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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

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Abstract

Carfilzomib is an irreversible proteasome inhibitor used for the treatment of relapsed and/or refractory multiple myeloma (RRMM). We evaluated the efficacy and safety of carfilzomib in subgroups of Asian patients in the randomized phase 3 ENDEAVOR and A.R.R.O.W. trials. In ENDEAVOR, patients received carfilzomib twice-weekly (56 mg/m2) plus dexamethasone (Kd; n = 56) or bortezomib plus dexamethasone (Vd; n = 57). In A.R.R.O.W., patients received carfilzomib once-weekly (70 mg/m2, n = 30) or twice-weekly (27 mg/m2, n = 15) plus dexamethasone. Median progression-free survival (PFS) among Asian patients in ENDEAVOR was longer with Kd than with Vd (14.9 versus 8.8 months; HR 0.599); the overall response rate (ORR) was 80.4% versus 70.2%. Median overall survival (Kd versus Vd) was 47.6 versus 38.8 months (HR 0.856). Median PFS among Asian patients in A.R.R.O.W. was longer for once-weekly versus twice-weekly Kd (16.0 versus 8.4 months; HR 0.628); ORR was 76.7% versus 53.3%. Rates of grade ≥ 3 adverse events were 89.1% (Kd) and 89.5% (Vd) in ENDEAVOR, and 76.6% (once-weekly Kd) versus 73.3% (twice-weekly Kd) in A.R.R.O.W. Overall, carfilzomib had a favorable benefit-risk profile across both dosing regimens [once-weekly (Kd 70 mg/m2) and twice-weekly (Kd 56 mg/m2)] in Asian patients with RRMM, which was consistent with the results of both parent studies.

Trial registration ClinicalTrials.gov: NCT01568866, NCT02412878.

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References

  1. Cowan AJ, Allen C, Barac A, Basaleem H, Bensenor I, Curado MP, et al. Global burden of multiple myeloma: a systematic analysis for the Global Burden of Disease study 2016. JAMA Oncol. 2018;4:1221–7.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Cornell RF, Kassim AA. Evolving paradigms in the treatment of relapsed/refractory multiple myeloma: increased options and increased complexity. Bone Marrow Transpl. 2016;51:479–91.

    Article  CAS  Google Scholar 

  3. 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  PubMed  Google Scholar 

  4. Hong J, Lee JH. Recent advances in multiple myeloma: a Korean perspective. Korean J Intern Med. 2016;31:820–34.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Kumar SK, Dispenzieri A, Lacy MQ, Gertz MA, Buadi FK, Pandey S, et al. Continued improvement in survival in multiple myeloma: changes in early mortality and outcomes in older patients. Leukemia. 2014;28:1122–8.

    Article  CAS  PubMed  Google Scholar 

  6. Tan D, Lee JH, Chen W, Shimizu K, Hou J, Suzuki K, et al. Recent advances in the management of multiple myeloma: clinical impact based on resource-stratification. Consensus statement of the Asian Myeloma Network at the 16th International Myeloma Workshop. Leuk Lymphoma. 2018;59:1–13.

    Article  Google Scholar 

  7. Suzuki K, Dimopoulos MA, Takezako N, Okamoto S, Shinagawa A, Matsumoto M, et al. Daratumumab, lenalidomide, and dexamethasone in East Asian patients with relapsed or refractory multiple myeloma: subgroup analyses of the phase 3 POLLUX study. Blood Cancer J. 2018;8:41.

    Article  PubMed  PubMed Central  Google Scholar 

  8. 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  CAS  PubMed  PubMed Central  Google Scholar 

  9. Dimopoulos MA, Oriol A, Nahi H, San-Miguel J, Bahlis NJ, Usmani SZ, et al. Daratumumab, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med. 2016;375:1319–31.

    Article  CAS  PubMed  Google Scholar 

  10. 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  PubMed  Google Scholar 

  11. Kyprolis® (carfilzomib). Full prescribing information. Thousand Oaks: Amgen Inc.; 2018.

    Google Scholar 

  12. Kyprolis (carfilzomib). Summary of product characteristics. Breda: Amgen Europe; 2018.

    Google Scholar 

  13. 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 

  14. 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  PubMed  Google Scholar 

  15. 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  PubMed  Google Scholar 

  16. Mikhael J. Management of carfilzomib-associated cardiac adverse events. Clin Lymphoma Myeloma Leuk. 2016;16:241–5.

    Article  PubMed  Google Scholar 

  17. Watanabe T, Tobinai K, Matsumoto M, Suzuki K, Sunami K, Ishida T, et al. A phase 1/2 study of carfilzomib in Japanese patients with relapsed and/or refractory multiple myeloma. Br J Haematol. 2016;172:745–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Iida S, Tobinai K, Taniwaki M, Shumiya Y, Nakamura T, Chou T. Phase I dose escalation study of high dose carfilzomib monotherapy for Japanese patients with relapsed or refractory multiple myeloma. Int J Hematol. 2016;104:596–604.

    Article  CAS  PubMed  Google Scholar 

  19. Maruyama D, Tobinai K, Chou T, Taniwaki M, Shumiya Y, Iida S. Weekly carfilzomib and dexamethasone in Japanese patients with relapsed or refractory multiple myeloma: a phase 1 and PK/PD trial. Cancer Sci. 2018;109:3245–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Suzuki K, Ri M, Chou T, Sugiura I, Takezako N, Sunami K, et al. Carfilzomib, lenalidomide and dexamethasone in patients with heavily pretreated multiple myeloma: a phase 1 study in Japan. Cancer Sci. 2017;108:461–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. 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  CAS  PubMed  Google Scholar 

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Acknowledgements

The authors thank the patients and sites for their participation in the ENDEAVOR and A.R.R.O.W. trials. Jesse Potash, PhD (Amgen Inc.) and Meghan Johnson, PhD (Complete Healthcare Communications, LLC, an ICON plc company, North Wales, PA, USA), whose work was funded by Amgen Inc., provided medical writing assistance in the preparation of this manuscript.

Funding

The ENDEAVOR and A.R.R.O.W. studies were sponsored and funded by Amgen Inc.

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Authors and Affiliations

  1. Department of Clinical Therapeutics, National and Kapodistrian University of Athens, Alexandra Hospital, 80 Vas Sofias Avenue, 11528, Athens, Greece

    Meletios A. Dimopoulos

  2. University of Nantes, Nantes, France

    Philippe Moreau

  3. Nagoya City University Hospital, Nagoya, Japan

    Shinsuke Iida

  4. National Taiwan University Hospital, Taipei City, Taiwan

    Shang-Yi Huang

  5. National Hospital Organization Disaster Medical Center of Japan, Tachikawa, Japan

    Naoki Takezako

  6. National University Cancer Institute, National University Health System, Singapore, Singapore

    Wee Joo Chng

  7. Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore

    Wee Joo Chng

  8. Amgen Inc., Thousand Oaks, CA, USA

    Anita Zahlten-Kumeli, Martina A. Sersch, Julia Li & Mei Huang

  9. Gil Medical Center, Gachon University College of Medicine, Incheon, South Korea

    Jae Hoon Lee

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  1. Meletios A. Dimopoulos
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  2. Philippe Moreau
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  9. Julia Li
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Correspondence to Meletios A. Dimopoulos.

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Conflict of interest

MAD reports receiving honoraria and consulting and/or advisory role fees from Celgene, Janssen, Amgen Inc., Novartis, and Takeda, and research funding from Genesis Pharma. PM reports receiving honoraria from and advisory board participation with Amgen Inc., Celgene, Takeda, Janssen, and AbbVie. SI reports receiving research grants and consulting fees from Ono Pharmaceutical Co., Ltd., Janssen, Celgene, Takeda, Bristol-Myers Squibb, and Novartis; and research grants from Chugai, Teijin Pharma, Astellas, Toyama Chemical, Eli Lilly, Kyowa Hakko Kirin, Sanofi, AbbVie, Merck Sharp & Dohme, and Daiichi Sanko. WJC reports receiving research grants from Celgene, Janssen, Novartis, Takeda, and Amgen Inc.; and consulting fees from Celgene, Janssen, Novartis, Takeda, and Amgen Inc. AZ-K, MAS, JL, and MH are employees of and own stock in Amgen Inc. S-YH, NT, and JHL have nothing to disclose.

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Dimopoulos, M.A., Moreau, P., Iida, S. 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 110, 466–473 (2019). https://doi.org/10.1007/s12185-019-02704-z

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  • DOI: https://doi.org/10.1007/s12185-019-02704-z

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