Results of a recent small German study indicate that high cut-off hemodialysis combined with chemotherapy may help restore kidney function in multiple myeloma patients with a serious form of kidney failure called acute kidney injury.

In addition, the researchers found that myeloma patients were more likely to recover kidney function if they received treatment soon after their kidneys began to fail.

Based on these results, Dr. Katja Weisel, one of the study investigators from the University of Tübingen, recommends that patients with dialysis-dependent acute kidney injury be treated as soon as possible in order to maximize their recovery potential.

“If dialysis-dependency lasts for more than three to five weeks, irreversible structural damage will occur in the kidney and the potential for kidney recovery is small,” Dr. Weisel told The Beacon. “With this knowledge, any effort should be undertaken early to diagnose and treat underlying causes of acute kidney injury.”

“We recommend that patients should immediately be seen by both a hematologist and a nephrologist [kidney specialist] to rapidly initiate chemotherapeutic treatment and optimize kidney protection. High cut-off hemodialysis might be an important tool in this setting,” she added.

These findings are being confirmed in an ongoing clinical trial in Europe.

“Currently, a prospective randomized trial is recruiting in Europe (EuLITE trial), which compares standard dialysis with high cut-off hemodialysis in parallel with chemotherapy in patients with [newly diagnosed] multiple myeloma and dialysis-dependent acute kidney injury,” said Dr. Weisel.

“If this trial can confirm the results [of the present study], [high cut-off hemodialysis] in parallel with chemotherapy could be a new standard treatment in multiple myeloma patients with dialysis-dependent acute kidney injury,” she said.

Dr. Weisel added that the results of the EuLITe trial are expected in 2013.

Acute kidney injury, characterized by a rapid decline in kidney function, is a common and potentially severe complication that affects up to 75 percent of all multiple myeloma patients.

Its main cause is the overproduction of antibody proteins called free light chains, which accumulate in the kidney and impair normal kidney function in myeloma patients.

Past studies have shown that acute kidney injury is associated with decreased response rates and overall survival in myeloma patients. Prior to recent advances in the treatment of myeloma, estimates of the median survival of patients with kidney failure ranged from 11 months to as low as 3 months.

“Until now, patients with multiple myeloma and dialysis-dependent acute kidney injury had a significantly impaired prognosis,” said Dr. Weisel.

With the introduction of the novel agents Velcade (bortezo­mib) and Revlimid (lenalidomide), the prognosis of myeloma patients with kidney failure began to improve.

More recently, high cut-off hemodialysis, a type of dialysis that removes free light chains from the blood, has also been shown to restore kidney function in patients with acute kidney injury (see related Beacon news).

The previous method of removing free light chains from the blood, called plasmapheresis, has not been shown to improve kidney function and overall survival in myeloma patients.

In the present study, researchers assessed the effectiveness of combining high cut-off hemodialysis with chemotherapy in recovering kidney function in multiple myeloma patients with acute kidney injury.

The study included 19 dialysis-dependent multiple myeloma patients with acute kidney injury, who were enrolled in the study between 2006 and 2009. The patients had a median age of 69 years. Fifty-three percent of patients had newly diagnosed myeloma, while the remaining 47 percent had relapsed or refractory myeloma.

All patients received five sessions of high cut-off hemodialysis within the first seven days of treatment, followed by one session every other day until their free light chain concentrations fell below 500 mg/L.

All patients also received chemotherapy in conjunction with high cut-off hemodialysis. Seventy-four percent of patients received Velcade-based regimens.

Of the 17 patients who completed treatment, 6 percent achieved complete kidney recovery, 29 percent achieved partial kidney recovery, and 47 percent achieved minor kidney recovery. Seventy-four percent of patients sustained kidney recovery. The median time from the start of therapy until the time that patients no longer required hemodialysis was 15 days.

The median time to free light chain reduction below 500 mg/L was 13 days with a median of six sessions of high cut-off hemodialysis. The time to free light chain reduction below 500 mg/L was significantly shorter for patients who achieved kidney recovery than patients who did not achieve kidney recovery (12 days versus 23 days).

The researchers found that the amount of time a patient had acute kidney injury prior to starting therapy was a predictor of kidney recovery. Patients who started therapy sooner were more likely to achieve kidney recovery than those who started therapy later.  The median duration of acute kidney injury was 2 days for those who achieved kidney recovery and 33 days for those who did not achieve kidney recovery.

After chemotherapy, 35 percent of patients achieved a partial response and 35 percent had stable disease.

Two early deaths occurred as a result of septic shock and progressive disease.

For more information, please see the article in the Annals of Hematology (abstract) or the EuLITE clinical trial description.