The risk of bleeding in patients receiving ibrutinib combined with novel direct oral anticoagulants

Abstract

the first to provide real-life data regarding the safety of administrating ibrutinib in combination with DOACs. While the combination of ibrutinib and DOACs is associated mainly with mild bleedings, the risk of major bleeding is not negligible. Further research with a larger sample size is important for refinement of additional risk factors for bleeding in patients treated with the combination of DOAC and ibrutinib, and will help determine the safety of concurrently employing these agents.In conclusion, concurrent administration of DOACs and ibrutinib appears to be acceptable. However, risk of bleeding is not negligible, and treatment resumption in patients that experienced a significant bleeding event should be considered with caution. Fig 2. (A) Left third mandibular molar teeth gingival ulcer. (B) Sigmoidoscopy showing the sigmoid colon lesion. (C) Whole body fludeoxyglucose positron emission tomography (FDG PETCT). Increased FDG uptake at the left mandibular gingival region. SUV 15.7, multifocal hypermetabolic activity in the sigmoid colon, maximum SUV 11.5. (D) FGD PETCT after two cycles of EBV CTLs. Resolution of the hypermetabolic activity of the left mandible and improved the diffused multifocal FDG uptake in the sigmoid colon.

Studies on platelet function during the first year of ibrutinib treatment in patients with chronic lymphocytic leukemia

“…According to Raz et al, when ibrutinib was used in combination with DOAC, most of the bleeding was grade 1-2, so the safety profile of concurrent treatment of DOAC and ibrutinib seemed tolerable [15]. In our patient receiving DOAC and ibrutinib simultaneously, we only observed minor (grade 1-2) bleeding events.…”

Characteristics and outcomes of patients on concurrent direct oral anticoagulants and targeted anticancer therapies—TacDOAC registry: Communication from the ISTH SSC Subcommittee on Hemostasis and Malignancy

“…32 More recently, a retrospective cohort study of 30 patients treated with ibrutinib and DOACs reported much higher bleeding rates: major bleeding events (grades 3 and 4) in 5 patients (16.6%) and overall bleeding events in 21 patients (73.3%) over a median follow-up of 13.4 months. 33 The newer generation BTK inhibitor, acalabrutinib, was designed to be more specific with presumably less off-target effects, but there were no data regarding its concurrent use with DOACs. In our study, we found a high rate of bleeding with concurrent use of BTK inhibitors and DOACs, with a 6-month incidence of major bleeding of 10% and that of non-major bleeding of 14%.…”

“…However, in these trials, the most commonly used concurrent anticoagulant was LMWH in prophylactic doses over a short duration (<3 months), with only four patients treated with DOACs 32 . More recently, a retrospective cohort study of 30 patients treated with ibrutinib and DOACs reported much higher bleeding rates: major bleeding events (grades 3 and 4) in 5 patients (16.6%) and overall bleeding events in 21 patients (73.3%) over a median follow‐up of 13.4 months 33 . The newer generation BTK inhibitor, acalabrutinib, was designed to be more specific with presumably less off‐target effects, but there were no data regarding its concurrent use with DOACs.…”

Risk of Bleeding Associated With Ibrutinib in Patients With B-Cell Malignancies: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

“…Studies are beginning to explore the safety of direct oral anticoagulants (DOACs) such as dabigatran, rivaroxaban, and apixaban in patients with ibrutinib. In a recent retrospective study, although the risk of bleeding was still high when ibrutinib was used in combination with DOACs, most of the bleeding was grade 1-2, so the safety profile of concurrent treatment of both DOACs and ibrutinib seemed tolerable (Raz et al, 2020). However, data were limited, and this study was a retrospective study with a small sample size, so more studies with larger sample size are needed to explore the safety of ibrutinib combined with DOACs.…”