Final analysis of a phase 1/2b study of ibrutinib combined with carfilzomib/dexamethasone in patients with relapsed/refractory multiple myeloma.

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  • Additional Information
    • Affiliation:
      Department of Hematology and Medical Oncology, Mount Sinai School of Medicine, New York New York
      Division of Hematology and Oncology, Vanderbilt University Medical Center, Nashville Tennessee
      Division of Hematologic Malignancies and Cellular Therapy, Duke University Health System, Durham North Carolina
      Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte California
      Department of Hematology/Oncology, Colorado Blood Cancer Institute, Denver Colorado
      Department of Medical Oncology, Weill Cornell Medicine, New York New York
      Division of Oncology & Hematology, University of Nebraska Medical Center, Omaha Nebraska
      Department of Hematologic Oncology & Blood Disorders, Levine Cancer Institute, Atrium Health, Charlotte North Carolina
      Division of Hematology Oncology, Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas Texas
      Division of Hematology/Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee Wisconsin
      Department of Medicine, University of Cincinnati Cancer Institute, Cincinnati Ohio
      Division of Hematology, Cedars Cancer Centre, McGill University Health Centre, Montreal Quebec,, Canada
      Division of Hematology/Oncology, Medical University of South Carolina, Charleston South Carolina
      Pharmacyclics LLC, an AbbVie Company, Sunnyvale California
      Department of Hematology and Medical Oncology, Cleveland Clinic Foundation, Cleveland Ohio
      Division of Hematology Oncology, Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, Texas
    • Subject Terms:
    • Subject Terms:
    • Abstract:
      Patients with multiple myeloma (MM) inevitably relapse on initial treatment regimens, and novel combination therapies are needed. Ibrutinib is a first-in-class, once-daily inhibitor of Bruton's tyrosine kinase, an enzyme implicated in growth and survival of MM cells. Preclinical data suggest supra-additivity or synergy between ibrutinib and proteasome inhibitors (PIs) against MM. This phase 1/2b study evaluated the efficacy and safety of ibrutinib plus the PI carfilzomib and dexamethasone in patients with relapsed/refractory MM (RRMM). In this final analysis, we report results in patients who received the recommended phase 2 dose (RP2D; ibrutinib 840 mg and carfilzomib 36 mg/m2 with dexamethasone), which was determined in phase 1. The primary efficacy endpoint was overall response rate (ORR). Fifty-nine patients with RRMM received the RP2D (18 in phase 1 and 41 in phase 2b). These patients had received a median of three prior lines of therapy; 69% were refractory to bortezomib, and 90% were refractory to their last treatment. ORR in the RP2D population was 71% (stringent complete response and complete response: 3% each). Median duration of clinical benefit and median duration of response were both 6.5 months. Median progression-free survival (PFS) was 7.4 months, and median overall survival (OS) was 35.9 months. High-risk patients had comparable ORR and median PFS (67% and 7.7 months, respectively) to non-high-risk patients, whose ORR was 73% and median PFS was 6.9 months, whereas median OS in high-risk patients was 13.9 months and not reached in non-high-risk patients. The most common grade ≥3 hematologic treatment-emergent adverse events (TEAEs) were anemia and thrombocytopenia (17% each); the most common grade ≥3 non-hematologic TEAE was hypertension (19%). In patients with RRMM treated with multiple previous lines of therapy, ibrutinib plus carfilzomib demonstrated anticancer activity within the expected efficacy range. No new safety signals were identified and the combination was well-tolerated.
    • Journal Subset:
      Biomedical; Europe; Peer Reviewed; UK & Ireland
    • Special Interest:
      Evidence-Based Practice
    • Instrumentation:
      Piper Fatigue Scale (PFS)
      Clinical Decision Making in Nursing Scale (CDMNS) (Jenkins)
      Plaque Index (PI)
    • ISSN:
      0278-0232
    • MEDLINE Info:
      PMID: NLM32053229 NLM UID: 8307268
    • Grant Information:
      No grant or award number//Pharmacyclics LLC, an AbbVie Company/
    • Publication Date:
      In Process
    • Publication Date:
      20201002
    • DOI:
      10.1002/hon.2723
    • Accession Number:
      145206032
  • Citations
    • ABNT:
      CHARI, A. et al. Final analysis of a phase 1/2b study of ibrutinib combined with carfilzomib/dexamethasone in patients with relapsed/refractory multiple myeloma. Hematological Oncology, [s. l.], v. 38, n. 3, p. 353–362, 2020. DOI 10.1002/hon.2723. Disponível em: http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=rzh&AN=145206032. Acesso em: 26 nov. 2020.
    • AMA:
      Chari A, Cornell RF, Gasparetto C, et al. Final analysis of a phase 1/2b study of ibrutinib combined with carfilzomib/dexamethasone in patients with relapsed/refractory multiple myeloma. Hematological Oncology. 2020;38(3):353-362. doi:10.1002/hon.2723
    • APA:
      Chari, A., Cornell, R. F., Gasparetto, C., Karanes, C., Matous, J. V., Niesvizky, R., Lunning, M., Usmani, S. Z., Anderson, L. D., Chhabra, S., Girnius, S., Shustik, C., Stuart, R., Lee, Y., Salman, Z., Liu, E., Valent, J., & Anderson, L. D., Jr. (2020). Final analysis of a phase 1/2b study of ibrutinib combined with carfilzomib/dexamethasone in patients with relapsed/refractory multiple myeloma. Hematological Oncology, 38(3), 353–362. https://doi.org/10.1002/hon.2723
    • Chicago/Turabian: Author-Date:
      Chari, Ajai, Robert F. Cornell, Cristina Gasparetto, Chatchada Karanes, Jeffrey V. Matous, Ruben Niesvizky, Matthew Lunning, et al. 2020. “Final Analysis of a Phase 1/2b Study of Ibrutinib Combined with Carfilzomib/Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma.” Hematological Oncology 38 (3): 353–62. doi:10.1002/hon.2723.
    • Harvard:
      Chari, A. et al. (2020) ‘Final analysis of a phase 1/2b study of ibrutinib combined with carfilzomib/dexamethasone in patients with relapsed/refractory multiple myeloma’, Hematological Oncology, 38(3), pp. 353–362. doi: 10.1002/hon.2723.
    • Harvard: Australian:
      Chari, A, Cornell, RF, Gasparetto, C, Karanes, C, Matous, JV, Niesvizky, R, Lunning, M, Usmani, SZ, Anderson, LD, Chhabra, S, Girnius, S, Shustik, C, Stuart, R, Lee, Y, Salman, Z, Liu, E, Valent, J & Anderson, LD, Jr 2020, ‘Final analysis of a phase 1/2b study of ibrutinib combined with carfilzomib/dexamethasone in patients with relapsed/refractory multiple myeloma’, Hematological Oncology, vol. 38, no. 3, pp. 353–362, viewed 26 November 2020, .
    • MLA:
      Chari, Ajai, et al. “Final Analysis of a Phase 1/2b Study of Ibrutinib Combined with Carfilzomib/Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma.” Hematological Oncology, vol. 38, no. 3, Aug. 2020, pp. 353–362. EBSCOhost, doi:10.1002/hon.2723.
    • Chicago/Turabian: Humanities:
      Chari, Ajai, Robert F. Cornell, Cristina Gasparetto, Chatchada Karanes, Jeffrey V. Matous, Ruben Niesvizky, Matthew Lunning, et al. “Final Analysis of a Phase 1/2b Study of Ibrutinib Combined with Carfilzomib/Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma.” Hematological Oncology 38, no. 3 (August 2020): 353–62. doi:10.1002/hon.2723.
    • Vancouver/ICMJE:
      Chari A, Cornell RF, Gasparetto C, Karanes C, Matous JV, Niesvizky R, et al. Final analysis of a phase 1/2b study of ibrutinib combined with carfilzomib/dexamethasone in patients with relapsed/refractory multiple myeloma. Hematological Oncology [Internet]. 2020 Aug [cited 2020 Nov 26];38(3):353–62. Available from: http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=rzh&AN=145206032