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 A 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

6 Citations (Scopus)

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)1-7
Number of pages7
JournalLeukemia and Lymphoma
DOIs
StateAccepted/In press - Apr 5 2018

Fingerprint

Multiple Myeloma
Cytogenetics
Thrombocytopenia
Dexamethasone
Disease-Free Survival
Fatigue
Anemia
Diarrhea
Pneumonia
Therapeutics
Hypertension
Safety
Survival
Population
carfilzomib
PCI 32765
Bortezomib

Keywords

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

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Chari, A., Larson, S., Holkova, B., Cornell, R. F., Gasparetto, C., Karanes, C., ... Chhabra, S. (Accepted/In press). Phase 1 trial of ibrutinib and carfilzomib combination therapy for relapsed or relapsed and refractory multiple myeloma. Leukemia and Lymphoma, 1-7. https://doi.org/10.1080/10428194.2018.1443337

Phase 1 trial of ibrutinib and carfilzomib combination therapy for relapsed or relapsed and refractory multiple myeloma. / Chari, Ajai; Larson, Sarah; Holkova, Beata; Cornell, Robert F.; Gasparetto, Cristina; Karanes, Chatchada; Matous, Jeffrey V.; Niesvizky, Ruben; Valent, Jason; Lunning, Matthew A; Usmani, Saad Z.; Anderson, Larry D.; Chang, Lipo; Lee, Yihua; Pak, Yvonne; Salman, Zeena; Graef, Thorsten; Bilotti, Elizabeth; Chhabra, Saurabh.

In: Leukemia and Lymphoma, 05.04.2018, p. 1-7.

Research output: Contribution to journalArticle

Chari, A, Larson, S, Holkova, B, Cornell, RF, Gasparetto, C, Karanes, C, Matous, JV, Niesvizky, R, Valent, J, Lunning, MA, Usmani, SZ, Anderson, LD, 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, pp. 1-7. https://doi.org/10.1080/10428194.2018.1443337
Chari, Ajai ; Larson, Sarah ; Holkova, Beata ; Cornell, Robert F. ; Gasparetto, Cristina ; Karanes, Chatchada ; Matous, Jeffrey V. ; Niesvizky, Ruben ; Valent, Jason ; Lunning, Matthew A ; Usmani, Saad Z. ; Anderson, Larry D. ; Chang, Lipo ; Lee, Yihua ; Pak, Yvonne ; Salman, Zeena ; Graef, Thorsten ; Bilotti, Elizabeth ; Chhabra, Saurabh. / Phase 1 trial of ibrutinib and carfilzomib combination therapy for relapsed or relapsed and refractory multiple myeloma. In: Leukemia and Lymphoma. 2018 ; pp. 1-7.
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