A phase 2 study of ibrutinib in combination with bortezomib and dexamethasone in patients with relapsed/refractory multiple myeloma

Abstract

Objective:We evaluated ibrutinib, a once-daily inhibitor of Bruton's tyrosine kinase, combined with bortezomib and dexamethasone in patients with relapsed or relapsed/ refractory multiple myeloma who had received 1-3 prior therapies. Methods:This was a phase 2, single-arm, open-label, multicentre study (NCT02902965).The primary endpoint was progression-free survival (PFS). Results:Seventy-six patients were enrolled; 74 received ≥1 dose of study treatment. After median follow-up of 19.6 months, median PFS was 8.5 months (95% CI: 6.2-10.8); median overall survival was not reached. Overall response rate was 57% (95% CI: 45-68), and median duration of response was 9.5 months (95% CI: 6.9-10.6).Grade 3/4 AEs occurred in 73% of patients and fatal AEs occurred in 15% of patients.Incidence of major haemorrhage was 5%; one patient died from cerebral haemorrhage. After an observed increased incidence of serious (42%) and fatal (11%) infections, enrolment was suspended to implement risk-minimisation measures. The safety profile was otherwise consistent with known safety profiles of the individual drugs. Conclusion: Ibrutinib combined with bortezomib and dexamethasone elicited clinicalresponses. However, efficacy assessments conducted at potential restart of enrolment indicated that the targeted PFS could not be reached with additional patient enrolment, and the study was terminated. K E Y W O R D S bortezomib, dexamethasone, ibrutinib, multiple myelomaThis is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Systematic review of infectious events with the Bruton tyrosine kinase inhibitor ibrutinib in the treatment of hematologic malignancies

“…Infectious complications were reported in 92% (44/48) of trials with sufficient data for the final analysis. Table and Table summarize findings for those studies investigating ibrutinib as a single agent, or in combination with one or more other antineoplastics, respectively. One single‐agent trial and 3 combination studies included in the final infectious AE data had no reported infectious complications.…”

Bruton’s Tyrosine Kinase Targeting in Multiple Myeloma

“…Nevertheless, 57% of patients had clinical responses with a median response duration of 9.5 months. The study was ultimately terminated due to an inability to achieve the primary endpoint [ 67 ].…”

Drug Review: Ibrutinib

“…[74] Ibrutinib has failed to show any major benefit in relapsed myeloma and follicular lymphoma. [75,76] The drug modulates the tumor microenvironment and hence, it has been tried with some success in varied nonhematological malignancies including gynecological malignancies, pancreatic carcinoma, prostate cancer, and glioblastoma multiforme. [77][78][79][80]…”