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A study of carfilzomib and dexamethasone in patients with relapsed and refractory multiple myeloma in China

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Abstract

The second-generation proteasome inhibitor carfilzomib produces superior outcomes in relapsed or refractory multiple myeloma (MM). We conducted a single-arm trial of twice-weekly carfilzomib (27 mg/m2)-dexamethasone (Kd27) for relapsed and refractory MM in China. Kd27 was administered in 28-day cycles to 123 patients previously treated with ≥ 2 other regimens, including treatment with bortezomib and an immunomodulatory drug, and refractory to their most recent therapy. Overall response rate (ORR) was the primary endpoint; progression-free survival (PFS) and overall survival (OS) were key secondary endpoints. Primary analysis was conducted when all patients received ≥ 6 cycles of Kd27 or discontinued Kd27. Median age was 60 years; median number of prior regimens was 4; 74% were refractory to proteasome inhibitors and immunomodulatory drugs. ORR was 35.8% (95% CI 27.3–44.9), median PFS was 5.6 (95% CI 4.6–6.5) months, and median OS was 16.6 (95% CI 12.2–NE) months. Grade ≥ 3 adverse events (AEs) occurred in 76.4% of patients. Grade ≥ 3 AEs of interest included hypertension (13.8%), acute renal failure (3.3%), cardiac failure (0.8%), ischemic heart disease (0.0%), and peripheral neuropathy (0.0%); 5.7% of patients discontinued carfilzomib due to AEs. Carfilzomib–dexamethasone produced a clinically meaningful response without new safety findings in Chinese patients with previously treated MM.

Trial registration: NCT03029234.

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References

  1. Landgren O, Iskander K. Modern multiple myeloma therapy: deep, sustained treatment response and good clinical outcomes. J Intern Med. 2017;281:365–82.

    Article  CAS  Google Scholar 

  2. Mateos MV, San Miguel JF. Management of multiple myeloma in the newly diagnosed patient. Hematol Am Soc Hematol Educ Progr. 2017;2017:498–507.

    Article  Google Scholar 

  3. Rollig C, Knop S, Bornhauser M. Multiple myeloma. Lancet. 2015;385:2197–208.

    Article  Google Scholar 

  4. Zhou M, Wang H, Zhu J, Chen W, Wang L, Liu S, et al. Cause-specific mortality for 240 causes in China during 1990–2013: a systematic subnational analysis for the Global Burden of Disease Study 2013. Lancet. 2016;387:251–72.

    Article  Google Scholar 

  5. Lu J, Lu J, Chen W, Huo Y, Huang X, Hou J. Clinical features and treatment outcome in newly diagnosed Chinese patients with multiple myeloma: results of a multicenter analysis. Blood Cancer J. 2014;4:e239.

    Article  CAS  Google Scholar 

  6. Hou J, Jin J, Xu Y, Wu D, Ke X, Zhou D, et al. Randomized, double-blind, placebo-controlled phase III study of ixazomib plus lenalidomide-dexamethasone in patients with relapsed/refractory multiple myeloma: China Continuation study. J Hematol Oncol. 2017;10:137.

    Article  Google Scholar 

  7. Kumar SK, Callander NS, Hillengass J, Liedtke M, Baljevic M, Campagnaro E, et al. NCCN guidelines insights: multiple myeloma, version 1.2020. J Natl Compr Cancer Netw JNCCN. 2019;17:1154–65.

    Article  Google Scholar 

  8. Chinese Hematology Association, Chinese Society of Hematology, Chinese Myeloma Committee-Chinese Hematology Association. The guidelines for the diagnosis and management of multiple myeloma in China (2020 revision). Zhonghua Nei Ke Za Zhi. 2020;2020(59):341–6.

    Google Scholar 

  9. Dimopoulos MA, Moreau P, Palumbo A, Joshua D, Pour L, Hajek R, et al. Carfilzomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma (ENDEAVOR): a randomised, phase 3, open-label, multicentre study. Lancet Oncol. 2016;17:27–38.

    Article  CAS  Google Scholar 

  10. Orlowski RZ, Moreau P, Niesvizky R, Ludwig H, Oriol A, Chng WJ, et al. Carfilzomib-dexamethasone versus bortezomib-dexamethasone in relapsed or refractory multiple myeloma: updated overall survival, safety, and subgroups. Clin Lymphoma Myeloma Leuk. 2019;19(522–30):e1.

    Google Scholar 

  11. Palumbo A, Chanan-Khan A, Weisel K, Nooka AK, Masszi T, Beksac M, et al. Daratumumab, bortezomib, and dexamethasone for multiple myeloma. N Engl J Med. 2016;375:754–66.

    Article  CAS  Google Scholar 

  12. Siegel DS, Dimopoulos MA, Ludwig H, Facon T, Goldschmidt H, Jakubowiak A, et al. Improvement in overall survival with carfilzomib, lenalidomide, and dexamethasone in patients with relapsed or refractory multiple myeloma. J Clin Oncol. 2018;36:728–34.

    Article  CAS  Google Scholar 

  13. Stewart AK, Rajkumar SV, Dimopoulos MA, Masszi T, Spicka I, Oriol A, et al. Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma. N Engl J Med. 2015;372:142–52.

    Article  Google Scholar 

  14. Hajek R, Masszi T, Petrucci MT, Palumbo A, Rosinol L, Nagler A, et al. A randomized phase III study of carfilzomib vs low-dose corticosteroids with optional cyclophosphamide in relapsed and refractory multiple myeloma (FOCUS). Leukemia. 2017;31:107–14.

    Article  CAS  Google Scholar 

  15. Miguel JS, Weisel K, Moreau P, Lacy M, Song K, Delforge M, et al. Pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone alone for patients with relapsed and refractory multiple myeloma (MM-003): a randomised, open-label, phase 3 trial. Lancet Oncol. 2013;14:1055–66.

    Article  CAS  Google Scholar 

  16. Richardson PG, Sonneveld P, Schuster MW, Irwin D, Stadtmauer EA, Facon T, et al. Bortezomib or high-dose dexamethasone for relapsed multiple myeloma. N Engl J Med. 2005;352:2487–98.

    Article  CAS  Google Scholar 

  17. Siegel DS, Martin T, Wang M, Vij R, Jakubowiak AJ, Lonial S, et al. A phase 2 study of single-agent carfilzomib (PX-171-003-A1) in patients with relapsed and refractory multiple myeloma. Blood. 2012;120:2817–25.

    Article  CAS  Google Scholar 

  18. Dimopoulos MA, Goldschmidt H, Niesvizky R, Joshua D, Chng WJ, Oriol A, et al. Carfilzomib or bortezomib in relapsed or refractory multiple myeloma (ENDEAVOR): an interim overall survival analysis of an open-label, randomised, phase 3 trial. Lancet Oncol. 2017;18:1327–37.

    Article  CAS  Google Scholar 

  19. Richardson PG, Barlogie B, Berenson J, Singhal S, Jagannath S, Irwin DH, et al. Extended follow-up of a phase II trial in relapsed, refractory multiple myeloma: final time-to-event results from the SUMMIT trial. Cancer. 2006;106:1316–9.

    Article  CAS  Google Scholar 

  20. Rajkumar SV, Jacobus S, Callander N, Fonseca R, Vesole D, Williams M, et al. A randomized trial of lenalidomide plus high-dose dexamethasone (RD) versus lenalidomide plus low-dose dexamethasone (Rd) in newly diagnosed multiple myeloma (E4A03): a trial coordinated by the Eastern Cooperative Oncology Group. Blood. 2007;110:74.

    Article  Google Scholar 

  21. Berenson JR, Cartmell A, Bessudo A, Lyons RM, Harb W, Tzachanis D, et al. CHAMPION-1: a phase 1/2 study of once-weekly carfilzomib and dexamethasone for relapsed or refractory multiple myeloma. Blood. 2016;127:3360–8.

    Article  CAS  Google Scholar 

  22. Moreau P, Mateos MV, Berenson JR, Weisel K, Lazzaro A, Song K, et al. Once weekly versus twice weekly carfilzomib dosing in patients with relapsed and refractory multiple myeloma (A.R.R.O.W.): interim analysis results of a randomised, phase 3 study. Lancet Oncol. 2018;19:953–64.

    Article  CAS  Google Scholar 

  23. Dimopoulos MA, Moreau P, Iida S, Huang SY, Takezako N, Chng WJ, et al. Outcomes for Asian patients with multiple myeloma receiving once- or twice-weekly carfilzomib-based therapy: a subgroup analysis of the randomized phase 3 ENDEAVOR and A.R.R.O.W. Trials. Int J Hematol. 2019;110:466–73.

    Article  CAS  Google Scholar 

  24. Ailawadhi S, Sexton R, Lentzsch S, Abidi MH, Voorhees PM, Cohen AD, et al. Low-dose versus high-dose carfilzomib with dexamethasone (S1304) in patients with relapsed-refractory multiple myeloma. Clin Cancer Res. 2020;26:3969–78.

    Article  CAS  Google Scholar 

  25. Moreau P, Masszi T, Grzasko N, Bahlis NJ, Hansson M, Pour L, et al. Oral ixazomib, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med. 2016;374:1621–34.

    Article  CAS  Google Scholar 

  26. Kim K, Lee JH, Kim JS, Min CK, Yoon SS, Shimizu K, et al. Clinical profiles of multiple myeloma in Asia-An Asian Myeloma Network study. Am J Hematol. 2014;89:751–6.

    Article  CAS  Google Scholar 

  27. Dimopoulos M, Quach H, Mateos MV, Landgren O, Leleu X, Siegel D, et al. Carfilzomib, dexamethasone, and daratumumab versus carfilzomib and dexamethasone for patients with relapsed or refractory multiple myeloma (CANDOR): results from a randomised, multicentre, open-label, phase 3 study. Lancet. 2020;396:186–97.

    Article  CAS  Google Scholar 

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Acknowledgements

Onyx Pharmaceuticals, Inc., an Amgen subsidiary, funded the study and was involved in study design; collection, analysis, and interpretation of data; and in the decision to submit this article for publication. We thank Yejiang Lou of Amgen China for providing valuable feedback during content development, and Yejiang Lou and Lin Shi of Amgen China for facilitating communication between the authors. Medical writing assistance was provided by Yin C. Lin of Amgen Inc., and funded by Amgen.

Funding

This study and the manuscript development were supported by Amgen Inc., Thousand Oaks, CA, USA.

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Authors and Affiliations

  1. Department of Hematology, Shanghai Changzheng Hospital, Shanghai, China

    Juan Du

  2. Department of Hematology, Henan Cancer Hospital, Zhengzhou, Henan, China

    Baijun Fang

  3. Department of Hematology, Peking Union Medical College Hospital, Beijing, China

    Jian Li

  4. Department of Hematology, The First Affiliated Hospital, Zhejiang University College of Medicine, Hangzhou, Zhejiang, China

    Jie Jin & Zhen Cai

  5. Department of Hematology, Guangzhou First People’s Hospital, Guangzhou, Guangdong, China

    Shunqing Wang

  6. Department of Lymphoma and Myeloma, Institute of Hematology and Hospital of Blood Disease, Tianjin, China

    Dehui Zou

  7. Department of Hematology, Central Hospital of Wuhan, Wuhan, Hubei, China

    Hongxiang Wang

  8. Department of Hematology, Fujian Medical University Union Hospital, Fuzhou, Fujian, China

    Jianda Hu

  9. Department of Hematology, The First Hospital of Jilin University, Changchun , Jilin, China

    Wei Li

  10. Department of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China

    Chengcheng Fu

  11. Department of Hematology and Oncology, Tianjin Medical University General Hospital, Tianjin, China

    Zonghong Shao

  12. Department of Hematology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China

    Zhongjun Xia

  13. Department of Hematology, Zhongshan Hospital Fudan University, Shanghai, China

    Peng Liu

  14. Department of Hematology, West China Hospital, Sichuan University, Chengdu, Sichuan, China

    Ting Niu

  15. Global Biometric Data Science, Amgen Inc., Shanghai, China

    En-Tzu Tang

  16. Global Development, Amgen Inc, Thousand Oaks, CA, USA

    Amy S. Kimball

  17. Department of Hematology, Shanghai Renji Hospital, 160 Pujian Road, Pudong New District, Shanghai, China

    Jian Hou

  18. Department of Hematology, Beijing Chao Yang Hospital, Capital Medical University, 8 Gongti South Road, Beijing, 100020, China

    Wenming Chen

Authors
  1. Juan Du
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  2. Baijun Fang
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  3. Jian Li
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  4. Jie Jin
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  10. Wei Li
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  14. Peng Liu
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  15. Ting Niu
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  16. En-Tzu Tang
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  18. Jian Hou
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  19. Wenming Chen
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Corresponding authors

Correspondence to Jian Hou or Wenming Chen.

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Conflict of interest

JD, BF, JL, JJ, SW, DZ, ZC, HW, Jianda H, WL, CF, ZS, ZX, PL, TN, Jian H, and WC declare no conflicts of interest. E-TT reports employment with Amgen and stock holdings from Amgen. ASK reports employment with Amgen and stock holdings from Amgen and WindMIL.

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Du, J., Fang, B., Li, J. et al. A study of carfilzomib and dexamethasone in patients with relapsed and refractory multiple myeloma in China. Int J Hematol 113, 422–429 (2021). https://doi.org/10.1007/s12185-020-03044-z

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  • DOI: https://doi.org/10.1007/s12185-020-03044-z

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