High CR and near-CR rate with bortezomib incorporated into up-front therapy of multiple myeloma with tandem transplants

Abstract

7519 Background: Tandem autotransplants have increased complete response (CR) rates and extended event-free survival (EFS) and overall survival (OS) in multiple myeloma (MM). Because of its remarkable efficacy in end-stage disease and to further increase CR and thereby improving EFS and OS, bortezomib (Velcade, V) was incorporated into Total Therapy 3 (TT3), both with DT-PACE combination chemotherapy (dex, thalidomide, cis-platin, adriamycin, cyclophosphamide, etoposide) as induction prior to and consolidation after transplant. Methods: TT3 has accrued 247 of a target population of 300 patients; median follow-up is 16 months. Twenty-seven percent of patients were 65 yr and older; cytogenetic abnormalities (CA) were present in 31% and inter-phase FISH-based deletion 13 in 42%. Results: Median times to 1st and 2nd transplants were 3 mo and 5 mo, with projected completion rates of 95% and 82%. The cumulative frequency of CR plus near-CR was 50% at 6 mo, 75% at 12 mo, reaching 80% at 18 mo. Blood stem cells were readily procured, yielding ≥20 million CD34 cells/kg in > 95%. At 12 mo, 91% are alive and 89% event-free. Relapse has occurred in 29 patients, whose distinguishing features included age ≥ 65 yr (48% vs 24%, p = .005), abnormal cytogenetics (CA, 48% vs. 29%, p = .03) and LDH > ULN (48% vs 23%, p = .004). Among 21 deaths, baseline features were: creatinine >4 mg/dL in 4; age ≥ 65 yr in 11; PS > 3 in 5 and PS > 2 in 4; CRP > 10 mg/L in 9 patients. Conclusions: Introducing V in TT3 as part of combination chemotherapy is safe, permits robust stem cell collection and induces remarkably high CR plus near-CR rates. High-risk MM features such as CA and LDH, defined in Total Therapies 1 and 2, also appeared detrimental with TT3. [Table: see text]