Our Total Therapy approach to treatment of multiple myeloma lies at the core of successful patient outcomes at the Myeloma Institute for Research and Therapy. The focus is on attacking myeloma on all fronts from the very beginning, applying a carefully crafted combination of available agents and treatment principles.
By closely monitoring patients’ responses to each trial and conducting detailed analyses of individual patients’ disease characteristics, we have designed a series of clinical trials that have shown steady, progressive improvements in patient outcomes. The graphs above show that the percentages of patients surviving and responding to therapy have increased as the trials have progressed from Total Therapy 1 to Total Therapy 2a, Total Therapy 2b, and Total Therapy 3.
Starting in 1989 with Total Therapy 1, we have designed and conducted a series of clinical trials that have each built on lessons learned from the previous trials. Thus, Total Therapies 2 and 3 have seen advances in patient survival and complete response that have resulted from incorporating new agents and adjusting therapies to support the stem-cell transplants.
Total Therapy 1 was the first clinical trial for multiple myeloma that included tandem auto-transplantation.*** The transition from Total Therapy 1 to Total Therapy 2 introduced more intensive therapy before transplantation, as well as chemotherapy after transplantation, and Total Therapy 2b added thalidomide to this regimen. Based on the positive results of Total Therapy 2b, Total Therapy 3 included thalidomide and also introduced bortezomib.
Throughout the progression of our Total Therapy trials, patients’ outcomes have steadily improved. The Total Therapy approach has resulted in an increase in median survival from 3 years to 6 years with Total Therapy 1, to about 10 years with Total Therapy 2, and to a projected 15 years with Total Therapy 3. We now are investigating whether the term “cure” is applicable and determining how to identify patients who meet the definition.
Total Therapy 4 and Total Therapy 5, initiated in late 2008, were the first myeloma treatment protocols at any facility to use risk-adapted therapy based on a robust predictive model built from gene expression profiling data. Total Therapy 4 is designed for patients with low-risk multiple myeloma and aims to reduce side effects while maintaining the superb outcomes achieved with Total Therapy 3. For patients with high-risk multiple myeloma, we designed Total Therapy 5 in an attempt to prevent or delay the relapses that so often overtake these patients.
We continue to develop our Total Therapy approach to treatment according to discoveries made through our extensive clinical and translational research program. Read more about Researching the Cure at the Myeloma Institute.
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Discoveries and Contributions of Total Therapy Trials
Total Therapy Publications
*Event-free survival: Survival without experiencing any myeloma-related event
**Complete response: No abnormal monoclonal proteins (M-proteins) in the blood serum or urine, disappearance of any soft-tissue plasmacytomas (malignant plasma cell tumors), less than 5% plasma cells in bone marrow
***Tandem auto-transplantation: consecutive transplants of a patient’s own stem cells