There have been two previous Total Therapy studies for multiple myeloma (MM) at the Myeloma Institute for Research There have been two previous Total Therapy studies for multiple myeloma (MM) at the Myeloma Institute for Research and Therapy (MIRT): Total Therapy I (from 1989 through 1994) and Total Therapy II (from 1996 to 2004). TT II used VDT-PACE for 4 cycles. Results have shown that patients treated on these studies had better outcomes (meaning patients have lived longer and had better responses to treatment) when compared to patients treated with standard chemotherapy. The newest incarnation is Total Therapy III, an ongoing study where Velcade is be incorporated.
As of April 2005, 162 patients were enrolled and these were compared to 314 comparable TTII patients who were enrolled on the Thalomid arm. First and second transplant on TT3 were completed faster, at medians of 3 and 5 months, compared to 5 and 10 months, respectively, in the TTII group. The probability of achieving ≥ near-CR (n-CR: only immunofixation positive) at 12 months was 81% with TT3 and 64% in TT2 (p=.001). Treatment-related mortality at 12 months was 4% with TT3 and 6% with TT2 (p=.3, the incorporation of Velcade upfront therefore appears to be more effective in inducing ≥ n-CR, but was associated with an increase in toxicity, especially in patients > 65 years. It is too early to assess OS and EFS and to determine if this approach impacts the outcome of patients with high risk features. However, the 2012 ASCO Educational Book supports DT and DVT as an induction regimen. It says on p. MS-11 that thalidomide is a Category 2 recommendation and mentions DVT as an acceptable choice, albeit with anti-coagulation.
Paul G Richardson, Constantine Mitsiades, Irene Ghobrial, Kenneth Anderson. (2006) Beyond single-agent bortezomib: combination regimens in relapsed multiple myeloma. Current Opinion in Oncology 18:6, 598-608
Robert Z Orlowski & Erik L Zeger Targeting the proteasome as a therapeutic strategy against haematological malignancies Expert Opinion on Investigational Drugs February 2006, Vol. 15, No. 2, Pages 117-130
Barlogie B, Anaissie E, van Rhee F, et al. Incorporating bortezomib into upfront treatment for multiple myeloma: early results of total therapy 3. British Journal of Haematology. 2007;138:176-185