The International Myeloma Working Group (IMWG), a group of nearly 200 leading myeloma researchers from around the world who collaborate on a broad range of myeloma research projects, has issued an important warning to myeloma patients: Have an assessment for kidney function at diagnosis and at every follow-up visit.
MedPage Today offers an excellent summary of the guidelines. Here are excerpts:
The assessment should include the following: serum creatinine, estimated glomerular filtration rate (eGFR), electrolytes measurements, and, if available, free light chain, as well as electrophoresis of a sample from 24-hour urine collection.
"Prior studies have shown that the prognosis in myeloma is worse in patients who have renal failure than in those without," said recommendations co-author S. Vincent Rajkumar, MD, of the Mayo Clinic in Rochester, Minn. "The prognosis is worse even if renal failure is completely reversed. Some damage has already occurred to the kidney. The best thing is to try to prevent renal failure in the first place."
The process of diagnosis and evaluation begins with the recognition that renal impairment in myeloma can arise from a variety of causes. By far the most common cause is light chain cast nephropathy, resulting from myeloma-induced production and accumulation of monoclonal light chains on basement membranes of the glomeruli or renal tubule. Reducing the serum light chain concentration as soon as possible is essential for preventing or reversing renal impairment, Rajkumar said.
The IMWG-recommended strategy for renal reversibility includes high fluid intake and combination bortezomib-based antimyeloma therapy. The preferred combination is bortezomib, cyclophosphamide, and dexamethasone. A recommended alternative is bortezomib-thalidomide-dexamethasone.
The setting in which renal impairment occurs affects treatment choices. In patients with acute renal failure, drugs that are not renally excreted (such as thalidomide) are preferred over agents that are renally excreted, such as lenalidomide (Revlimid).
"If the patient has longstanding disease and we know the natural history, then we can adjust the drug dose in response to renal function because it's not an emergency situation," Rajkumar said. "In the acute setting, we want to reduce light chains as soon as possible, and we don't have time to adjust and determine the most appropriate dose."
The IMWG writing group characterized thalidomide as effective in patients with renal impairment and requiring no dose modifications, lenalidomide as effective and safe "mainly in patients with mild to moderate renal impairment." In patients with severe renal impairment or on dialysis, lenalidomide use requires "close monitoring for hematologic toxicity with dose reduction as needed."
The writing group did not address use of the recently approved monoclonal antibodies daratumumab (Darzalex) and elotuzumab (Empliciti).
The IMWG gave a qualified recommendation to the use of mechanical means to lower serum light chain levels, such as plasmapheresis or high-cutoff dialysis filters. The issue remains controversial because of a lack of clinical-trial evidence to support the techniques.
"I am very much in favor of plasma exchange or use of high-cutoff dialysis filters as soon as possible," Rajkumar said. "I think it is important to remove light chains quickly, and chemotherapy may take some time to work. Those few days could be critical, and we have to reverse the renal function. Randomized controlled trials are not in support of my position. In fact, they show the opposite, that plasma exchange does not help. My retort is that those trials were not sensitive enough, and this is a fairly benign procedure that can be done safely."
Renal impairment can influence a myeloma patient's suitability for stem cell transplantation. According to the IMWG, stem cell transplantation "is feasible even in patients who require dialysis." However, the procedure is associated with an increased mortality risk as compared with patients who have myeloma without renal impairment. Moreover, the procedure could increase the likelihood of dialysis in some patients.
"If a patient has elevated creatinine but doesn't require dialysis, we're very reluctant to take the patient to transplant," Rajkumar said. "We try as much as possible to reverse renal failure. Otherwise, we take a more conservative approach because we are worried that patients may be pushed into dialysis if we proceed to transplant. If a patient has chronic renal failure and is on chronic stable dialysis, we have been able to dose adjust chemotherapy and go to transplant without many problems."
about the author
Lizzy Smith was diagnosed with myeloma in 2012 at age 44. Within days, she left her job, ended her marriage, moved, and entered treatment. "To the extent I'm able, I want to prove that despite life's biggest challenges, it is possible to survive and come out stronger than ever," she says.