A recent study confirmed that the multi-drug regimen known as Total Therapy 3 (TT3) has a high response rate for newly diagnosed multiple myeloma patients. The study was conducted by physicians at the University of Arkansas Myeloma Institute for Research and Therapy and was published in the journal Blood.

The term “Total Therapy” indicates the use of all therapeutic agents and methods of treatment that have been shown to be effective against the disease. The Myeloma Beacon previously reported on a series of total therapies, including TT3, and the high success rates observed in those trials suggested that a cure for myeloma may be possible.

Total Therapy 3 combines a multi-drug regimen with stem cell transplants. Patients received two cycles of VTD-PACE, which consists of Velcade (bortezomib), thalidomide (Thalomid), dexamethasone (Decadron), and four-day continuous infusions of cisplatin, doxorubicin (Adriamycin), cyclophosphamide (Cytoxan), and etoposide. After undergoing two stem cell transplants with melphalan (Alkeran), patients received consolidation therapy with VTD-PACE and three years of maintenance therapy (with VTD in the first year and TD in the second and third years).

The first TT3 trial (2033-33) enrolled 303 patients with newly diagnosed myeloma, and it was reported to produce superior response rates in comparison to Total Therapy 2, its predecessor regimen that did not include Velcade.

In order to confirm these findings, an additional 177 patients were enrolled in a successor trial, TT3B (2066-66). The two TT3 protocols were similar, except that the TT3B trial employed Velcade as maintenance therapy for three years (instead of one) and Revlimid (lenalidomide) in place of thalidomide.

The two TT3 trials produced comparable clinical outcomes. Myeloma patients were classified as low-risk or high-risk based on abnormalities in their genes. In both trials, clinical outcomes differed between low-risk and high-risk myeloma patients.

Approximately 83 percent of patients were defined as low-risk myeloma patients, and these patients achieved superior clinical outcomes for overall survival, event-free survival, and complete response duration in both trials.

The authors of the study concluded that TT3 is a highly successful treatment option for low-risk myeloma patients. They predicted that 55 percent of low-risk patients would be cured, meaning that they would be able to maintain continuous complete remission for five years.

Dr. Bijay Nair and Dr. Bart Barlogie, two of the lead authors of the study, wrote in an email to The Myeloma Beacon, “As we gain better understanding of the mechanism of disease and discover better strategies to fight myeloma, we expect the cure fraction to increase over the coming years.”

The researchers also expect that TT3B will be better tolerated than TT3. “At this time, we have a median follow up of only 2 years on [TT3B], but we expect that with longer follow up, Revlimid will be a better tolerated drug than thalidomide, which can cause significant neuropathy [a form of nerve damage in the extremities that can cause pain and tingling sensations],” wrote Drs. Nair and Barlogie.

The authors noted that although the TT3 protocols have been generally well tolerated, “We are currently doing a randomized study (Total Therapy 4) to see if a lighter version of the TT3 protocol can provide comparable results.”

The TT4 regimen includes only one induction cycle before double transplants and only one consolidation cycle after transplantation. Identical to TT3B, the regimen includes three years of maintenance therapy with Velcade, Revlimid, and dexamethasone.

For those patients with high-risk myeloma (approximately 15 percent of patients), the issue is not achieving but sustaining complete response. The authors are currently investigating in Total Therapy 5 whether this problem may be addressed through lower doses that are given during more stages of the treatment.

The authors said, “The goal is to provide dose-dense rather than a dose-intense treatment to effectively eliminate the high-risk [myeloma]” and to prevent relapse.

For more information, please read the study in the journal Blood.

Update: Taking into consideration feedback from our readers, the title of this article was changed from “Multiple Myeloma Total Therapy Regimen Claims 50 Percent Cure Rate” to “Total Therapy Regimen May Be Highly Effective In Newly Diagnosed Myeloma Patients.”