The International Myeloma Working Group, a group of leading myeloma specialists, recently announced its recommendations for the treatment of multiple myeloma patients with kidney impairment. The group found that novel agents might improve - and possibly reverse - the complications of kidney impairment. In particular, the group recommended that patients with kidney impairment of any severity undergo treatment with Velcade plus dexamethasone, due to its safety and efficacy profile.

Diagnosis Of Kidney Impairment

Kidney impairment affects between 15 and 40 percent of multiple myeloma patients (please see the Beacon series on kidney impairment).

The most common method for assessing kidney function is by measuring the serum level of creatinine, a molecule that the kidneys are supposed to filter from the bloodstream. Patients are diagnosed with kidney impairment if the serum creatinine is higher than 2.0 mg/dL.

Since serum creatinine may depend on a patient’s age, sex, and muscle mass, the International Myeloma Working Group (IMWG) suggested that a more accurate analysis of kidney function may be assessed by the glomerular filtration rate (GFR).  The GFR measures the flow of fluid that is filtered through the kidneys.

Management Of Myeloma Patients With Kidney Impairment

In order to best improve kidney function, the IMWG recommended that myeloma patients with acute kidney failure stay adequately hydrated and receive treatment for potentially elevated serum calcium levels.

Additionally, the group discouraged the use of bisphosphonates (the standard treatment for myeloma bone disease) because they may increase serum calcium levels and further impair kidney function.

Other drugs that should be avoided include intravenous contrast dyes, certain diuretics and antibiotics, and nonsteroidal anti-inflammatory drugs, such as aspirin and ibuprofen.

In the case of severe kidney dysfunction, kidney replacement therapies, such as dialysis or transplant, may be required. The experts advised against plasma exchange as standard procedure for the treatment of kidney failure in myeloma patients. In plasma exchange, parts of the blood plasma are removed, treated, and returned to the patient’s blood circulation.

Treatment With Conventional Chemotherapy

The IMWG confirmed that conventional chemotherapy regimens may result in improved kidney function. In a study of 41 patients, kidney failure was reversed in 73 percent of patients who received treatment with high-dose dexamethasone (Decadron).

The experts recommended treatments containing cyclophosphamide (Cytoxan) or dexamethasone over melphalan (Alkeran)-containing treatment for patients with impaired kidney function because melphalan is primarily excreted by the kidneys. If melphalan is used, dosage should be reduced in patients with kidney impairment.

The group stated that high-dose chemotherapy with melphalan followed by autologous stem cell transplantation is possible in myeloma patients with kidney impairment. However, patients should be under 60 years old and in good health. They recommended that melphalan dosage be lowered from 200 mg/m² to 140 mg/m² in patients with kidney impairment. 

Treatment With Novel Agents

The group stated that the introduction of novel agents, such as Velcade (bortezomib), thalidomide (Thalomid), and Revlimid (lenalidomide), has improved survival rates for myeloma patients with kidney impairment, in some cases even reversing kidney damage.

They found Velcade to be an effective and safe therapy for patients with kidney impairment. Results from a Phase 2 trial demonstrated that 30 percent of patients with kidney impairment responded to Velcade treatment, compared to 45 percent of patients with normal kidney function. A second study suggested that acute kidney failure may be reversed with treatment of Velcade, doxorubicin (Adriamycin), and dexamethasone. Of the 58 patients, 42 responded to treatment, with three of the dialysis-dependent patients no longer needing dialysis.

Based on the available data, the recommended treatment for myeloma patients with kidney impairment is Velcade plus dexamethasone. The IMWG suggested that Velcade be administered at 1.3 mg/m² on days 1, 4, 8, and 11 of a 21-day cycle.

Dexamethasone should be given at a dose of 20 mg on the day of and the day after Velcade administration.

The IMWG also recommended the combination regimen of Velcade, melphalan, and prednisone as a first-line treatment for elderly patients with kidney impairment.

According to the IMWG, clinical trials of thalidomide in patients with kidney impairment have been promising, with one study demonstrating the reversal of kidney failure in 80 percent of patients treated with thalidomide and high-dose dexamethasone.

However, the IMWG cautioned against using thalidomide in patients with kidney impairment since there is limited data from randomized trials.

The IMWG stated that myeloma patients with kidney impairment may be treated with Revlimid.  However, because Revlimid is excreted primarily by the kidneys, reduced dosage is recommended.

Additionally, there is limited data for the efficacy of Revlimid-based regimens in patients with kidney impairment. The majority of Phase 2 and 3 studies with Revlimid exclude patients with serum creatinine levels above 2 mg/dL. However, it has been shown that patients with severe kidney impairment undergoing Revlimid-based treatment experienced an increased frequency of low platelet counts and had shorter overall survival than patients with normal kidney function.

While Revlimid at reduced dosage may be an effective treatment for patients with mild to moderate kidney impairment, the exact dosage is still being determined.

For more information, please read the article in the Journal of Clinical Oncology (abstract).