Results from a recent study suggest that multiple myeloma patients whose monoclonal (M) protein levels continue to decrease after 100 days following stem cell trans­planta­tion may experience improved survival.

Both progression-free survival and overall survival were longer in patients who showed such a continued response without additional therapy after autologous stem cell trans­planta­tion (using their own cells).

“This study confirms the observation that the depth of response continues to improve after trans­plant,” said the study’s lead investigator Dr. Shaji Kumar from the Mayo Clinic. “It is of particular importance to patients who have a very good partial response, since many of them may go on to achieve a complete response without further therapy,” he added.

According to Dr. Kumar, the findings suggest that some patients may benefit from a wait-and-watch strategy after autologous stem cell trans­planta­tion, prior to consolidation or maintenance therapy.

Dr. Kumar and his colleagues also note that continued responses could prove to be a useful prognostic indicator in myeloma patients who undergo autologous stem cell trans­planta­tion.

However, Dr. Kumar cautions that the results from this retrospective study need to be confirmed by other prospective studies.

Background

Myeloma cells typically reside in a patient’s bone marrow. They produce large quantities of a specific type of protein called a monoclonal protein, or M protein. Successful treatment of myeloma leads to a reduction in M protein levels.

Autologous stem cell trans­planta­tion is commonly used as part of the treatment process for myeloma patients, particularly those who are younger and otherwise healthy.

In this process, healthy stem cells are isolated from the patient’s blood before high-dose chemotherapy is used to destroy the myeloma cells. The stem cells are then re-infused into the patient to replace the healthy cells destroyed during chemotherapy.

Patients are typically tested at 100 days after stem cell trans­planta­tion to evaluate the effectiveness of the therapy.

In previous studies, researchers have monitored M protein levels in trans­plant recipients beyond 100 days. Results from these studies suggest that, in some patients, the M protein levels continued to decline even after 100 days (without additional therapy). Such a decline has been termed a ‘continued response.’

In the current study, researchers investigated the clinical significance of continued responses.

Study Design

Researchers from the Mayo Clinic retrospectively analyzed data from 430 multiple myeloma patients who underwent autologous stem cell trans­planta­tion at the Mayo Clinic between 1999 and 2012.

Patients included in the current study had received a stem cell trans­plant within a year of diagnosis but did not achieve a complete response by 100 days after trans­planta­tion.

Patients in the study also did not receive a second stem cell trans­plant or main­te­nance therapy.

Study Results

Results from the study show that 39 percent of patients experienced a continued response after trans­planta­tion, in the absence of additional therapy. These patients achieved their best response at about nine months after trans­planta­tion.

Patients who experienced a continued response showed longer progression-free survival (2.9 years versus 1 year), time to next treatment (3.6 years versus 1.3 years) and overall survival (8 years versus 4.8 years) as compared to those without a continued response.

The share of patients who achieved a complete response via continued response was higher among patients who had reached a very good partial response at 100 days after trans­planta­tion (85 percent) than among those who had reached a partial response at 100 days (19 percent).

Factors that predicted a continued response included the production of a particular type of M protein called IgG, the presence of 3 percent or less of myeloma cells in the bone marrow at 100 days after trans­planta­tion, and a plasma cell disorder prior to the diagnosis of myeloma.

The authors of the study explain that the production of IgG-type M protein may predispose patients to a continued response because it is the most stable type of M protein, which means that it persists in the body longer than other M proteins, such as IgA or IgM. This could lead to a delayed drop in M protein levels after stem cell trans­planta­tion (and thus a continued response) in patients who have IgG-type M protein.

For further information, please see the study in Blood (abstract).