Researchers from the United Kingdom recently published a review in which they assess the role of kidney transplantation in multiple myeloma.

The authors conclude that, for certain multiple myeloma patients with kidney damage, kidney transplants should be considered more frequently than currently is the case.

Specifically, the researchers identify younger myeloma patients with end-stage kidney disease who require dialysis as the best candidates for a kidney transplant.

They point out that major improvements have been made in the treatment of multiple myeloma due to the introduction of new myeloma treatments. They add that extended periods of disease stabilization are currently possible allowing patients to live longer with the disease.

Based on these developments, the review authors recommend that kidney transplantation be considered early in the treatment process to maximize the benefits of the kidney transplant. They also advocate that the current recommended two-year waiting period between initial myeloma treatment and kidney transplants be reconsidered and adjusted based on the patient’s response to initial treatment.

Dr. Baldeep Wirk, a hematologist at the University of Florida who was not involved with the review, agrees with the British researchers’ assessment.

“Consideration of a [kidney] transplant should be made earlier in the treatment course of patients with end stage [kidney] disease and dialysis dependency than the current guidelines of a delay of up to two years from successful induction therapy,” she told The Beacon.

“Restoring kidney function would also allow an increase in the range and intensity of anti-myeloma therapy and thereby improve long-term survival,” she added.

However, the authors of the review point out that the role of kidney transplants in multiple myeloma still needs to be more clearly defined. Dr. Wirk once again agrees with the researchers’ assessment. “Due to its infrequent use, kidney transplantation in multiple myeloma should be tested in multicenter studies to define the optimal role and timing of kidney transplantation,” said Dr. Wirk.

In the meantime, the British researchers say emphasis should be put on the rapid management of kidney disease to avoid further complications.  

Kidney disease is a common myeloma-related complication. Previous studies have shown that high calcium levels and excess free light chains in the blood are two of the most common causes of kidney disease in myeloma patients (see related Beacon news). 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.

According to the review authors, kidney disease affects up to 50 percent of patients at some point during their disease. The British researchers point out that half of the patients recover from the complication. However, 2 percent to 12 percent of patients with kidney disease progress to end-stage kidney disease and require kidney replacement therapy.

Since the presence of kidney disease is associated with poor prognosis, the researchers note that prevention, stabilization, and reversal of the condition are the main goals for the management of kidney disease.

According to Dr. Wirk, “[Kidney] failure in multiple myeloma should be treated as a medical emergency.” She added that immediate diagnosis and treatment with Velcade (bortezomib)- and dexamethasone (Decadron)-based therapies, along with high-dose chemotherapy followed by stem cell transplantation and also maintenance therapy, could potentially restore function of the kidneys.

Treatment options for patients with end-stage kidney disease who require kidney replacement therapy include dialysis and kidney transplantation. In dialysis, the patient’s blood is pumped through an external machine which takes over the kidney’s function, i.e. it removes waste products from the blood.

According to the authors of the review, kidney transplants are rarely considered for myeloma patients, given the nature of the disease and the risk of post-transplant infections and disease recurrence.

In addition, the review authors point out that many myeloma patients on dialysis are elderly, frail, and have a limited life expectancy despite treatment. They are thus often ineligible for stem cell transplants and kidney transplants.

Nevertheless, the British researchers sought to better assess the impact and role of kidney transplants in myeloma patients.

They therefore reviewed and analyzed multiple studies that included a subset of myeloma patients who received kidney transplants.

A clinical study conducted in 1996 showed that nine myeloma patients who received a kidney transplant survived for 14 to 114 months. All patients showed improved quality of life and did not require dialysis after the transplant.

The authors also reviewed a European registry study, which included 2,430 myeloma patients, of which 1.4 percent received a kidney transplant. The median survival for the patients who had received a kidney transplant was 9.6 years.

In another study, seven multiple myeloma patients with end-stage renal disease underwent a combined stem cell and kidney transplant; 57 percent of the patients were myeloma-free for 4 to 12 years post transplant and 43 percent regained normal or near normal kidney function. Despite the encouraging results, the authors of the review think that the combined transplant is a highly specialized procedure that is unlikely to become routine clinical practice.

In another study reviewed by the researchers, 7 myeloma patients with light chain deposition disease in the kidneys (a condition in which high levels of light chains deposit in organs and damage them) received a kidney transplant. Overall, 71 percent of patients relapsed after a median of 33.3 months and 57 percent died.

However, the review authors point out that outcomes for patients with light chain deposition disease improve with the use of high-dose chemotherapy. They cite a 2008 study, which included two myeloma patients with light chain deposition disease who received kidney transplants 14 and 25 months after a stem cell transplant. The time to relapse was 35 and 69 months, respectively.

The researchers note that according to European guidelines, patients with light chain deposition disease are currently not eligible for kidney transplantation. However, they feel that the guidelines need to be reassessed given the progress that has been made recently in the treatment of this patient population.

For more information, please see the study in Nephron Clinical Practice (pdf).