• Meletios A Dimopoulos, Matthew C Cheung, Murielle Roussel, Ting Liu, Barbara Gamberi, Brigitte Kolb, H Guenter Derigs, HyeonSeok Eom, Karim Belhadj, Pascal Lenain, Richard Van der Jagt, Sophie Rigaudeau, Mamoun Dib, Rachel Hall, Henry Jardel, Arnaud Jaccard, Axel Tosikyan, Lionel Karlin, William Bensinger, Rik Schots, Nicolas Leupin, Guang Chen, Jennifer Marek, Annette Ervin-Haynes, and Thierry Facon.
• National and Kapodistrian University of Athens, Athens, Greece mdimop@med.uoa.gr.
• Haematologica. 2016 Mar 1; 101 (3): 363-70.

AbstractRenal 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.Copyright© Ferrata Storti Foundation.

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