Phase 1 trial of ibrutinib and carfilzomib combination therapy for relapsed or relapsed and refractory multiple myeloma

Ajai Chari, Sarah Larson, Beata Holkova, Robert F. Cornell, Cristina Gasparetto, Chatchada Karanes, Jeffrey V. Matous, Ruben Niesvizky, Jason Valent, Matthew Lunning, Saad Z. Usmani, Larry D. Anderson, Lipo Chang, Yihua Lee, Yvonne Pak, Zeena Salman, Thorsten Graef, Elizabeth Bilotti, Saurabh Chhabra

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

This phase 1, dose-finding study investigated ibrutinib and carfilzomib ± dexamethasone in patients with relapsed or relapsed/refractory multiple myeloma (≥2 lines of therapy including bortezomib and an immunomodulatory agent). Of 43 patients enrolled, 74% were refractory to bortezomib and 23% had high-risk cytogenetics. No dose-limiting toxicities were observed. The recommended phase 2 dose was ibrutinib 840 mg and carfilzomib 36 mg/m2 with dexamethasone. The most common ≥ grade 3 (>10%) treatment-emergent adverse events were hypertension, anemia, pneumonia, fatigue, diarrhea, and thrombocytopenia. Overall response rate was 67% (very good partial response, 21%; stringent complete response, 2%), with an additional 9% minimal response. Median progression-free survival was 7.2 months and was not inferior in refractory nor high-risk patients. Median overall survival was not reached. Ibrutinib plus carfilzomib demonstrated encouraging responses with a manageable safety profile in this advanced population.

Original languageEnglish (US)
Pages (from-to)2588-2594
Number of pages7
JournalLeukemia and Lymphoma
Volume59
Issue number11
DOIs
StatePublished - Nov 2 2018

Keywords

  • Bruton’s tyrosine kinase
  • Ibrutinib
  • carfilzomib
  • hematologic neoplasms
  • multiple myeloma

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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    Chari, A., Larson, S., Holkova, B., Cornell, R. F., Gasparetto, C., Karanes, C., Matous, J. V., Niesvizky, R., Valent, J., Lunning, M., Usmani, S. Z., Anderson, L. D., Chang, L., Lee, Y., Pak, Y., Salman, Z., Graef, T., Bilotti, E., & Chhabra, S. (2018). Phase 1 trial of ibrutinib and carfilzomib combination therapy for relapsed or relapsed and refractory multiple myeloma. Leukemia and Lymphoma, 59(11), 2588-2594. https://doi.org/10.1080/10428194.2018.1443337