patient care perspectives
Treatment of Patients With Multiple Myeloma and Renal Impairment
Overview
Renal impairment is common in patients with multiple myeloma. It stems from a variety of causes, and treatment must be approached carefully. Our featured expert discusses the most effective treatments to preserve renal function in patients with multiple myeloma.
Expert Commentary
Paul G. Richardson, MDClinical Program Leader and Director of Clinical Research |
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“Boronate peptide–based proteasome inhibitors have a favorable effect on the kidney, as do steroids. In fact, bortezomib-based therapy combined with steroids, cyclophosphamide, and adequate hydration is the treatment of choice for patients with multiple myeloma in the context of significant renal impairment.”
The persistent circulation of abnormal light chains and heavy chains is integral to multiple myeloma–related renal pathology, with myeloma cast nephropathy currently being the most common renal complication and immunoglobulin light chain amyloidosis becoming increasingly common as our patients live longer. Consequently, being attentive to preserving renal function is essential when making treatment decisions and in optimizing outcome.
Maintaining hydration is critical for protecting renal function in patients with multiple myeloma because these individuals are highly prone to dehydration and are vulnerable to vascular hypoperfusion—an effect that may contribute to a variety of complications, including neurotoxicity and other end-organ injury. Boronate peptide–based proteasome inhibitors have a favorable effect on the kidney, as do steroids. In fact, bortezomib-based therapy combined with steroids, cyclophosphamide, and adequate hydration is the treatment of choice for patients with multiple myeloma in the context of significant renal impairment. Oral ixazomib can cause gastrointestinal effects such as diarrhea, so care to avoid exacerbating renal impairment through dehydration is important. Carfilzomib must be used with caution in patients with significant renal impairment, as it can exacerbate renal dysfunction. Advising patients to be alert to other risks to their kidneys is also important. For example, a patient with multiple myeloma might be inclined to reach for nonsteroidal anti-inflammatory drugs for bone pain, but they can be hazardous in the setting of light chain production. In addition, vitamin C intake in excess of 500 mg per day can precipitate light chain deposition by acidifying the urine. Intravenous contrast for computed tomography imaging should be used with great caution, and this risk may be underappreciated in the emergency department and by less experienced radiologists. Hypercalcemia is less of an issue today than in the past, owing to the efficacy of bisphosphonates and to biologic antiresorptive agents such as denosumab. Denosumab has been revolutionary because it enables us to use bone-targeting therapy in patients with renal dysfunction without penalty; however, a significant issue that may arise is the potential for hypocalcemia. We have encountered admissions for profound hypocalcemia and even tetany in patients whose outside physicians had not been vigilant about tracking their calcium levels while on therapy.
References
Dimopoulos MA, Roussou M, Gavriatopoulou M, et al. Cardiac and renal complications of carfilzomib in patients with multiple myeloma. Blood Adv. 2017;1(7):449-454.
Gonsalves WI, Leung N, Rajkumar SV, et al. Improvement in renal function and its impact on survival in patients with newly diagnosed multiple myeloma. Blood Cancer J. 2015;5:e296.
Heher EC, Goes NB, Spitzer TR, et al. Kidney disease associated with plasma cell dyscrasias. Blood. 2010;116(9):1397-1404.
Oortgiesen BE, Azad R, Hemmelder MH, et al. The impact of the introduction of bortezomib on dialysis independence in multiple myeloma patients with renal impairment: a nationwide Dutch population-based study. Haematologica. 2018;103(7):e311-e314.
Raje N, Terpos E, Willenbacher W, et al. Denosumab versus zoledronic acid in bone disease treatment of newly diagnosed multiple myeloma: an international, double-blind, double-dummy, randomised, controlled, phase 3 study. Lancet Oncol. 2018;19(3):370-381.
