Total Therapy refers to our unique approach to myeloma treatment, which has formed the foundation for successful patient outcomes at the Myeloma Institute. It encompasses the concept of attacking myeloma on every front at the outset of treatment and utilizing novel combinations of all therapeutic agents and methods of treatment that have been shown to be effective against the disease. It has been the driving force behind our extensive research, incorporating a series of clinical trials that span well over two decades.
Over the years, Total Therapy has evolved as patient outcomes have been analyzed, new agents have become available, and specific nuances of myeloma biology have been identified.
Total Therapy 1, launched in 1989, introduced the use of tandem transplants. This was a novel and unique approach. Twenty percent of the 231 patients enrolled in Total Therapy 1, myeloma, are still alive today, in some cases up to 24 years since initial treatment.
Total Therapy 2, initiated in 1998, introduced randomized use of the controversial agent, Thalidomide. This was the first time that Thalidomide was used anywhere for the treatment of myeloma. Patients on Total Therapy 2 who received Thalidomide experienced a median survival of 9 years. This was a major breakthrough in the realm of myeloma treatment outcomes and set a new standard for treatment that was adopted by many other centers. Approximately 40 percent of the 668 patients enrolled in Total Therapy 2 are still alive today.
Total Therapy 3, begun in 2003, combined a multi-drug regimen that included the use of Velcade (a proteosome inhibitor, also known as bortezomib) in the induction, consolidation, and maintenance phases of the trial. This was in line with the “total’’ concept of applying all active therapeutic agents with the intent of developing curative treatment. The incorporation of Velcade resulted in superior response rates in comparison to Total Therapy 2. In addition, patients were classified as having low-risk or high-risk disease based on genomic abnormalities, with outcomes differing between the two groups. This newly-discovered ability to more specifically identify disease characteristics served as a launch pad, so to speak, for targeted, individualized treatments.
Indeed, our ultimate goal of developing the best tailored treatment plan that will cure myeloma patients based on the unique features of their disease has driven the design of our newest set of trials in the Total Therapy family. Total Therapy 4 for low-risk disease, Total Therapy 5 for high-risk disease, and Total Therapy 6 for previously treated but not transplanted disease build on the successes of our earlier applications of the Total Therapy approach.
Total Therapy 4 and Total Therapy 5, which began in 2008, were among the first for multiple myeloma or any other cancer to involve risk-specific treatment plans based on the genetic makeup of individuals’ myeloma cancer cells prior to being treated. Total Therapy 4 for patients with low-risk myeloma is basically a continuation of Total Therapy 3, but includes post, low-dose Melphalan Gene Expression Profiling analysis in order to help unravel Melphalan’s mechanism of action. For patients with high-risk myeloma, representing an estimated 15-20% of patients, Total Therapy 5 aims to provide dose-dense as opposed to dose-intense treatment to eradicate the high-risk myeloma and prevent relapse.
Total Therapy 6 is designed for those patients who have been previously treated but not transplanted. Again, we employ a dose-dense strategy in treating the myeloma. Early results have shown the method to be highly effective in low-risk patients. The time to achieve best response was faster in high-risk myeloma; however, the duration was shorter, substantiating the importance of maintaining a best response rather than depth of response in high-risk myeloma.
TT5B is the newest of the Total Therapy protocols. Unlike TT5, which incorporates the use of Velcade, TT5B uses Carfilzomib upfront and throughout all treatment phases (tandem transplants, inter-therapy, maintenance and consolidation). Inter-therapy cycles have been reduced from two to one to minimize prolonged thrombocytopenia. Carfilzomib is currently approved as a second line of therapy after relapse on Velcade. Carfilzomib is being used investigationally in TT5B. TT5B is a Phase II trial for high-risk myeloma.
We have clearly observed enormous success over the years with our Total Therapy Approach as described in our numerous publications. Our continued progress suggests that a cure for myeloma is, in fact, possible.
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 the Discoveries and Contributions of total therapy trials, as well as a list of Total Therapy Publications.
Read more about Researching the Cure at the Myeloma Institute
Excerpts from Myeloma Institute publication…
Improvement in long-term outcomes with successive Total Therapy trials for multiple myeloma: are patients now being cured?