Light chain-induced acute renal failure can be reversed by bortezomib-doxorubicin-dexamethasone in multiple myeloma: results of a phase II study.
OBJECTIVE
To assess the efficacy of bortezomib-doxorubicin-dexamethasone (BDD) therapy in patients with multiple myeloma with light chain-induced acute renal failure.


METHODS
Sixty-eight patients with light chain-induced acute renal failure and glomerular filtration rate (GFR) less than 50 mL/min received bortezomib (1.0 mg/m(2) on days 1, 4, 8, and 11), doxorubicin (9 mg/m(2) on 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/m(2) and doxorubicin administered on days 1, 4, 8, and 11.


RESULTS
By 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%).


CONCLUSIONS
BDD induced a high rate of myeloma and renal responses, and treatment was well tolerated.
Ludwig
Heinz
H
Department of Medicine I, Center of Oncology and Hematology, Wilhelminenspital, Vienna, Austria. heinz.ludwig@wienkav.at
Adam
Zdenek
Z
Hajek
Roman
R
Greil
Richard
R
Tóthová
Elena
E
Keil
Felix
F
Autzinger
Eva Maria
EM
Thaler
Josef
J
Gisslinger
Heinz
H
Lang
Alois
A
Egyed
Miklós
M
Womastek
Irene
I
Zojer
Niklas
N
D058186:Acute Kidney Injury / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality / Q000503:physiopathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001897:Boronic Acids / Q000008:administration & dosage; D000069286:Bortezomib; D003907:Dexamethasone / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D005060:Europe; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000276:immunology*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011480:Protease Inhibitors / Q000008:administration & dosage; D011719:Pyrazines / Q000008:administration & dosage; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
D000903:Antibiotics, Antineoplastic; D001897:Boronic Acids; D007147:Immunoglobulin Light Chains; D011480:Protease Inhibitors; D011719:Pyrazines; D000069286:Bortezomib; D003907:Dexamethasone; D004317:Doxorubicin