High-Cut Off Dialysis In Multiple Myeloma Patients With Dialysis Dependent Acute Renal Failure Shows Durable Renal Recovery: A Long-Term Follow Up Analysis

Acute kidney injury (AKI) either in primary diagnosis or at relapse is one of the frequent complications in multiple myeloma (MM). Myeloma cast nephropathy is induced by mechanical occlusion of the distal tubule by casts consisting of free light chains (FLC) and Tamm Horsfall protein. Impairment of renal function affects prognosis, with particularly poor outcomes in patients requiring hemodialysis with a historically reported median survival of 3-4 months. Introduction of novel therapeutic agents in MM therapy has improved MM response as well as renal outcome mainly due to a short time to initial response and consecutively reduction of the toxic FLC component. Extracorporeal light chain elimination in addition to chemotherapeutic treatment has been discussed controversially so far. We and others introduced the high-cut off (HCO) dialysis which allows effective elimination of FLC in an extended standard dialysis protocol. Recently, we demonstrated the efficacy of combined systemic and extracorporeal therapy regarding time to FLC reduction and renal recovery in a first case series of MM patients with dialysis-dependent AKI (Heyne et al., Ann Haematol 2012). Here, we report long-term renal outcome and overall survival data.

19 MM patients with dialysis dependent AKI were treated between November 2006 and October 2009 with HCO dialysis in parallel to systemic chemotherapy. The applied chemotherapy was chosen by the treating haematologist. All data was calculated by intent-to-treat (ITT) analysis. Progression-free survival (PFS) was analysed from the first day of HCO dialysis to progression or death, whichever occurred first. Overall survival was calculated from the first day of HCO dialysis to death. For statistical analysis GraphPad Prism (GraphPad Software Inc., La Jolla/CA, USA) and R (R Foundation for Statistical Computing, Vienna) biostatistical software was used.

The ITT cohort consisted of 19 patients. Median age was 69 (range 50-83) years. 10 patients had newly diagnosed, 9 relapsed or refractory MM. All patients had ISS stage III disease. Median serum FLC concentration at baseline was 8,580 (1 590-66 100) mg/L. Median serum creatinine was 6.8 (4.4-11.6) mg/dL, median eGFR 7.0 (3.3-10.9) mL/min/1.73m². Four (21%) early deaths occurred in the first three months of treatment, 2 patients with newly diagnosed and 2 patients with relapsed disease. Chemotherapy consisted mainly of bortezomib based regimens. As we reported previously, sustained renal recovery was achieved in 73.7% or 14/19 patients with a median time to independence of hemodialysis of 15 (4-64) days. In the long-term follow up analysis with a median follow-up of 62 months, 11/14 dialysis independent patients remained free of dialysis during further disease course. 3 patients again requiring dialysis all showed terminally refractory disease. Median PFS of the IIT population was 7.8 months for primary diagnosed and 4.8 months for relapsed and refractory patients, median OS of the whole population was 9.5 (range 2.8-not reached) months for primary diagnosed patients and 4.8 (range 1.0-19.8) months for the relapsed and refractory group.

Combination of systemic treatment and HCO dialysis in patients with myeloma cast nephropathy and dialysis dependent renal failure results in durable renal remissions in the majority of patients. Close monitoring of patients and early treatment intervention can prevent recurrent severe AKI in myeloma relapse. Survival data reflect the critically ill patient population with high tumor burden and high-risk of early death, but also show encouraging long-term myeloma and renal remissions. The benefit of the additional HCO dialysis in addition to conventional chemotherapy is currently investigated in a randomised multicenter trial (EuLITE study).