Lenalidomide and dexamethasone for acute light chain-induced renal failure: a phase II study.
We prospectively evaluated the activity and tolerance of lenalidomide-dexamethasone in 35 patients with acute light chain-induced renal failure. The lenalidomide dose was adapted to the estimated glomerular filtration rate and dexamethasone was given at high dose in cycle one and at low dose thereafter. Four patients died within the first two cycles, and five discontinued therapy leaving 26 patients for the per-protocol analysis. Responses were observed in 24/35 (68.6%) patients of the intent-to-treat population. Complete response was noted in seven patients (20%), very good partial response in three patients (8.6%), partial response in 14 patients (40%), and minimal response in one patient (2.9%). Renal response was observed in 16 (45.7%) patients: five (14.2%) achieved complete, four (11.4%) partial and seven (20%) minor renal responses. Five of 13 patients who were dialysis dependent at baseline became dialysis independent. The median time to myeloma and to renal response was 28 days for both parameters, while the median time to best myeloma and best renal response was 92 and 157 days, respectively. The median estimated glomerular filtration rate increased significantly in patients with partial response or better from 17.1 mL/min at baseline to 39.1 mL/min at best response (P=0.001). The median progression-free and overall survival was 5.5 and 21.8 months, respectively, in the intent-to-treat population and 12.1 and 31.4 months, respectively, in the per-protocol group. Infections, cardiotoxicity, anemia and thrombocytopenia were the most frequent toxicities. In conclusion, the lenalidomide-dexamethasone regimen achieved rapid and substantial myeloma and renal responses. The trial was registered under EUDRACT number 2008-006497-15.
Department of Medicine I, Wilhelminenspital, Vienna, Austria Heinz.ludwig@wienkav.at.
Heinz
H
Ludwig
Department of Medicine I, Wilhelminenspital, Vienna, Austria.
Elisabeth
E
Rauch
Department of Internal Medicine 4, Hospital Wels-Grieskirchen, Austria.
Thomas
T
Kuehr
University Hospital, Brno, Czech Republic.
Zdeněk
Z
Adam
Department of Medicine I, Wilhelminenspital, Vienna, Austria.
Adalbert
A
Weißmann
Department of Internal Medicine, Hospital Elisabethinen, Linz, Austria.
Hedwig
H
Kasparu
Department of Medicine I, Wilhelminenspital, Vienna, Austria.
Eva-Maria
EM
Autzinger
Department of Medicine I, Wilhelminenspital, Vienna, Austria.
Daniel
D
Heintel
Department of Internal Medicine III, Hospital Salzburg, Austria.
Richard
R
Greil
Department of Hemato-Oncology, University Clinic Leipzig, Germany.
Wolfram
W
Poenisch
Department of Medicine I, Wilhelminenspital, Vienna, Austria.
Ercan
E
Müldür
Department of Medicine I, Wilhelminenspital, Vienna, Austria.
Niklas
N
Zojer
D058186:Acute Kidney Injury / Q000139:chemically induced / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000139:chemically induced / Q000473:pathology; D003907:Dexamethasone / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007147:Immunoglobulin Light Chains; D007155:Immunologic Factors / Q000008:administration & dosage* / Q000009:adverse effects; D000077269:Lenalidomide; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality / Q000473:pathology; D006435:Renal Dialysis; D016019:Survival Analysis; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D013921:Thrombocytopenia / Q000139:chemically induced / Q000473:pathology; D016896:Treatment Outcome
D007147:Immunoglobulin Light Chains; D007155:Immunologic Factors; D013792:Thalidomide; D003907:Dexamethasone; D000077269:Lenalidomide