title: Impact of renal impairment on outcomes with lenalidomide and dexamethasone treatment in the FIRST trial, a randomized, open-label phase 3 trial in transplant-ineligible patients with multiple myeloma.
abstract: Renal impairment is associated with poor prognosis in myeloma. This analysis of the pivotal phase 3 FIRST trial examined the impact of renally adapted dosing of lenalidomide and dexamethasone on outcomes of patients with different degrees of renal impairment. Transplant-ineligible patients not requiring dialysis were randomized 1:1:1 to receive continuous lenalidomide and dexamethasone until disease progression (n=535) or for 18 cycles (72 weeks; n=541), or melphalan, prednisone, and thalidomide for 12 cycles (72 weeks; n=547). Follow-up is ongoing. Patients were grouped by baseline creatinine clearance into no (≥ 80 mL/min [n=389]), mild (≥ 50 to < 80 mL/min [n=715]), moderate (≥ 30 to < 50 mL/min [n=372]), and severe impairment (< 30 mL/min [n=147]) subgroups. Continuous lenalidomide and dexamethasone therapy reduced the risk of progression or death in no, mild, and moderate renal impairment subgroups vs. melphalan, prednisone, and thalidomide therapy (HR = 0.67, 0.70, and 0.65, respectively). Overall survival benefits were observed with continuous lenalidomide and dexamethasone treatment vs. melphalan, prednisone, and thalidomide treatment in no or mild renal impairment subgroups. Renal function improved from baseline in 52.6% of lenalidomide and dexamethasone-treated patients. The safety profile of continuous lenalidomide and dexamethasone was consistent across renal subgroups, except for grade 3/4 anemia and rash, which increased with increasing severity of renal impairment. Continuous lenalidomide and dexamethasone treatment, with renally adapted lenalidomide dosing, was effective for most transplant-ineligible patients with myeloma and renal impairment. Trial registration: ClinicalTrials.gov (NCT00689936); EudraCT (2007-004823-39). Funding: Intergroupe Francophone du Myélome and the Celgene Corporation.
authors.affiliation: National and Kapodistrian University of Athens, Athens, Greece mdimop@med.uoa.gr.
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authors.initials: MA
authors.lastname: Dimopoulos
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authors.affiliation: CHU Purpan/IUCT Oncopole, Toulouse, France.
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authors.affiliation: West China Hospital of Sichuan University, Chengdu, China.
authors.forename: Ting
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authors.affiliation: Arcispedale S. Maria Nuova, Reggio Emilia, Italy.
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authors.lastname: Gamberi
authors.affiliation: Hôpital Robert Debré, Paris, France.
authors.forename: Brigitte
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authors.affiliation: Staedtische Kliniken Frankfurt am Main Höchst, Frankfurt, Germany.
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authors.affiliation: National Cancer Center, Goyang-si Gyeonggi-do, South Korea.
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authors.forename: Pascal
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authors.forename: Richard
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authors.lastname: Van der Jagt
authors.affiliation: Hematology, Hôpital de Versailles, Le Chesnay, France.
authors.forename: Sophie
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authors.lastname: Rigaudeau
authors.affiliation: CHU Angers, Angers, France.
authors.forename: Mamoun
authors.initials: M
authors.lastname: Dib
authors.affiliation: Royal Bournemouth Hospital, Dorset, England, UK.
authors.forename: Rachel
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authors.lastname: Hall
authors.affiliation: Hospital Center, Vannes, France.
authors.forename: Henry
authors.initials: H
authors.lastname: Jardel
authors.affiliation: CHU Limoges, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Jaccard
authors.affiliation: Hôpital du Sacré-Coeur de Montréal, QB, Canada.
authors.forename: Axel
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authors.lastname: Tosikyan
authors.affiliation: Centre Hospitalier Lyon Sud, Pierre-Bénite, France.
authors.forename: Lionel
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authors.affiliation: Fred Hutchinson Cancer Center, Seattle, WA, USA.
authors.forename: William
authors.initials: W
authors.lastname: Bensinger
authors.affiliation: University Hospital VUB-Myeloma Center Brussels, Vrije Universiteit Brussels, Brussels, Belgium.
authors.forename: Rik
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authors.lastname: Schots
authors.affiliation: Celgene Corporation, Summit, NJ, USA.
authors.forename: Nicolas
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authors.lastname: Leupin
authors.affiliation: Celgene Corporation, Summit, NJ, USA.
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authors.lastname: Chen
authors.affiliation: Celgene Corporation, Summit, NJ, USA.
authors.forename: Jennifer
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authors.lastname: Marek
authors.affiliation: Celgene Corporation, Summit, NJ, USA.
authors.forename: Annette
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authors.lastname: Ervin-Haynes
authors.affiliation: Service des Maladies du Sang, Hôpital Claude Huriez, CHRU Lille, France.
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mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003404:Creatinine / Q000097:blood; D003907:Dexamethasone / Q000627:therapeutic use*; D018450:Disease Progression; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D000077269:Lenalidomide; D008297:Male; D008558:Melphalan / Q000627:therapeutic use; D008875:Middle Aged; D009101:Multiple Myeloma / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D011241:Prednisone / Q000627:therapeutic use; D011379:Prognosis; D011446:Prospective Studies; D051437:Renal Insufficiency / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D012720:Severity of Illness Index; D016019:Survival Analysis; D013792:Thalidomide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D013792:Thalidomide; D003907:Dexamethasone; D003404:Creatinine; D000077269:Lenalidomide; D008558:Melphalan; D011241:Prednisone