) and dexamethasone to bridge drug-free intervals.
TT3 patients were treated with two induction cycles of VDT PACE (bortezomib, dexamethasone, thalidomide, cisplatin, Adriamycin, cyclophosphamide, etoposide); melphalan with tandem transplants 2 to 3 months apart; and two consolidation cycles with VDT PACE, with thalidomide/dexamethasone given during intervening periods. Maintenance therapy was bortezomib, thalidomide, and dexamethasone in year 2; thalidomide/dexamethasone in years 3 and 4.
Analyses compared the first 249 patients enrolled in TT3 with the 323 patients enrolled on the thalidomide arm of TT2 (TT2-Thal). Patients in both trials had symptomatic or progressive myeloma and were aged 75 years or younger. Median follow-up was 15 months in TT3 and 51 months in TT2-Thal.
Compared with patients in TT2-Thal, patients in TT3 had a higher CD34 yield and completed transplantation more rapidly (12-month estimated rate of completion of the second transplant, 84% vs 61%). TT3 patients had significantly higher 18-month cumulative rates of partial response (92% vs 83%) and near complete response (80% vs 69%), and a nonsignificantly higher cumulative rate of complete response (53% vs 45%).
The estimated 18-month treatment-related mortality was identical in the TT3 and TT2-Thal populations at 6%, even though patients in the new study were older, on average. The groups had nearly the same estimated 18-month event-free survival (83% vs 82%) and equivalent estimated overall survival (88%).
In a multivariate analysis of TT3 patients, significant determinants of event-free survival were LDH level ≥ 190 U/L (HR 4.1) and light-chain-only disease (0.3); for overall survival, LDH ≥ 190
U/L (7.2), creatinine 2 mg/dL or greater (2.9), and light-chain-only disease (0.2).
Compared with TT2-Thal, patients in TT3 (who received less thalidomide during induction) had a significantly lower incidence of grade 2 or higher thromboembolic events (27% vs 37%), syncope (2% vs 12%), constipation or bowel obstruction (7% vs 14%), tremor (3% vs 13%), and neuropathy (10% vs 16%). All received low-molecular-weight heparin and antibiotic prophylaxis.