Patients under age 65 who undergo autologous stem cell transplantation early have significantly higher survival rates than patients who receive continued treatment with Revlimid and dexamethasone, according to a retrospective analysis of a recent clinical trial.

However, Dr. David Siegel, from the Hackensack University Medical Center in New Jersey and lead investigator of the study, pointed out that these results need to be interpreted cautiously, because the patients were not randomly selected to receive either an early or late stem cell transplant.

The results do suggest, however, that early transplantation may be beneficial for younger patients.  In addition, the results seem to call into question the commonly held belief that transplantation should be used more as a last resort in older patients.

“I think that we really have to seriously consider the role of transplant. As much as we think that we have data that obviates that, these observations would tend to argue against that. There is something to be said about early transplants,” said Dr. David Siegel, when he presented the study results at the American Society of Hematology annual meeting in Orlando last week.

Research has demonstrated that novel therapeutic agents, such as Revlimid ^[1] (lenalidomide) and Velcade ^[2] (bortezomib), significantly improve outcome for newly diagnosed multiple myeloma patients. Prior to the development of these agents, many myeloma patients underwent autologous stem cell transplantation as a frontline treatment.

Stem cell transplants involve collecting a patient’s stem cells from their blood. After undergoing high-dose chemotherapy, the patient receives the harvested stem cells back, which replace the cells that were damaged or destroyed in the chemotherapy process.

In order to determine the effect of early transplantation on patient outcome, Dr. Siegel and his colleagues analyzed the results of a recent clinical trial in which newly diagnosed myeloma patients were randomly assigned to one of two treatment arms: Revlimid with high-dose dexamethasone ^[3] (Decadron), called RD, or Revlimid with low-dose dexamethasone, abbreviated as Rd. After completing four treatment cycles, patients had the option to undergo an autologous stem cell transplant or to continue the assigned treatment.

An initial analysis of the data indicated that patients who underwent early stem cell transplantation, i.e. after four cycles of Revlimid-dexamethasone treatment, had a significantly higher three-year overall survival than patients who did not undergo early stem cell transplantation (92 percent versus 79 percent). 

In his presentation last week, Dr. Siegel showed data comparing the survival outcomes for three different patients groups: patients under age 65, patients ages 65 to 70, and patients over age 70.

For each age group, patients were subdivided into those who underwent early stem cell transplantation and those who did not.

For patients under the age of 65 who did not undergo early stem cell transplantation, the overall survival was 94 percent for one year, 88 percent for two years, and 78 percent for three years. For patients under age 65 who underwent early stem cell transplantation, the overall survival was 100 percent for one year, 94 percent for two years, and 94 percent for three years.

“I recognize and I emphasize that this is not randomized data. But this is a large patient population that was transplanted in the era of novel agents… Overall, there is a statistically significant advantage to early stem cell transplantation in patients under the age of 65,” said Dr. Siegel.

Although similar trends were observed in the age 65 to 70 and over age 70 groups, these results were not statistically significant, as the patient populations were smaller in these two groups.

In all age groups, the one-year patient survival was notably high across the board. However, the patient survival for patients treated with RD significantly decreased at two years if patients did not undergo early stem cell transplantation. This same drop in survival was noted for patients treated with Rd at three years if they did not undergo early stem cell transplantation.

In evaluating the differences in patient survival among the age groups, Dr. Siegel and his colleagues hypothesized that treatment-related deaths would be higher in the older age groups (age 65 to 70 and over age 70).

However, for patients age 65 to 70, there was little difference in the one-year survival rates (94 percent for no early stem cell transplantation versus 95 percent for early stem cell transplantation).

For patients over age 70, the one-year survival rates were also comparable between the two stem cell transplantation subgroups (92 percent for no early stem cell transplantation versus 100 percent for early stem cell transplantation). However, Dr. Siegel cautioned that the sample size for this population was extremely small (only six patients).

In noting that the selection bias of the stem cell transplantation subgroups limited the data analysis, Dr. Siegel and his co-authors emphasized a “need for randomized trials investigating the timing of autologous stem cell transplantation in myeloma in the era of novel therapy.”

For more information, please refer to abstract 38 ^[4] at the American Society of Hematology Meeting website.