Light Chain–Induced Acute Renal Failure Can Be Reversed by Bortezomib-Doxorubicin-Dexamethasone in Multiple Myeloma: Results of a Phase II Study

Author:

Ludwig Heinz1,Adam Zdenek1,Hajek Roman1,Greil Richard1,Tóthová Elena1,Keil Felix1,Autzinger Eva Maria1,Thaler Josef1,Gisslinger Heinz1,Lang Alois1,Egyed Miklós1,Womastek Irene1,Zojer Niklas1

Affiliation:

1. From the Wilhelminenspital; University Hospital Vienna, Vienna; Private Medical University Hospital Salzburg, Salzburg; Hospital Leoben, Leoben; Hospital Wels-Grieskirchen, Grieskirchen; Hospital Feldkirch, Feldkirch, Austria; Masaryk University; Faculty Hospital Brno, Brno, Czech Republic; University Hospital L. Pasteur, Kosice, Slovakia; and Kaposi Mór Teaching Hospital, Kaposvar, Hungary.

Abstract

PurposeTo assess the efficacy of bortezomib-doxorubicin-dexamethasone (BDD) therapy in patients with multiple myeloma with light chain–induced acute renal failure.Patients and MethodsSixty-eight patients with light chain–induced acute renal failure and glomerular filtration rate (GFR) less than 50 mL/min received bortezomib (1.0 mg/m2on days 1, 4, 8, and 11), doxorubicin (9 mg/m2on days 1 and 4), and dexamethasone (40 mg on days 1, 4, 8, and 11); if well tolerated after two cycles, bortezomib could be increased to 1.3 mg/m2and doxorubicin administered on days 1, 4, 8, and 11.ResultsBy intent-to-treat analysis a myeloma response was obtained in 72% of 18 previously and 50 not previously treated patients (complete response [CR]/near CR [nCR], 38%; very good partial response [VGPR], 15%; partial response [PR], 13%; minor response [MR], 6%). Renal response was achieved in 62% of patients (renal CR, 31%; renal PR, 7%; renal MR, 24%). Median GFR increased from 20.5 to 48.4 mL/min. GFR improvement correlated with tumor response; the greatest increase to 59.6 mL/min was seen in the group of patients with CR/nCR/VGPR. Median progression-free survival was 12.1 months. One- and 2-year survival rates were 72% and 58%, respectively. Survival did not differ between patients with and without renal response but was inferior in previously treated patients (P < .001). In multivariate analysis, baseline GFR and tumor response correlated with renal response, and pretreatment status, lactate dehydrogenase, and myeloma response correlated with survival. The most common grade 3 or 4 toxicities were infection (19.1%), thrombocytopenia (14.7%), neutropenia (14.7%), fatigue/weakness (10.3%), and polyneuropathy (8.8%).ConclusionBDD induced a high rate of myeloma and renal responses, and treatment was well tolerated.

Publisher

American Society of Clinical Oncology (ASCO)

Subject

Cancer Research,Oncology

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