International Myeloma Working Group Recommendations for the Diagnosis and Management of Myeloma-Related Renal Impairment
The IMWG recommendations and information on the diagnosis and management of multiple myeloma-related renal impairment. It discusses the effectiveness and dose modifications of various drugs, including CC, high-dose corticosteroids, thalidomide, and lenalidomide, in improving renal function. The document also highlights the importance of using the International Myeloma Working Group criteria for defining renal response to treatment. It mentions the use of bisphosphonates and denosumab for managing hypercalcemia and the avoidance of nephrotoxic agents. Mechanical approaches such as plasma exchange and high-cutoff hemodialysis are also mentioned as potential treatment options. The document concludes with recommendations for the use of high-dose myeloablative therapy, autologous stem cell transplantation, and novel agents such as carfilzomib and ixazomib in patients with renal impairment.
Important Points:
- Systemic antimyeloma therapy should be initiated immediately to reduce toxic FLCs and improve renal function.
- CC and high-dose corticosteroids have been used for the management of patients with myeloma with renal impairment.
- Thalidomide does not require dose modification and can lead to renal recovery in 55-75% of patients with myeloma.
- Lenalidomide requires dose adjustments according to the degree of renal impairment and has shown improvement in renal function in 72% of patients.
- Dose modifications for various drugs used in the management of multiple myeloma with renal impairment are provided.
- Safety and survival outcomes vary depending on the drug and renal function.
- The IMWG criteria for renal response should be used in clinical trials and clinical practice.
- Adequate supportive care, including hydration and fluid monitoring, is mandatory for suspected myeloma-induced RI.
- Bisphosphonates can reduce calcium levels in hypercalcemia but should not be used in severe RI.
- Denosumab may be useful in hypercalcemia and RI but requires close monitoring of calcium levels.
- Nephrotoxic agents should be avoided in MM with RI.
- Plasma exchange and high-cutoff hemodialysis are mechanical approaches that can be considered for RI treatment.
- High-dose therapy with autologous stem cell transplantation (ASCT) is feasible and effective in patients with MM and RI.
- Carfilzomib and ixazomib show promise in the treatment of myeloma-related renal impairment.
- The diagnosis of RI in MM is based on elevated serum creatinine or reduced creatinine clearance.
- The CKD-EPI equation is recommended for evaluating renal function in MM patients.
- Proteinuria patterns and serum free light chain levels can provide clues to the etiology of RI.
- Renal biopsy may be necessary to exclude amyloidosis, MIDD, or other underlying conditions.
- The International Myeloma Working Group provides practical recommendations for the diagnosis and management of MM-related RI.
- Bortezomib-based regimens are recommended for the management of myeloma-related renal insufficiency.
- Lenalidomide, pomalidomide, and bortezomib-based regimens showed promising results in patients with MM and RI.
- High-dose dexamethasone should be administered for at least the first month of therapy.
- High-dose therapy with ASCT remains the treatment of choice for eligible patients with MM and is feasible in patients with RI.
- Melphalan dose needs to be adjusted in ASCT for patients with RI.
- Kidney transplantation in patients with MM and end-stage renal disease is limited in the literature.
Authors:
Giampaolo Merlini, Heinz Ludwig, Efstathios Kastritis, Hartmut Goldschmidt, Douglas Joshua, Robert Z. Orlowski, Raymond Powles, David H. Vesole, Laurent Garderet, Hermann Einsele, Antonio Palumbo, Michele Cavo, Paul G. Richardson, Philippe Moreau, Jesus San Miguel, S. Vincent Rajkumar, Brian G.M. Durie and Evangelos Terpos
Citation:
J Clin Oncol 34:1544-1557.
DOI: 10.1200/JCO.2015.65.0044