TANDEM TRANSPANTATIONS DO NOT IMPROVE SURVIVAL IN MM

Tandem Transplantation Does Not Improve Survival in Multiple Myeloma

January 13, 2009 — Tandem autologous hematopoietic cell transplantation (AHCT) does not appear to improve overall survival or event-free survival in patients with multiple myeloma, according to a meta-analysis published online January 13 in the Journal of National Cancer Institute. Researchers found that when compared with single AHCT, the tandem procedure improved response rates but led to a statistically significant increase in treatment-related mortality.

Pooled evidence from clinical trials did not show a benefit for either overall survival or event-free survival among patients who received tandem transplantation. Based on these results, the study authors conclude that "the routine use of tandem transplant in its current form is not justified."

Single and tandem transplant are recommended as standard treatment in patients who are transplant candidates, explained lead author Ambuj Kumar, MD, MPH, assistant professor in Oncologic Sciences at Moffitt Cancer Center & Research Institute, in Tampa, Florida.

"New treatments may eventually minimize the role of single or double transplant," Dr. Kumar told Medscape Oncology. "However, tandem transplant is widely used in current practice, including in all the US Comprehensive Cancer Centers. To this effect, double transplant is recommended in the [National Comprehensive Cancer Network] 2008 treatment guidelines."

According to unofficial estimates by the Center for International Blood and Marrow Transplant Research (CIBMTR) (numbers used are not published estimates and were provided by CIBMTR directly to Moffitt researchers), 496 tandem transplants were undertaken in 2006 and 244 were undertaken in 2007, said Dr. Kumar.

Conflicting Results From Trials

AHCT as a treatment strategy for multiple myeloma has been evaluated in several randomized controlled trials, and initial studies demonstrated a survival advantage over conventional treatments, the authors note. A recent systematic review and meta-analysis, however, only showed a benefit for event-free survival, relative to conventional treatment. The more intense tandem AHCT approach was proposed as a strategy that could lead to further improvements in therapeutic outcomes, but clinical trials have thus far revealed conflicting results.

Because "decision making should not depend on the results from selective trials," Dr. Kumar and colleagues conducted a systematic review and meta-analysis to comprehensively evaluate the effect of tandem AHCT on event-free and overall survival.

A total of 6 randomized controlled trials, which consisted of 1803 patients, met the inclusion criteria. Data were available for the primary end points of overall survival and event-free survival from all of the included studies. When the results were pooled, there was no statistically significant benefit for overall survival for tandem AHCT, and the hazard ratio (HR) for patients treated with tandem transplant vs single transplant was 0.94. Pooled results for event-free survival were similar and showed no statistically significant survival benefit for tandem vs single transplant (HR, 0.86). There was statistically significant heterogeneity among all trials for overall survival and event-free survival.

The researchers did observe a better response rate with tandem AHCT, and this reached statistical significance (risk ratio, 0.79; P = .004). However, tandem AHCT was associated with a statistically significant increase in treatment-related mortality (risk ratio, 1.71)

The authors note that it is not yet known whether tandem AHCT improves overall survival in a subgroup of patients, or if a survival benefit will emerge as strategies to reduce treatment-related mortality are improved.

"As shown in the results, based on the totality of the existing evidence, tandem transplant cannot be justified," said Dr. Kumar. "There might be some patients who can benefit from this procedure, but this question can be addressed in either an individual patient-data meta-analysis or in the context of a well-designed and adequately powered prospective randomized controlled trial."