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

Journal Article (Journal Article;Multicenter Study)

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.

Full Text

Duke Authors

Cited Authors

  • Chari, A; Larson, S; Holkova, B; Cornell, RF; Gasparetto, C; Karanes, C; Matous, JV; Niesvizky, R; Valent, J; Lunning, M; Usmani, SZ; Anderson, LD; Chang, L; Lee, Y; Pak, Y; Salman, Z; Graef, T; Bilotti, E; Chhabra, S

Published Date

  • November 2018

Published In

Volume / Issue

  • 59 / 11

Start / End Page

  • 2588 - 2594

PubMed ID

  • 29616843

Electronic International Standard Serial Number (EISSN)

  • 1029-2403

Digital Object Identifier (DOI)

  • 10.1080/10428194.2018.1443337


  • eng

Conference Location

  • United States