Lenalidomide Plus Low-dose Dexamethasone in Chinese Patients with Relapsed or Refractory Multiple Myeloma and Renal Impairment

Overview

Journal Int J Hematol

Specialty Hematology

Date 2015 Mar 11

PMID 25753225

Citations 5

Authors

Dao-Bin Zhou

Li Yu

Xin Du

Jie Jin

Zhen Cai

Fangping Chen

Xiaoyan Ke

Xiao Li

Depei Wu

Fanyi Meng

Huisheng Ai

Jingshan Zhang

Dena DeMarco

Nianhang Chen

Jay Mei

Jianmin Wang

Jian Hou

Affiliations

Soon will be listed here.

Abstract

Lower starting doses of lenalidomide (LEN) are recommended for patients with renal impairment (RI). In the present study, we conducted a subgroup analysis of the MM-021 registration trial to investigate the efficacy and safety of LEN plus low-dose dexamethasone (LoDEX) in Chinese patients with advanced relapsed or refractory multiple myeloma (RRMM) based on levels of RI. Patients received LEN+LoDEX until disease progression or discontinuation. Patients were divided according to RI: no/mild [creatinine clearance (CrCl) ≥60 mL/min, n = 131], moderate (CrCl ≥30 to <60 mL/min, n = 54), and severe (CrCl <30 mL/min, n = 14). LEN starting dose was 25 mg/day on days 1-21, adjusted for baseline renal function. Best overall response rate was 48 %; in patients with no/mild, moderate, or severe RI, response rates were 50, 42, and 42 %, respectively. Median progression-free survival and overall survival were longer in patients with no/mild RI (9.3 and 22.4 months, respectively) versus those with moderate (6.9 and 16.0 months) or severe RI (4.8 and 11.1 months). LEN+LoDEX was well tolerated, although incidences of grade 3-4 neutropenia, anemia, and thrombocytopenia were higher in patients with severe RI. In Chinese patients with advanced RRMM and RI, adjusting the starting dose of LEN according to renal function did not compromise the efficacy or safety of LEN+LoDEX.

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References

Chen N, Wen L, Lau H, Surapaneni S, Kumar G . Pharmacokinetics, metabolism and excretion of [(14)C]-lenalidomide following oral administration in healthy male subjects. Cancer Chemother Pharmacol. 2011; 69(3):789-97. PMC: 3286592. DOI: 10.1007/s00280-011-1760-3. View

Dimopoulos M, Terpos E, Goldschmidt H, Alegre A, Mark T, Niesvizky R . Treatment with lenalidomide and dexamethasone in patients with multiple myeloma and renal impairment. Cancer Treat Rev. 2012; 38(8):1012-9. DOI: 10.1016/j.ctrv.2012.02.009. View

Dimopoulos M, Alegre A, Stadtmauer E, Goldschmidt H, Zonder J, de Castro C . The efficacy and safety of lenalidomide plus dexamethasone in relapsed and/or refractory multiple myeloma patients with impaired renal function. Cancer. 2010; 116(16):3807-14. PMC: 2970911. DOI: 10.1002/cncr.25139. View

Dimopoulos M, Christoulas D, Roussou M, Kastritis E, Migkou M, Gavriatopoulou M . Lenalidomide and dexamethasone for the treatment of refractory/relapsed multiple myeloma: dosing of lenalidomide according to renal function and effect on renal impairment. Eur J Haematol. 2010; 85(1):1-5. DOI: 10.1111/j.1600-0609.2010.01432.x. View

Dimopoulos M, Roussou M, Gkotzamanidou M, Nikitas N, Psimenou E, Mparmparoussi D . The role of novel agents on the reversibility of renal impairment in newly diagnosed symptomatic patients with multiple myeloma. Leukemia. 2012; 27(2):423-9. DOI: 10.1038/leu.2012.182. View

Roussou M, Kastritis E, Christoulas D, Migkou M, Gavriatopoulou M, Grapsa I . Reversibility of renal failure in newly diagnosed patients with multiple myeloma and the role of novel agents. Leuk Res. 2010; 34(10):1395-7. DOI: 10.1016/j.leukres.2010.04.024. View

Batuman V . The pathogenesis of acute kidney impairment in patients with multiple myeloma. Adv Chronic Kidney Dis. 2012; 19(5):282-6. DOI: 10.1053/j.ackd.2012.04.009. View

Abbott K, Agodoa L . Multiple myeloma and light chain-associated nephropathy at end-stage renal disease in the United States: patient characteristics and survival. Clin Nephrol. 2001; 56(3):207-10. View

Kyle R, Gertz M, Witzig T, Lust J, Lacy M, Dispenzieri A . Review of 1027 patients with newly diagnosed multiple myeloma. Mayo Clin Proc. 2003; 78(1):21-33. DOI: 10.4065/78.1.21. View

10.

Augustson B, Begum G, Dunn J, Barth N, Davies F, Morgan G . Early mortality after diagnosis of multiple myeloma: analysis of patients entered onto the United kingdom Medical Research Council trials between 1980 and 2002--Medical Research Council Adult Leukaemia Working Party. J Clin Oncol. 2005; 23(36):9219-26. DOI: 10.1200/JCO.2005.03.2086. View

11.

Iida S, Chou T, Okamoto S, Nagai H, Hatake K, Murakami H . Lenalidomide plus dexamethasone treatment in Japanese patients with relapsed/refractory multiple myeloma. Int J Hematol. 2010; 92(1):118-26. DOI: 10.1007/s12185-010-0624-7. View

12.

Dimopoulos M, Palumbo A, Attal M, Beksac M, Davies F, Delforge M . Optimizing the use of lenalidomide in relapsed or refractory multiple myeloma: consensus statement. Leukemia. 2011; 25(5):749-60. DOI: 10.1038/leu.2011.3. View

13.

Rajkumar S, Jacobus S, Callander N, Fonseca R, Vesole D, Williams M . Lenalidomide plus high-dose dexamethasone versus lenalidomide plus low-dose dexamethasone as initial therapy for newly diagnosed multiple myeloma: an open-label randomised controlled trial. Lancet Oncol. 2009; 11(1):29-37. PMC: 3042271. DOI: 10.1016/S1470-2045(09)70284-0. View

14.

Chen N, Kasserra C, Reyes J, Liu L, Lau H . Single-dose pharmacokinetics of lenalidomide in healthy volunteers: dose proportionality, food effect, and racial sensitivity. Cancer Chemother Pharmacol. 2012; 70(5):717-25. DOI: 10.1007/s00280-012-1966-z. View

15.

Weber D, Chen C, Niesvizky R, Wang M, Belch A, Stadtmauer E . Lenalidomide plus dexamethasone for relapsed multiple myeloma in North America. N Engl J Med. 2007; 357(21):2133-42. DOI: 10.1056/NEJMoa070596. View

16.

Dimopoulos M, Kastritis E, Rosinol L, Blade J, Ludwig H . Pathogenesis and treatment of renal failure in multiple myeloma. Leukemia. 2008; 22(8):1485-93. DOI: 10.1038/leu.2008.131. View

17.

Dimopoulos M, Terpos E, Chanan-Khan A, Leung N, Ludwig H, Jagannath S . Renal impairment in patients with multiple myeloma: a consensus statement on behalf of the International Myeloma Working Group. J Clin Oncol. 2010; 28(33):4976-84. DOI: 10.1200/JCO.2010.30.8791. View

18.

Eleutherakis-Papaiakovou V, Bamias A, Gika D, Simeonidis A, Pouli A, Anagnostopoulos A . Renal failure in multiple myeloma: incidence, correlations, and prognostic significance. Leuk Lymphoma. 2007; 48(2):337-41. DOI: 10.1080/10428190601126602. View

19.

Knudsen L, Hjorth M, Hippe E . Renal failure in multiple myeloma: reversibility and impact on the prognosis. Nordic Myeloma Study Group. Eur J Haematol. 2000; 65(3):175-81. DOI: 10.1034/j.1600-0609.2000.90221.x. View

20.

Hou J, Du X, Jin J, Cai Z, Chen F, Zhou D . A multicenter, open-label, phase 2 study of lenalidomide plus low-dose dexamethasone in Chinese patients with relapsed/refractory multiple myeloma: the MM-021 trial. J Hematol Oncol. 2013; 6:41. PMC: 3699390. DOI: 10.1186/1756-8722-6-41. View