Findings from a retrospective study show that there have been significant changes in the treatment of newly diagnosed multiple myeloma patients in the United States since 1999.

In particular, more patients are being treated soon after diagnosis. In recent years, the use of novel agents, such as thalidomide (Thalomid), Velcade (bor­tezomib), and Revlimid (lenalidomide), and stem cell transplantation have be­come more common. At the same time, the use of conventional chemo­ther­a­py, such as melphalan (Alkeran), vincristine (Oncovin), and doxorubicin (Adria­mycin), as initial therapy has decreased.

The study investigators also found that the patient’s race and type of insurance impacted the type of initial treatment they received.

However, the investigators emphasize that this study only reflects trends in initial therapies for myeloma patients within the first 12 months of diagnosis. Further study is still required to understand changes in the treatment regimens for relapsed and refractory patients.

The investigators state that previous studies have not described how initial therapies have evolved over the past few decades and that the extent to which novel agents have replaced conventional chemotherapy was unknown.

Therefore, the researchers analyzed the records of 1,976 U.S. myeloma patients using the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) database. The researchers selected for analysis patients who were diagnosed in 1999 (524 patients), 2003 (710 patients), and 2007 (742 patients).

The median age at diagnosis for all three time periods ranged between 60 and 69 years. However, more than one-third of all patients were at least 70 years old.

The results of the analysis showed that fewer patients in the most recent time period delayed initial treat­ment of their myeloma.  The percentage of patients who received no treatment during the first year after their diagnosis fell from 29 percent in 1999 and 34 percent in 2003 to 19 percent in 2007.  The researchers explained that in 1999 treatment options for myeloma were limited and had significant side effects, which resulted in some patients choosing to delay treatment.

In addition, the results showed that the use of conventional chemotherapy only as an initial treatment sig­nifi­cantly decreased over time (from 57 percent to 23 percent to 5 percent).

In particular, the use of the chemotherapeutic agent melphalan alone decreased over the three time periods (from 32 percent to 12 percent to 4 percent).

The use of a combination of two other chemotherapy agents, vincristine and doxorubicin, also decreased over time (from 18 percent to 11 percent to 0.4 percent).

The investigators explained that the decline in chemotherapy use was accompanied by an increased use of novel agents, which reflects the increased efficacy and better tolerance for novel agents versus chemotherapeutic agents.

From 1999 to 2007, use of novel agents, either alone or as part of initial treatment, increased from 4 percent to 32 percent to 76 percent.

Specifically, thalidomide, which was approved by the U.S. Food and Drug Administration (FDA) for the treat­ment of newly diagnosed myeloma in 2006 but could be used earlier since it was approved for leprosy, became commonly used as part of initial treatment of myeloma starting in 2003 (from 4 percent to 31 per­cent to 36 percent).

Velcade, which was approved by the FDA for the treatment of relapsed and refractory myeloma in 2003 and newly diagnosed myeloma in 2008, increased in use from 2003 to 2007 (from 0.6 percent to 28 percent).

Since Revlimid was first approved by the FDA in 2006 for previously treated myeloma, only the patients from this study who were diagnosed in 2007 were initially treated with Revlimid (21 percent).

The investigators also note that although the use of stem cell transplantation within the first 12 months of diagnosis doubled over the timeframe studied, it still remained low.  Specifically, use of stem cell trans­plan­tation increased from 11 percent to 20 percent to 22 percent over the timeframe studied.

In addition, they determined that the combination of novel agents, chemotherapy, and a transplant became more common over time (from 0.6 percent to 8 percent to 18 percent).

The researchers gave two explanations as to why stem cell transplantation became more common over the timeframe studied.  The first explanation is that physicians began adopting older data showing that trans­plan­ta­tion may be better than chemotherapy.  The second is that new and effective novel agents allowed more patients with advanced myeloma to control their disease and become eligible for transplantation.  How­ever, they explained that the rate of trans­plan­ta­tion remained low in 2007 as it is still unknown whether it is best to do stem cell transplantation upfront or at the time of relapse.

These findings are similar to results from a previous study of trends in stem cell transplantation use (see related Beacon news). The investigators of that study specifically found that transplants have become more common in patients under the age of 65.

The results of the current study also showed that the patient’s type of insurance and race had an impact on whether they were likely to receive treatment with novel agents or stem cell transplantation.

For those who were Hispanic or not white, patients with private insurance were more likely to be treated with novel agents (47 percent) than those with Medicare only (38 percent) or Medicaid (36 percent).  Among the same patients, those with private insurance were also more likely to receive a stem cell transplant (17 per­cent) than those with Medicare only (6 percent) or Medicaid (4 percent).

The investigators stated that high out-of-pocket costs for Medicare patients who do not have supplemental insurance may explain their lower usage of costly novel agents.  They added that more research is needed to better understand why insurance and race impact treatment.

For more information, please refer to the study in the Journal of Clinical Oncology (abstract).