Top

Published in:

01-01-2014 | Original Article

Lenalidomide with dexamethasone treatment for relapsed/refractory myeloma patients in Korea—experience from 110 patients

Authors: Kihyun Kim, Seok Jin Kim, Verena Voelter, Cheolwon Suh, Sung-Soo Yoon, Je-Jung Lee, Jae-Yong Kwak, Hun-Mo Ryoo, Yang Soo Kim, Joon Ho Moon, Seong Kyu Park, Sung-Hyun Kim, Yeung-Chul Mun, Jin Seok Kim, Hyeon-Seok Eom, Deog-Yeon Jo, Hyun Jung Jun, Ki-Hwan Kim, Jeong-Ok Lee, Jae Hoon Lee, Chang-Ki Min, Korean Multiple Myeloma Working Party (KMMWP)

Published in: Annals of Hematology | Issue 1/2014

Abstract

We conducted a retrospective analysis of lenalidomide with dexamethasone for patients with relapsed/refractory multiple myeloma (RRMM) who were treated within the Korean patient access program. Lenalidomide has been approved for RRMM for several years in Europe and North America, but has not been accessible to Asian patients in the past. Between 2008 and 2012, 110 patients from 20 hospitals were enrolled. The overall response rate (ORR) was 43.6 % with 15.4 % of very good partial response (VGPR) or better. The median time to progression (TTP) in this heavily pretreated patient population was 8.0 months, and median overall survival (OS) was 23 months. Hematologic toxicities, fatigue, anorexia, and constipation were the most common adverse events. The number of previous treatment lines, previous exposure to thalidomide, refractoriness to thalidomide and bortezomib, pretreatment white blood cell count (WBC), platelet count, t(14;16), and 17p deletion were significant prognostic factors for TTP, and creatinine clearance, refractoriness to thalidomide and bortezomib, performance status, platelet count, and 17p deletion were significant for OS in univariate analysis. In multivariate analysis, WBC and platelet count were significant prognostic factors for TTP and performance status for OS. For Korean myeloma patients, lenalidomide showed considerable efficacy, and toxicities were comparable to the data published in Europe and North America.

Quach H, Ritchie D, Stewart AK, Neeson P, Harrison S, Smyth MJ, Prince HM (2010) Mechanism of action of immunomodulatory drugs (IMiDS) in multiple myeloma. Leukemia 24(1):22–32. doi:10.1038/leu.2009.236 PubMedCrossRef

Zhu YX, Kortuem KM, Stewart AK (2013) Molecular mechanism of action of immune-modulatory drugs thalidomide, lenalidomide and pomalidomide in multiple myeloma. Leuk Lymphoma 54(4):683–687. doi:10.3109/10428194.2012.728597 PubMedCrossRef

Gandhi AK, Kang J, Capone L, Parton A, Wu L, Zhang LH, Mendy D, Lopez-Girona A, Tran T, Sapinoso L, Fang W, Xu S, Hampton G, Bartlett JB, Schafer P (2010) Dexamethasone synergizes with lenalidomide to inhibit multiple myeloma tumor growth, but reduces lenalidomide-induced immunomodulation of T and NK cell function. Curr Cancer Drug Targets 10(2):155–167PubMedCrossRef

Richardson PG, Blood E, Mitsiades CS, Jagannath S, Zeldenrust SR, Alsina M, Schlossman RL, Rajkumar SV, Desikan KR, Hideshima T, Munshi NC, Kelly-Colson K, Doss D, McKenney ML, Gorelik S, Warren D, Freeman A, Rich R, Wu A, Olesnyckyj M, Wride K, Dalton WS, Zeldis J, Knight R, Weller E, Anderson KC (2006) A randomized phase 2 study of lenalidomide therapy for patients with relapsed or relapsed and refractory multiple myeloma. Blood 108(10):3458–3464. doi:10.1182/blood-2006-04-015909 PubMedCrossRef

Dimopoulos M, Spencer A, Attal M, Prince HM, Harousseau JL, Dmoszynska A, San Miguel J, Hellmann A, Facon T, Foa R, Corso A, Masliak Z, Olesnyckyj M, Yu Z, Patin J, Zeldis JB, Knight RD (2007) Lenalidomide plus dexamethasone for relapsed or refractory multiple myeloma. N Engl J Med 357(21):2123–2132. doi:10.1056/NEJMoa070594 PubMedCrossRef

Weber DM, Chen C, Niesvizky R, Wang M, Belch A, Stadtmauer EA, Siegel D, Borrello I, Rajkumar SV, Chanan-Khan AA, Lonial S, Yu Z, Patin J, Olesnyckyj M, Zeldis JB, Knight RD (2007) Lenalidomide plus dexamethasone for relapsed multiple myeloma in North America. N Engl J Med 357(21):2133–2142. doi:10.1056/NEJMoa070596 PubMedCrossRef

Wang M, Dimopoulos MA, Chen C, Cibeira MT, Attal M, Spencer A, Rajkumar SV, Yu Z, Olesnyckyj M, Zeldis JB, Knight RD, Weber DM (2008) Lenalidomide plus dexamethasone is more effective than dexamethasone alone in patients with relapsed or refractory multiple myeloma regardless of prior thalidomide exposure. Blood 112(12):4445–4451. doi:10.1182/blood-2008-02-141614 PubMedCrossRef

Stadtmauer EA, Weber DM, Niesvizky R, Belch A, Prince MH, San Miguel JF, Facon T, Olesnyckyj M, Yu Z, Zeldis JB, Knight RD, Dimopoulos MA (2009) Lenalidomide in combination with dexamethasone at first relapse in comparison with its use as later salvage therapy in relapsed or refractory multiple myeloma. Eur J Haematol 82(6):426–432. doi:10.1111/j.1600-0609.2009.01257.x PubMedCentralPubMedCrossRef

Harousseau JL, Dimopoulos MA, Wang M, Corso A, Chen C, Attal M, Spencer A, Yu Z, Olesnyckyj M, Zeldis JB, Knight RD, Weber DM (2010) Better quality of response to lenalidomide plus dexamethasone is associated with improved clinical outcomes in patients with relapsed or refractory multiple myeloma. Haematologica 95(10):1738–1744. doi:10.3324/haematol.2009.015917 PubMedCrossRef

10.

Chanan-Khan AA, Lonial S, Weber D, Borrello I, Foa R, Hellmann A, Dimopoulos M, Swern AS, Knight R (2012) Lenalidomide in combination with dexamethasone improves survival and time-to-progression in patients >/=65 years old with relapsed or refractory multiple myeloma. Int J Hematol. doi:10.1007/s12185-012-1125-7 PubMedCentralPubMed

11.

Dimopoulos MA, Chen C, Spencer A, Niesvizky R, Attal M, Stadtmauer EA, Petrucci MT, Yu Z, Olesnyckyj M, Zeldis JB, Knight RD, Weber DM (2009) Long-term follow-up on overall survival from the MM-009 and MM-010 phase III trials of lenalidomide plus dexamethasone in patients with relapsed or refractory multiple myeloma. Leukemia 23(11):2147–2152. doi:10.1038/leu.2009.147 PubMedCrossRef

12.

Iida S, Chou T, Okamoto S, Nagai H, Hatake K, Murakami H, Takagi T, Shimizu K, Lau H, Takeshita K, Takatoku M, Hotta T (2010) Lenalidomide plus dexamethasone treatment in Japanese patients with relapsed/refractory multiple myeloma. Int J Hematol 92(1):118–126. doi:10.1007/s12185-010-0624-7 PubMedCrossRef

13.

Hou J, Du X, Jin J, Cai Z, Chen F, Zhou DB, Yu L, Ke X, Li X, Wu D, Meng F, Ai H, Zhang J, Wortman-Vayn H, Chen N, Mei J, Wang J (2013) 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 6(1):41. doi:10.1186/1756-8722-6-41 PubMedCentralPubMedCrossRef

14.

Durie BG, Harousseau JL, Miguel JS, Blade J, Barlogie B, Anderson K, Gertz M, Dimopoulos M, Westin J, Sonneveld P, Ludwig H, Gahrton G, Beksac M, Crowley J, Belch A, Boccadaro M, Cavo M, Turesson I, Joshua D, Vesole D, Kyle R, Alexanian R, Tricot G, Attal M, Merlini G, Powles R, Richardson P, Shimizu K, Tosi P, Morgan G, Rajkumar SV (2006) International uniform response criteria for multiple myeloma. Leukemia 20(9):1467–1473. doi:10.1038/sj.leu.2404284 PubMedCrossRef

15.

Rajkumar SV, Harousseau JL, Durie B, Anderson KC, Dimopoulos M, Kyle R, Blade J, Richardson P, Orlowski R, Siegel D, Jagannath S, Facon T, Avet-Loiseau H, Lonial S, Palumbo A, Zonder J, Ludwig H, Vesole D, Sezer O, Munshi NC, San Miguel J (2011) Consensus recommendations for the uniform reporting of clinical trials: report of the International Myeloma Workshop Consensus Panel 1. Blood 117(18):4691–4695. doi:10.1182/blood-2010-10-299487 PubMedCrossRef

16.

Rajkumar SV, Jacobus S, Callander NS, Fonseca R, Vesole DH, Williams ME, Abonour R, Siegel DS, Katz M, Greipp PR (2010) 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 11(1):29–37. doi:10.1016/S1470-2045(09)70284-0 PubMedCentralPubMedCrossRef

17.

Dimopoulos MA, Palumbo A, Attal M, Beksac M, Davies FE, Delforge M, Einsele H, Hajek R, Harousseau JL, da Costa FL, Ludwig H, Mellqvist UH, Morgan GJ, San-Miguel JF, Zweegman S, Sonneveld P (2011) Optimizing the use of lenalidomide in relapsed or refractory multiple myeloma: consensus statement. Leukemia 25(5):749–760. doi:10.1038/leu.2011.3 PubMedCrossRef

18.

Larson D, Kyle RA, Rajkumar SV (2012) Prevalence and monitoring of oligosecretory myeloma. N Engl J Med 367(6):580–581. doi:10.1056/NEJMc1206740 PubMedCrossRef

19.

Alegre A, Oriol-Rocafiguera A, Garcia-Larana J, Mateos MV, Sureda A, Martinez-Chamorro C, Cibeira MT, Aguado B, Knight R, Rosettani B (2012) Efficacy, safety and quality-of-life associated with lenalidomide plus dexamethasone for the treatment of relapsed or refractory multiple myeloma: the Spanish experience. Leuk Lymphoma 53(9):1714–1721. doi:10.3109/10428194.2012.662643 PubMedCrossRef

20.

Alegre A, Aguado B, Giraldo P, Rios E, Canovas A, Ibanez A, Castillo I, Hernandez MT, Oriol A, Palomera L, Rodriguez JN, Garcia FL, Calvo JM, Martinez-Chamorro C, de la Serna J, Lahuerta JJ (2011) Lenalidomide is effective as salvage therapy in refractory or relapsed multiple myeloma: analysis of the Spanish Compassionate Use Registry in advanced patients. Int J Hematol 93(3):351–360. doi:10.1007/s12185-011-0785-z PubMedCrossRef

21.

Avet-Loiseau H, Soulier J, Fermand JP, Yakoub-Agha I, Attal M, Hulin C, Garderet L, Belhadj K, Dorvaux V, Minvielle S, Moreau P (2010) Impact of high-risk cytogenetics and prior therapy on outcomes in patients with advanced relapsed or refractory multiple myeloma treated with lenalidomide plus dexamethasone. Leukemia 24(3):623–628. doi:10.1038/leu.2009.273 PubMedCrossRef

22.

DU X, JIN J, CAI Z, CHEN F, ZHOU DB, YU L, KE X, LI X, WU D, MENG F, AI H, WANG J, ZHANG J, MEI J, HOU J (2013) Efficacy and safety of lenalidomide 25 mg + low-dose dexamethasone in Chinese patients with relapsed/refractory myeloma. Clin Lymphoma Myeloma Leuk 13(s1):s145

23.

Guglielmelli T, Bringhen S, Rrodhe S, Gay F, Cavallo F, Berruti A, Montefusco V, Piro E, Benevolo G, Petrucci MT, Caravita T, Offidani M, Corradini P, Boccadoro M, Saglio G, Palumbo A (2011) Previous thalidomide therapy may not affect lenalidomide response and outcome in relapse or refractory multiple myeloma patients. Eur J Cancer 47(6):814–818. doi:10.1016/j.ejca.2010.12.026 PubMedCrossRef

24.

Carrier M, Le Gal G, Tay J, Wu C, Lee AY (2011) Rates of venous thromboembolism in multiple myeloma patients undergoing immunomodulatory therapy with thalidomide or lenalidomide: a systematic review and meta-analysis. J Thromb Haemost 9(4):653–663. doi:10.1111/j.1538-7836.2011.04215.x PubMedCrossRef

25.

Menon SP, Rajkumar SV, Lacy M, Falco P, Palumbo A (2008) Thromboembolic events with lenalidomide-based therapy for multiple myeloma. Cancer 112(7):1522–1528. doi:10.1002/cncr.23336 PubMedCentralPubMedCrossRef

26.

Niesvizky R, Martinez-Banos D, Jalbrzikowski J, Christos P, Furst J, De Sancho M, Mark T, Pearse R, Mazumdar M, Zafar F, Pekle K, Leonard J, Jayabalan D, Coleman M (2007) Prophylactic low-dose aspirin is effective antithrombotic therapy for combination treatments of thalidomide or lenalidomide in myeloma. Leuk Lymphoma 48(12):2330–2337. doi:10.1080/10428190701647887 PubMedCrossRef

27.

Koh Y, Bang SM, Lee JH, Yoon HJ, Do YR, Ryoo HM, Lee N, Kim SJ, Kim K, Yoon SS, Won JH, Mun YC, Lee MH, Rhee KH, Kim HJ, Eom H, Kim MK, Shin HC (2010) Low incidence of clinically apparent thromboembolism in Korean patients with multiple myeloma treated with thalidomide. Ann Hematol 89(2):201–206. doi:10.1007/s00277-009-0807-6 PubMedCrossRef

28.

Wu SY, Yeh YM, Chen YP, Su WC, Chen TY (2012) Low incidence of thromboembolism in relapsed/refractory myeloma patients treated with thalidomide without thromboprophylaxis in Taiwan. Ann Hematol 91(11):1773–1778. doi:10.1007/s00277-012-1506-2 PubMedCrossRef

29.

Touzeau C, Blin N, Clavert A, Roland V, Loirat M, Tessoulin B, Le Gouill S, Planche L, Pennetier M, Mahe B, Mohty M, Malard F, Peterlin P, Dubruille V, Moreau P (2012) Efficacy of lenalidomide plus dexamethasone in patients older than 75 years with relapsed multiple myeloma. Leuk Lymphoma 53(7):1318–1320. doi:10.3109/10428194.2011.654116 PubMedCrossRef

30.

Klein U, Jauch A, Hielscher T, Hillengass J, Raab MS, Seckinger A, Hose D, Ho AD, Goldschmidt H, Neben K (2011) Chromosomal aberrations +1q21 and del(17p13) predict survival in patients with recurrent multiple myeloma treated with lenalidomide and dexamethasone. Cancer 117(10):2136–2144. doi:10.1002/cncr.25775 PubMedCrossRef

31.

Dimopoulos MA, Kastritis E, Christoulas D, Migkou M, Gavriatopoulou M, Gkotzamanidou M, Iakovaki M, Matsouka C, Mparmparoussi D, Roussou M, Efstathiou E, Terpos E (2010) Treatment of patients with relapsed/refractory multiple myeloma with lenalidomide and dexamethasone with or without bortezomib: prospective evaluation of the impact of cytogenetic abnormalities and of previous therapies. Leukemia 24(10):1769–1778. doi:10.1038/leu.2010.175 PubMedCrossRef

32.

Reece D, Song KW, Fu T, Roland B, Chang H, Horsman DE, Mansoor A, Chen C, Masih-Khan E, Trieu Y, Bruyere H, Stewart DA, Bahlis NJ (2009) Influence of cytogenetics in patients with relapsed or refractory multiple myeloma treated with lenalidomide plus dexamethasone: adverse effect of deletion 17p13. Blood 114(3):522–525. doi:10.1182/blood-2008-12-193458 PubMedCrossRef

33.

Dimopoulos M, Alegre A, Stadtmauer EA, Goldschmidt H, Zonder JA, de Castro CM, Masliak Z, Reece D, Olesnyckyj M, Yu Z, Weber DM (2010) The efficacy and safety of lenalidomide plus dexamethasone in relapsed and/or refractory multiple myeloma patients with impaired renal function. Cancer 116(16):3807–3814. doi:10.1002/cncr.25139 PubMedCentralPubMedCrossRef

34.

Kleber M, Ihorst G, Udi J, Koch B, Wasch R, Engelhardt M (2012) Prognostic risk factor evaluation in patients with relapsed or refractory multiple myeloma receiving lenalidomide treatment: analysis of renal function by eGFR and of additional comorbidities by comorbidity appraisal. Clin Lymphoma Myeloma Leuk 12(1):38–48. doi:10.1016/j.clml.2011.09.216 PubMedCrossRef

35.

Oehrlein K, Langer C, Sturm I, Ponisch W, Hahn-Ast C, Kuhn S, Weisel KC (2012) Successful treatment of patients with multiple myeloma and impaired renal function with lenalidomide: results of 4 German Centers. Clin Lymphoma Myeloma Leuk 12(3):191–196. doi:10.1016/j.clml.2012.01.001 PubMedCrossRef

36.

Dimopoulos MA, Christoulas D, Roussou M, Kastritis E, Migkou M, Gavriatopoulou M, Matsouka C, Mparmparoussi D, Psimenou E, Grapsa I, Efstathiou E, Terpos E (2010) 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 85(1):1–5. doi:10.1111/j.1600-0609.2010.01432.x PubMed

37.

Dimopoulos MA, Richardson PG, Brandenburg N, Yu Z, Weber DM, Niesvizky R, Morgan GJ (2012) A review of second primary malignancy in patients with relapsed or refractory multiple myeloma treated with lenalidomide. Blood 119(12):2764–2767. doi:10.1182/blood-2011-08-373514 PubMedCrossRef

Title: Lenalidomide with dexamethasone treatment for relapsed/refractory myeloma patients in Korea—experience from 110 patients
Authors: Kihyun Kim
Seok Jin Kim
Verena Voelter
Cheolwon Suh
Sung-Soo Yoon
Je-Jung Lee
Jae-Yong Kwak
Hun-Mo Ryoo
Yang Soo Kim
Joon Ho Moon
Seong Kyu Park
Sung-Hyun Kim
Yeung-Chul Mun
Jin Seok Kim
Hyeon-Seok Eom
Deog-Yeon Jo
Hyun Jung Jun
Ki-Hwan Kim
Jeong-Ok Lee
Jae Hoon Lee
Chang-Ki Min
Korean Multiple Myeloma Working Party (KMMWP)
Publication date: 01-01-2014
Publisher: Springer Berlin Heidelberg
Published in: Annals of Hematology / Issue 1/2014
Print ISSN: 0939-5555
Electronic ISSN: 1432-0584
DOI: https://doi.org/10.1007/s00277-013-1893-z

ACC 2024 Congress Coverage

Heart Failure Video

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Lenalidomide with dexamethasone treatment for relapsed/refractory myeloma patients in Korea—experience from 110 patients

Abstract

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2014

MtDNA depletion and deletions may also have a role in myelodysplastic syndrome

Phase II trial to assess the safety and efficacy of clofarabine in combination with low-dose cytarabine in elderly patients with acute myeloid leukemia

The KIT D816V expressed allele burden for diagnosis and disease monitoring of systemic mastocytosis

“Real-world” data on the efficacy and safety of lenalidomide and dexamethasone in patients with relapsed/refractory multiple myeloma who were treated according to the standard clinical practice: a study of the Greek Myeloma Study Group

DCEP for relapsed or refractory multiple myeloma after therapy with novel agents

Prognostic impact of blast cell counts in dysplastic bone marrow disorders (MDS and CMML I) with concomitant fibrosis

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page