Phase 1 trial of ibrutinib and carfilzomib combination therapy for relapsed or relapsed and refractory multiple myeloma. Leuk Lymphoma 2018 Nov;59(11):2588-2594
Date
04/05/2018Pubmed ID
29616843DOI
10.1080/10428194.2018.1443337Scopus ID
2-s2.0-85044964872 (requires institutional sign-in at Scopus site) 24 CitationsAbstract
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.
Author List
Chari A, Larson S, Holkova B, Cornell RF, Gasparetto C, Karanes C, Matous JV, Niesvizky R, Valent J, Lunning M, Usmani SZ, Anderson LD Jr, Chang L, Lee Y, Pak Y, Salman Z, Graef T, Bilotti E, Chhabra SMESH terms used to index this publication - Major topics in bold
AdenineAdult
Aged
Aged, 80 and over
Antineoplastic Combined Chemotherapy Protocols
Dexamethasone
Diarrhea
Disease-Free Survival
Dose-Response Relationship, Drug
Drug Resistance, Neoplasm
Fatigue
Female
Humans
Male
Middle Aged
Multiple Myeloma
Neoplasm Recurrence, Local
Oligopeptides
Piperidines
Pyrazoles
Pyrimidines
