Velcade^®, Thalidomide, Dexamethasone (VTD) Followed by Melphalan, Prednisone, Thalidomide (MPT) Maintenance as a First Line Treatment Demonstrates High Response Rates for High-Risk Patients with Multiple Myeloma (MM) Who Are Non-Transplant Candidates: Updated Results of Phase II Trial

VTD as well as MPT chemotherapies have been known to be most active regimens in patients (pts) with MM. The objective of this study is to evaluate response and toxicities and to estimate survival of pts with VTD followed by MPT, who are previously untreated non-transplant candidate patients with MM. A total of 35 pts were enrolled from March, 2006 through March, 2008. 14 pts were men and 21 pts were women. The median age was 67 years (range, 61–75 years) and median follow up was 12 months (range, 1–28 months). Pts received bortezomib (Velcade^®) 1.3 mg/m² on days 1, 4, 8, 11, thalidomide 100 mg daily, dexamethasone 40 mg on days 1–4 every 3 weeks for 6 cycles (VTD), thereafter, melphalan 4 mg/m² on days 1–7, prednisone 40 mg/m² on days 1–7, thalidomide 100 mg daily every 4 weeks for 12 cycles which has been modified later to 8 cycles as a consolidation therapy (MPT). Responses were assessed by EBMT criteria with additional nCR + VGPR. 26 out of 35 pts were analyzed for chromosomal aberrations by FISH on bone marrow at diagnosis. In 32 pts who completed at least first two cycles of VTD, 97% showed responses (16% CR, 3% nCR, 9% VGPR, 69% PR, 3% SD). 28 pts completed 4 cycles of VTD and they showed 100% response rates (32% CR, 18% nCR, 21% VGPR, 29% PR). 23 out of 24 who completed 6 cycles of VTD showed 96% responses (46% CR, 8% nCR, 17% VGPR, 25% PR). Also 15 pts who completed 4 cycles of MPT showed 93% responses (73% CR, 13% VGPR, 7% PR). Two-year PFS and OS were 67% and 73%, respectively. Cytogenetic abnormalities by FISH were detected in 17 (66%) out of 26 pts. The del(13), t(4;14), t(11;14), del(17p), and hyperdiploidy were present in 30%, 11%, 11%, 8%, and 20% of the pts, respectively. Factors such as del(13), t(4;14), or del(17p) were defined as high-risk factors, and the others were defined as standard-risk. 11 (42%) out of 26 pts were high-risk. Eleven pts with high-risk cytogenetics showed 100% response rates (8 CR and 3 PR) as well as 15 standard-risk pts showed 93% response rates (8 CR, 6 PR, and 1 PD). 17 pts (48%) could not finish planned therapy because of protocol violation (1 pt), consent withdrawal (2 pts), death (7 pts), disease progression (2 pts) and severe adverse reaction (5 pts). The causes of death were infection-related in 5 pts who were in remission, 2 pts with unknown etiology. Although peripheral neuropathy affected 90% of pts, only 14% of the pts were ≥grade 3. The most common side effects of the chemotherapies ≥ grade 3 were pneumonia (27%), herpes zoster (2%), asthenia (6%), diarrhea (9%), nausea (3%), thrombocytopenia (15%), neutropenia (15%) and anemia (12%). As a first-line therapy, VTD followed by MPT showed very high response rates even in pts with high-risk cytogenetics and manageable toxicities for nontransplant candidates. Although high dropout rate was observed due to complications such as infection and neuropathies, high-risk pts can get benefit from this treatment even in elderly population.