Results of a recent small German study indicate that the level of residual myeloma cells in the bone marrow before stem cell transplantation may predict survival in multiple myeloma patients.

Specifically, the study authors found that patients with high levels of residual disease before transplantation had shorter progression-free and overall survival times than patients with low levels of residual disease.

They also found that a high level of residual disease after transplantation was associated with decreased progression-free survival, but not overall survival, in myeloma patients.

Based on these findings, they suggested that a goal of initial therapy in myeloma patients should be to achieve a low level of residual myeloma cells prior to high-dose chemotherapy and stem cell transplantation.

“[Our results suggest] that the goal of induction treatment should be complete remission,” said Dr. Roland Fenk of the Heinrich-Heine University in Duesseldorf, Germany, and one of the study authors.

“Thus, efforts should be undertaken to further improve the efficacy of induction treatment,” he added.

Dr. Edwin Alyea III of the Dana-Farber Cancer Institute in Boston, who was not involved in the study, agreed.

“[Patients] need to achieve the best [possible] response prior to proceeding [with stem cell transplantation],” Dr. Alyea told the Myeloma Beacon. He explained that this strategy would result in a better outcome after the transplant.

The disease prognosis of a myeloma patient often depends on whether the patient has advanced disease, chromosomal abnormalities, or achieved a complete response following therapy.

For instance, a past study has shown that despite achieving a complete response after therapy, patients who have residual disease (the presence of myeloma cells that are not destroyed by treatment) relapse earlier than patients without either of these risk factors (see related Beacon ^[1] news).

However, according to the study authors, further studies are needed to determine the reliability of residual disease in predicting the risk of relapse in myeloma patients.

In order to shed further light on this issue, German researchers investigated whether the level of residual disease before and after stem cell transplantation affected the survival times of myeloma patients after transplantation.

The study included 53 myeloma patients with a median age of 54 years.

All patients received initial treatment with idarubicin (Idamycin) and dexamethasone ^[2] (Decadron), followed by stem cell transplantation and maintenance therapy with either interferon alpha or thalidomide ^[3] (Thalomid).

Bone marrow samples were collected from all patients at diagnosis and also two to ten days before stem cell transplantation. Samples were also collected from 72 percent of patients three to six months after stem cell transplantation.

Prior to transplantation, 49 percent of patients had low residual disease (less than 0.2 percent residual disease). The other 51 percent of patients had high residual disease (more than 0.2 percent).

The researchers found that the patients who had low residual disease before transplantation had a longer estimated progression-free survival time than the patients who had high residual disease before transplantation (35 months versus 20 months)

After a median follow-up of 61 months, patients with low residual disease prior to transplantation also had a longer estimated overall survival time than the patients with high residual disease (70 months versus 45 months).

In addition, the researchers found that patients who had low residual disease after stem cell transplantation had a longer estimated progression-free survival time than patients who had high residual disease (32 months versus 20 months).

However, the overall survival time was similar between patients with low and high residual disease after transplantation.

Furthermore, patients who had high residual disease before transplantation but low residual disease after transplantation had a longer estimated progression-free survival time than patients who had high residual disease before and after transplantation (41 months versus 14 months).

The overall survival, however, was not different between these two groups of patients.

According to the study authors, these results show that while the residual disease level before transplantation is a strong predictor for both progression-free survival and overall survival, the residual disease level after transplantation predicts for progression-free survival but not overall survival. 

The study authors suggested further studies investigating the prognostic reliability of residual disease with novel agents instead of chemotherapy as the initial treatment for myeloma patients.

“Our results are from a past era of conventional treatment, so it is not clear if [we] can adopt the results [of our study] to current induction treatment with novel agents,” said Dr. Fenk.

For more information, please see the article in Biology of Blood and Marrow Transplantation ^[4] (abstract).