Results from a recent study conducted at the Mayo Clinic suggest that the de­gree of complete response a multiple myeloma patient achieves fol­low­ing a stem cell transplant may affect their survival.

In particular, the Mayo researchers found that the five-year overall survival rate was nearly twice as high for patients who achieved a stringent com­plete re­sponse (80 percent), compared to those who achieved a com­plete response (53 percent) or near com­plete response (47 percent).

However, the researchers point out that the achievement of a stringent complete response is only one of many markers that influence the prog­nosis of a myeloma patient. Other patient-related and disease-related factors, such as the durability of response, need to be considered. (These perspectives are echoed in a Beacon opinion column ^[1] written by one of the current study's co-authors, Dr. S. Vincent Rajkumar.)

Nevertheless, the study authors recommend that all future clinical trials report the share of patients who achieve a stringent complete response to better assess the efficacy of a treatment.

Background

According to the Mayo researchers, the share of patients who achieve deep responses to treatment has increased with newer myeloma therapies.

To take this development into account, the International Myeloma Working Group, which consists of mye­lo­ma experts from around the world, recently expanded the list of response criteria recommended for use in clinical trials to include the category of a stringent complete response.

The standard criteria for a complete response are the absence of monoclonal protein and less than 5 per­cent plasma cells in the bone marrow. A stringent complete response has the same criteria as a com­plete response, but also requires the absence of plasma cells in the bone marrow and a normal free light chain ratio, which can be determined using a free light chain assay.

However, according to the Mayo researchers, this new response category has not been validated in clinical trials yet, so its impact on outcomes is not clear.

The researchers therefore sought to assess the impact of specific subcategories of complete response (near complete response, complete response, and stringent complete response) on the outcomes of multiple myeloma patients who underwent early stem cell transplantation.

Study Design

Investigators from the Mayo Clinic analyzed data from 445 multiple myeloma patients who received an autologous (own) stem cell transplant within 12 months of being diagnosed with myeloma. All patients underwent transplantation between September 2002 and December 2008 at the Mayo Clinic.

The median age of the patients was 59 years. About 15 percent of the patients had what the authors label as "abnormal" chromosomal ab­nor­mal­i­ties; the authors do not specify, however, which chromosomal ab­nor­mal­i­ties these were.  Approximately two-thirds of the patients (63 percent) had stage 3 disease.

The majority of patients in the study received treatment with a novel myeloma therapy – such as thalidomide ^[2] (Thalomid) (33 percent), Revlimid ^[3] (lenalidomide) (23 percent), or Velcade ^[4] (bortezomib) (7 percent) – prior to transplantation.  Patients generally did not receive maintenance therapy after transplantation.

The median time from diagnosis to stem cell transplantation was six months.  The median follow-up time was 77 months after transplantation.

The treatment responses analyzed in the study were the best response achieved 60 days or longer after transplantation.

Study Results

Overall, 92 percent of patients responded to treatment, with 25 percent achieving a stringent complete re­sponse, 8 percent a complete response, 20 percent a near complete response, 14 percent a very good partial response, and 25 percent a partial response.

The median time to disease progression after transplantation for patients achieving at least a complete response was 39 months, compared to 20 months for patients achieving a very good partial response and 17 months for patients achieving a partial response.

When the researchers limited their analysis to patients achieving a complete response, they found that the median time to progression was significantly longer for patients who achieved a stringent com­plete re­sponse (50 months) compared to those who achieved a complete response (20 months) or a near com­plete response (19 months).

The median overall survival for all patients was 83 months from diagnosis.

From the time of transplantation, the median overall survival for patients achieving at least a complete re­sponse was 109 months, compared to 64 months for patients achieving a very good partial response and 59 months for patients achieving a partial response.

When the researchers limited their analysis to patients achieving a complete response, the median overall survival for patients who achieved a stringent complete response was also significantly longer (not yet reached) than the median overall survival of patients who achieved a complete response (81 months) or a near complete response (60 months).

The five-year overall survival rate was also significantly higher for patients achieving a stringent complete response (80 percent), compared to those who achieved either a complete response (53 percent) or near complete response (47 percent).

Other factors that affected overall survival after stem cell transplantation included whether or not a patient had abnormal chromosomal abnormalities and the patient's overall health.

For more information, please refer to the study in the Journal of Clinical Oncology ^[5] (abstract).