Findings from a retrospective study of stem cell transplantation among U.S. and Canadian multiple myeloma patients show that the technique has become more common in the past 15 years.

In addition, the outcomes associated with the procedure have improved over time.

“There was progressively improved survival for multiple myeloma patients managed with autologous stem cell transplantation as an initial therapy,” said Dr. Luciano Costa from the Medical University of South Carolina, who presented the results at the American Society for Hematology (ASH) annual meeting last month.

“Stem cell transplants have also remained safe,” he added.

However, Dr. Costa noted that changes over time in the way stem cell transplants are done are unlikely to have been responsible for the observed increase in survival among myeloma patients undergoing the procedure.

Instead, he argued that improvements in initial, pre-transplant (induction) therapy, combined with more effective post-relapse therapy, have probably contributed the most to improvements in survival among transplant recipients.

Based in part on the study findings, Dr. Costa recommended that stem cell transplantation and novel agents, such as thalidomide ^[1] (Thalomid), Velcade ^[2] (bortezomib), and Revlimid ^[3] (lenalidomide), be combined in the treatment of myeloma patients.

According to Dr. Costa, previous studies have not evaluated the contribution of autologous stem cell transplants to the observed increase in survival rates in myeloma patients.

Therefore, he and his colleagues analyzed data from the Center for International Blood and Marrow Transplant Research (CIBMTR) for 20,278 U.S. and Canadian myeloma patients who underwent autologous stem cell transplantation within 12 months of their diagnosis between 1995 and 2010.

In an autologous stem cell transplant, a patient’s own stem cells are collected before high-dose chemotherapy or radiation therapy. The stem cells are then reinfused into the patients to replace the healthy stem cells destroyed by the high-dose therapy.

Patients in Dr. Costa's study were divided into three groups based on the time when they received their transplant: 1995 to 1999 (2,226 patients), 2000 to 2004 (6,408 patients), and 2005 to 2010 (11,644 patients).

Dr. Costa pointed out that the median age of patients receiving a stem cell transplant soon after their diagnosis has increased over time from 54 years in the first time period to 58 years in the last time period. The share of patients receiving a transplant who were at least 65 years old rose from 8 percent in the first time period to 24 percent in the third time period.

However, the share of newly diagnosed patients over the age of 65 who receive a stem cell transplant soon after diagnosis has remained very low over the years.  The share was close to zero in the initial time period of Dr. Costa's study, and about 7 percent in the last time period.

In contrast, the share of newly diagnosed patients under the age of 65 receiving a stem cell transplant has increased noticeably over the past 15 years.

A Myeloma Beacon analysis of the data in Dr. Costa's presentation show that, in the first time period, about 14 percent of newly diagnosed patients under the age of 65 received a stem cell transplant within one year of diagnosis.  By the final period, this share reached about 30 percent.

There also has been a sizable increase in the share of patients under the age of 65 receiving a stem cell transplant at any point in their therapy (that is, not just within a year of diagnosis).  The Beacon's analysis indicates that this share has increased from about 22 percent in the first period to 40 percent in the last period.

Dr. Costa also noted that the data he and his colleagues collected show – not surprisingly – that the use of novel agents as initial therapy before stem cell transplantation has increased over the three time periods:  thalidomide (from less than 1 percent to 22 percent to 52 percent); Velcade (from 0 percent to 2 percent to 35 percent); and Revlimid (from 0 percent to 1 percent to 21 percent).

According to Dr. Costa, the increased use of novel agents has led to “better disease response prior to the stem cell transplant.”

Another trend regarding stem cell transplantation was the increased use over time of single-agent melphalan ^[4] (Alkeran) as the high-dose therapy prior to transplantation over the three time periods.

During the first period, 54 percent of patients had single-agent melphalan prior to transplantation.  In the second and third periods, this share increased to 93 percent and 99 percent, respectively.

Dr. Costa explained that melphalan has replaced both total body irradiation-based therapies and multi-drug regimens in recent years.

“To my surprise, there was also a decreased use of maintenance therapy” after transplantation, added Dr. Costa. The share of patients who received maintenance therapy decreased from 46 percent in the first group to 27 percent in the third group.

“However, there was a substantial change in agents [used for maintenance], from predominantly interferon in the first [group] to novel agents in the third [group],” he added.

As to overall survival among the patients in Dr. Costa's study, it increased over time. Five-year overall survival rates among patients receiving a transplant within a year of diagnosis increased from 47 percent in the first period, to 52 percent in the second, and to 55 percent in the third.

With regard to safety, Dr. Costa and his colleagues found that transplants were safe throughout the entire study period. Treatment-related mortality after 100 days, for example, was consistently low among patients in all three time periods, on the order of 1 to 2 percent.

For more information, please refer to abstract 596 ^[5] at the ASH 2012 meeting website as well as Dr. Costa's presentation slides ^[6], which he and the CIBMTR ^[7] have made available for download and viewing as a courtesy to the Beacon’s readers.