Reply to C.A. Hutchison et al
Authors: Meletios A. Dimopoulos, Evangelos Terpos
Journal: Journal of Clinical Oncology (2011)

We have read with interest the letter by Hutchison et al 1 regarding our consensus article 2 on renal impairment (RI) in patients with multiple myeloma (MM) that was published recently in Journal of Clinical Oncology on behalf of the International Myeloma Working Group.Hutchison et al commented that, in their opinion, our consensus statement failed to give emphasis to two key concepts: time to treatment and consideration of the severity of renal impairment.We do not agree with this statement.We have clearly stated in the consensus article that "cast nephropathy is the main cause of RI in MM (approximately 90% of cases) and is characterized by tubular atrophy and tubular-interstitial fibrosis" as a result of subsequent inflammation.Moreover, we have plainly indicated that "renal impairment reflects advanced disease and high tumor burden in patients with myeloma cast nephropathy," whereas "prognosis… remains tied to the reversibility of RI" in the majority of studies.Therefore, we strongly believe that it is crucial to begin treatment as soon as RI as a result of myeloma is diagnosed.To stress this point, in the abstract of the article, we mentioned that "rapid intervention to reverse renal dysfunction is critical for the management of these patients, especially for those with light chain cast nephropathy."We additionally suggested both supportive measures and systemic therapy based mainly on bortezomib but also on immunomodulatory drugs with high-dose dexamethasone for the rapid reduction of the production of monoclonal light chains, which is important for higher reversibility of RI.We also proposed the combination of bortezomib, thalidomide, and dexamethasone as a promising regimen for use in clinical trials to evaluate the possibility of an even greater reduction in the production of monoclonal light chains, and we recognized the promising value of high-cutoff hemodialysis on the rapid removal of free light chains, supporting its additional evaluation before widespread use in clinical practice.Thus, regarding the first point in the letter by Hutchison et al, 1 that is, the time to treatment, we think that it is obvious from our consensus article that treatment has to be begun immediately when myeloma-related RI is diagnosed.Regarding the second issue that the authors discuss in their letter, 1 the severity of RI, our consensus statement 2 mentions that treatment with bortezomib and dexamethasone can be administered with high efficacy to patients with acute renal failure or to patients with end-stage renal disease who require dialysis.Furthermore, our article describes novel criteria for the definition of renal reversibility, according to the initial renal dysfunction of the patient and on the basis of the novel classification of chronic kidney disorders.As mentioned in our article, we have to improve these criteria because the chronic kidney disorders classification has been validated only in patients with chronic RI and not in those with acute renal failure, which many patients with myeloma and cast nephropathy have.Therefore, we suggested that the RIFLE (risk, injury, failure, loss, end-stage kidney disease) criteria and Acute Renal Injury Network criteria have to be validated in MM.In conclusion, we believe that it is clear in our consensus statement that RI in myeloma needs rapid intervention and, according to the available data, bortezomib-based therapies are the treatment of choice for such patients.Efforts are needed to increase the incidence and depth of renal reversibility.The use of high-cutoff hemodialysis in combination with more effective therapies may improve our future therapeutic paradigm.Finally, we appreciate the paragraph by Hutchison et al 1 regarding the pathophysiology of RI in myeloma, which we were not able to incorporate in our article because of space restrictions.