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

Meletios A. Dimopoulos, Matthew C. Cheung, Murielle Roussel, Ting Liu, Barbara Gamberi, Brigitte Kolb, H. Guenter Derigs, Hyeon Seok 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 SchotsNicolas Leupin, Guang Chen, Jennifer Marek, Annette Ervin-Haynes, Thierry Facon

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)363-370
Number of pages8
JournalHaematologica
Volume101
Issue number3
DOIs
Publication statusPublished - 2016

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Multiple Myeloma
Dexamethasone
Transplants
Kidney
Melphalan
Thalidomide
Prednisone
Therapeutics
lenalidomide
Exanthema
Disease Progression
Anemia
Dialysis
Creatinine
Safety
Survival

ASJC Scopus subject areas

  • Hematology

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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. / Dimopoulos, Meletios A.; Cheung, Matthew C.; Roussel, Murielle; Liu, Ting; Gamberi, Barbara; Kolb, Brigitte; Derigs, H. Guenter; Eom, Hyeon Seok; Belhadj, Karim; Lenain, Pascal; Van der Jagt, Richard; Rigaudeau, Sophie; Dib, Mamoun; Hall, Rachel; Jardel, Henry; Jaccard, Arnaud; Tosikyan, Axel; Karlin, Lionel; Bensinger, William; Schots, Rik; Leupin, Nicolas; Chen, Guang; Marek, Jennifer; Ervin-Haynes, Annette; Facon, Thierry.

In: Haematologica, Vol. 101, No. 3, 2016, p. 363-370.

Research output: Contribution to journalArticle

Dimopoulos, MA, Cheung, MC, Roussel, M, Liu, T, Gamberi, B, Kolb, B, Derigs, HG, Eom, HS, Belhadj, K, Lenain, P, Van der Jagt, R, Rigaudeau, S, Dib, M, Hall, R, Jardel, H, Jaccard, A, Tosikyan, A, Karlin, L, Bensinger, W, Schots, R, Leupin, N, Chen, G, Marek, J, Ervin-Haynes, A & Facon, T 2016, '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', Haematologica, vol. 101, no. 3, pp. 363-370. https://doi.org/10.3324/haematol.2015.133629
Dimopoulos, Meletios A. ; Cheung, Matthew C. ; Roussel, Murielle ; Liu, Ting ; Gamberi, Barbara ; Kolb, Brigitte ; Derigs, H. Guenter ; Eom, Hyeon Seok ; Belhadj, Karim ; Lenain, Pascal ; Van der Jagt, Richard ; Rigaudeau, Sophie ; Dib, Mamoun ; Hall, Rachel ; Jardel, Henry ; Jaccard, Arnaud ; Tosikyan, Axel ; Karlin, Lionel ; Bensinger, William ; Schots, Rik ; Leupin, Nicolas ; Chen, Guang ; Marek, Jennifer ; Ervin-Haynes, Annette ; Facon, Thierry. / 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. In: Haematologica. 2016 ; Vol. 101, No. 3. pp. 363-370.
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AU - Dimopoulos, Meletios A.

AU - Cheung, Matthew C.

AU - Roussel, Murielle

AU - Liu, Ting

AU - Gamberi, Barbara

AU - Kolb, Brigitte

AU - Derigs, H. Guenter

AU - Eom, Hyeon Seok

AU - Belhadj, Karim

AU - Lenain, Pascal

AU - Van der Jagt, Richard

AU - Rigaudeau, Sophie

AU - Dib, Mamoun

AU - Hall, Rachel

AU - Jardel, Henry

AU - Jaccard, Arnaud

AU - Tosikyan, Axel

AU - Karlin, Lionel

AU - Bensinger, William

AU - Schots, Rik

AU - Leupin, Nicolas

AU - Chen, Guang

AU - Marek, Jennifer

AU - Ervin-Haynes, Annette

AU - Facon, Thierry

PY - 2016

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N2 - 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.

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