Findings from a recent analysis show that autologous (own) stem cell trans­plantation became significantly more common among North Ameri­can multiple myeloma patients between 1994 and 2005.

During that period, the rate of autologous stem cell transplantation across all myeloma patients increased fivefold, driven by a twentyfold increase in the num­ber of transplants carried out in myeloma patients as part of their initial therapy.

The findings also show that short-term overall survival for myeloma patients who received transplants in­creased significantly during the 12-year study period.

The results of the current study are in line with those of another recent study that found that stem cell trans­plantation has become more common among myeloma patients over the past 15 years, and that trans­plant outcomes have improved during that time (see related Beacon news).

The investigators note that various factors, such as patient selection, early identification of transplant can­di­dates, better supportive care, and better definition of optimal high-dose chemotherapy, may have con­tributed to the survival improvements seen in transplanted myeloma patients in the period covered by their study.

The study did not, however, investigate the use and impact of stem cell transplantation during the years since 2005, when novel myeloma treatments such as Revlimid (lenalidomide) and Velcade (bortezomib) largely supplanted the use of older, chemotherapy-based treatment regimens.

The researchers note that clinical trials are currently investigating the appropriate timing of stem cell trans­plants in the era of novel myeloma agents.

Background

Autologous stem cell transplantation is commonly used in the treatment of multiple myeloma.

Prior to a stem cell transplant, a patient is given high-dose chemo­therapy, which is intended to kill off as many of the patient's myeloma cells as possible.

The chemotherapy, however, also destroys most of the patient's healthy bone marrow cells.  Thus, stem cell transplantation using either the patient’s own stem cells (autologous transplantation) or stem cells from a donor (allogeneic transplantation) to repopulate the bone marrow with healthy cells.

For autologous stem cell transplantation, a patient’s stem cells are harvested prior to the high-dose chemo­therapy. They are then re-infused into the patient after chemotherapy to replace the healthy bone marrow cells that were destroyed.

Autologous stem cell transplants also are used in the treatment of other blood cancers and some solid-tumor cancers.  Indeed, the current study documents that, in the mid 1990s, the most common use of autologous stem cell transplantation was in the treatment of breast cancer (although transplants are rarely used for that purpose today).

In the current study, the investigators sought to assess the use of stem cell transplantation in the treatment of cancer over time in the U.S. and Canada, and to evaluate survival trends in patients who undergo stem cell transplantation in those countries.

Study Design

The authors of the new study retrospectively analyzed data reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) for 68,404 patients in the United States and Canada who received their first autologous stem cell transplant between 1994 and 2005.

The CIBMTR maintains an archive of stem cell transplant data which it and other affiliated organizations collect.  Data regarding autologous transplants are available for institutions in North and South American which have agreed, on a voluntary basis, to report data related to all autologous transplants they carry out.  The CIBMTR estimates that its participating U.S. institutions conduct approximately 65 percent of all autologous transplants performed each year in the country.

Because autologous transplantation is used in the treatment of many different cancers, the analysis in the current study includes data for patients with blood cancers – including multiple myeloma, non-Hodgkin lymphoma, acute myeloid leukemia – as well as solid tumors.

This article, however, focuses on the study results related to multiple myeloma.

Study Results

The study researchers found that the use of stem cell transplantation in multiple myeloma increased fivefold over the study period.

In 1994-1995, the number of U.S. myeloma patients who received autologous stem cell transplants was equal to about 5 percent of the number of newly diagnosed myeloma patients in the U.S. in those years.

By 2004-2005, the number of myeloma-related transplants in the U.S. had grown to equal about 25 percent of the number of newly diagnosed myeloma patients in the those years.

This increase in the rate of transplantation among myeloma patients was the greatest seen among all the diseases included in the study.

As a result, while myeloma patients comprised only 6 percent of the transplants in the author's database for the 1994-1995 period, they accounted for 44 percent of all transplants in the 2004-2005 period -- the largest share of any single disease.

At a superficial level, the increased rate of trans­plan­tation among myeloma patients between 1994 and 2005 was driven by a dramatic rise in transplants performed on myeloma patients as part of their initial therapy.

The authors estimate that the number of U.S. and Canadian myeloma patients who received a transplant as part of their initial therapy increased more than twentyfold between 1994-1995 and and 2004-2005.

This is reflected in a major change over time in the composition of U.S. and Canadian myeloma patients receiving transplants.

In the earliest period, less than a quarter of the myeloma patients receiving transplants were receiving them as part of their initial therapy.  By 2004-2005, in contrast, more than two thirds of the myeloma patients receiving transplants were receiving them as part of their initial therapy.

The authors go on to explain, however, that there likely is a deeper reason for the increased rate of trans­plan­tation among myeloma patients over the time period covered by their study.  They point, in par­ticu­lar, to the role of results from a French clinical trial published in 1996.  The trial, which involved newly diagnosed myeloma patients, demonstrated that four to six cycles of low-dose chemotherapy combined with stem cell transplantation led to improved response rates and overall survival compared to extended low-dose chemotherapy alone.

The authors of the current study also looked at short-term survival outcomes among the myeloma patients in their study.

They found that the one-year overall survival rate for myeloma patients who were in complete or partial remission at the time of transplantation increased over the study period from 83 percent in 1994-1995 to 92 percent in 2004-2005.

Older patients, in particular, experienced the greatest increase in this measure of survival over the study period. The one-year overall survival rate for myeloma patients who were 60 years or older and in complete or partial remission at the time of the transplant increased from 72 percent in 1994-1995 to 92 percent in 2004-2005.

For myeloma patients who were not in remission at the time of their autologous transplant, the one-year overall survival rate was not as high, but it also increased over the study period from 79 percent in 1994-1995 to 87 percent in 2004-2005.

Despite these increases in post-transplant survival rates, the researchers point out that ongoing clinical trials are investigating whether, in the age of novel myeloma therapies, transplantation should be included as part of the initial therapy myeloma patients receive.  The researchers also note, however, that at least one recent clinical trial has shown that early stem cell transplantation continues to improve treatment outcomes in newly diagnosed myeloma patients (see related Beacon news article).

For more information, please refer to the study in the journal Biology of Blood and Marrow Transplantation (abstract).

Note: A joint U.S.-French clinical trial is currently the key ongoing study investigating the issue of early versus delayed transplantation in newly diagnosed myeloma patients.  This retrospective study conducted at the John Theurer Cancer Center suggests early transplantation may still be beneficial in the age of novel anti-myeloma therapies.  In contrast, this Mayo Clinic study and a more recent study by researchers at Emory University suggest that delayed transplantation may be as effective, if not more effective, than upfront trans­plantation.