Findings from a recent retrospective study conducted at the Mayo Clinic indicate that autologous stem cell trans­plan­ta­tion is an effective treat­ment option for multiple myeloma patients with advanced kid­ney disease.

The majority of patients (87 percent) responded to the treatment, with 40 percent achieving a complete response.  According to the researchers, this complete response rate is similar to those seen in other studies of stem cell trans­plan­ta­tion for myeloma patients with kid­ney disease.

However, the researchers found little evidence that trans­plan­ta­tion sig­nif­i­cant­ly improves kid­ney function in patients with advanced kid­ney dis­ease. Among the 15 patients in the study who were dialysis de­pen­dent prior to trans­plan­ta­tion, for example, only one became dialysis-independent after trans­plan­ta­tion

Based on these results, the researchers recommend that physicians be cautious about the expectations they create when discussing stem cell trans­plan­ta­tion with myeloma patients with advanced kid­ney dis­ease — particularly those on dialysis.  Patients should understand that trans­plan­ta­tion is unlikely to result in a significant improvement in kidney function.

In addition, the investigators recommend further studies to identify risk factors for the progression of kid­ney disease in myeloma patients who have under­gone a stem cell trans­plant.

Background

Kid­ney disease is a common myeloma-related complication that is present in approximately 10 percent to 40 percent of myeloma patients at the time of diagnosis and 25 percent to 50 percent of patients during the course of the disease.

Kid­ney impairment in myeloma patients is often caused by excess free monoclonal light chain proteins in the blood. Light chains are part of the structure of monoclonal proteins, which are antibodies present in high con­cen­tra­tions in myeloma patients. When light chains enter the blood stream unattached to the heavy chains, they are then referred to as free light chains and can impair kid­ney function.

In myeloma patients, kid­ney impairment leads to a higher risk of complications following treatment.

Due to the limited regenerative ability of cells in the kid­ney, a fast-acting myeloma treatment is needed to prevent further kid­ney damage and help the organ to recover.

Previous studies have shown that Velcade (bortezomib)-based regimens may reverse kid­ney damage in newly diagnosed myeloma patients (see related Beacon news).

However, according to the study investigators, the role of autologous stem cell trans­plan­ta­tion in the recovery of kid­ney function is uncertain.

An autologous transplant involves collecting a patient’s own stem cells before the patient receives high-dose chemotherapy, which destroys both healthy and cancerous cells. The stem cells are then re-infused into the patient to replace the destroyed cells.

Some studies have shown improvements in kid­ney function in a third of patients following trans­plan­ta­tion. In other studies, recovery of kid­ney function was poor.

To shed more light on the issue, the researchers assessed the effect of stem cell trans­plan­ta­tion on kid­ney function in patients with advanced kid­ney disease.

Study Design

Researchers from the Mayo Clinic retrospectively analyzed the records of 30 myeloma patients with advanced kid­ney disease who underwent autologous stem cell trans­plan­ta­tion at their institution between 2000 and 2010.

To be included in the analysis, patients had to be either dialysis-dependent or have creatinine levels above 3 mg/dL in the blood. Creatinine is a protein found in the body’s muscles. It is routinely removed from the blood by the kid­neys, but when the kid­neys are not functioning properly, creatinine cannot be easily removed and builds up in the blood.

The creatine-level cutoff of 3 mg/dL used in this study is higher than the 2 mg/dL cutoff frequently used in similar studies.  The Mayo researchers used the higher cutoff, however, because they wanted to focus on patients who are either on dialysis, or close to needing dialysis, because these patients are in particular need of treatments that might improve kid­ney function.

The median patient age was 61 years, and 50 percent of patients were dialysis-dependent at the time of trans­plan­ta­tion. The majority of the dialysis-dependent patients were undergoing dialysis three times a week before trans­plan­ta­tion.

Patients had received between one and three chemotherapy regimens before stem cell trans­plan­ta­tion; 3 percent of patients had previously achieved a complete response, 17 percent a very good partial response, and 27 percent a partial response. In addition, 37 percent had stable disease, and 13 percent had relapsed. Response to therapy was not reported for the remaining 3 percent.

At the time of trans­plan­ta­tion, the median estimated glomerular filtration rate (eGFR) was 12 mL/min/1.73 m² for all patients. Patients with low creatinine levels had higher eGFRs (15.0 mL/min/1.73 m²) than dialysis-dependent patients (8 mL/min/1.73 m²).

GFR measures the flow of fluid that is filtered through the kid­neys. Patients without kid­ney disease tend to have an eGFR of over 90 mL/min/1.73 m².

The median follow-up time was 41 months.

Results

Overall, 87 percent of patients responded to stem cell trans­plan­ta­tion, with 40 percent achieving a complete response, 33 percent a very good partial response, and 14 percent a partial response.

The median eGFR for all patients increased slightly from 12 mL/min/1.73 m² before trans­plan­ta­tion to 13.1 mL/min/1.73 m² after trans­plan­ta­tion.

For patients who had low creatinine levels but were dialysis-independent prior to stem cell trans­plan­ta­tion, their median eGFR increased noticeably, from 15 mL/min/1.73 m² prior to trans­plan­ta­tion to 19.4 mL/min/1.73 m² within the first three months following trans­plan­ta­tion. However, over the course of the study, 27 percent of these patients progressed to end-stage kid­ney disease and required dialysis as their myeloma progressed.

For patients who were dialysis-dependent prior to trans­plan­ta­tion, the median eGFR increased from 8 mL/min/1.73 m² to 11 mL/min/1.73 m² within three months of trans­plan­ta­tion. Although this increase was not considered statistically significant, 1 patient (6 percent of the dialysis-dependent patients) became dialysis-independent  17 days following trans­plan­ta­tion.

The researchers found that response to treatment, patient age, kid­ney function prior to trans­plan­ta­tion, and time from diagnosis to trans­plan­ta­tion were not associated with recovery of kid­ney function.

The overall survival rate was significantly higher in patients who were dialysis-independent at the time of trans­plan­ta­tion (69 months), compared to patients who were dialysis-dependent patients (29 months).

The most common side effects of trans­plan­ta­tion included mucositis (37 percent), central line blood infection (23 percent), and bacteria in the blood (17 percent).

For more information, please refer to the study in the journal Bone Marrow Transplantation (abstract).