Real-World Bleeding Risk, Outcomes and Treatment Patterns of Patients with CLL/SLL Receiving BTKi with or without Prescription Anticoagulants or Antiplatelets

Introduction: Bruton tyrosine kinase inhibitors (BTKi) have transformed the treatment (tx) landscape of CLL/SLL. However, BTKi are associated with an increased risk of bleeding events that may complicate their use in patients (pts) with thrombotic disorders that require anticoagulant/antiplatelet (AC/AP) therapies. There is limited evidence about bleeding patterns in pts with concurrent BTKi and AC/AP use. This study aimed to evaluate BTKi and prescription (rx) AC/AP tx patterns, thrombotic outcomes, and healthcare resource utilization (HRU) after bleeding events in CLL/SLL pts using real-world US data.

Methods: A retrospective observational cohort study was conducted using the claims-linked Premier PINC AI Healthcare Database. Pts aged ≥18 years diagnosed with CLL/SLL between July 1, 2016 and March 31, 2022 with no BTKi exposure 3 months prior to index date (first rx fill date for BTKi) were included. Pts were followed from index date to earliest of BTKi discontinuation, death, or end of the study period (March 31, 2023). Rx claim data was used to capture BTKi and AC/AP use over time. Descriptive analysis was conducted to assess pt tx patterns (duration, discontinuation [>90-day gap], switches and gaps in BTKi and rx AC/AP) in overall and after first bleed. HRU was assessed after bleeding event and was described as post-bleed inpatient (inpt) and outpatient (outpt) care.

Results: Among the 2,091 CLL/SLL pts treated with BTKi (ibrutinib: 86.3%, acalabrutinib: 13.1% and zanubrutinib: <1%), mean (SD) age was 65.7 (11.3) years, 77.7% were white, 61.8% were male, and 23.0% had Charlson comorbidity index ≥5. Pts had mean 14.2 months of BTKi exposure and 29.4% were on concurrent rx AC/AP; 66.8% started after the index date. One quarter of the 526 (25.2%) bleeding events were gastrointestinal, 5.9% were intracranial and <0.3% were fatal. After the first bleeding event, 286 (54.4%) pts had a gap in BTKi tx for mean (min, max) 15 (1, 97) days, 13.3% discontinued BTKi, and <1.0% switched to another BTKi. At first bleed, 92 (17.5%) pts were on concurrent rx AC/AP tx; of whom 56.5% had a gap in AC/AP for a mean 34.2 (1, 90) days, 34.8% discontinued their AC/AP, and <2% discontinued all AC and AP. Of the 70 (13.3%) pts on rx AC with/out AP at first bleed, 61.4% had a gap in AC for a mean of 35.9 (1, 90) days and 31.4% discontinued their AC. Of the 27 (5.1%) pts on rx AP with/out AC at first bleed, 40.7% had a gap in rx AP for a mean of 23.9 (1, 56) days and 14.8% discontinued their AP tx. Among pts who experienced their first bleed, 23.3% of pts with rx AC/AP (n=103) vs.10.9% without AC/AP (n=423) during the study period had a subsequent thrombotic event ([stroke, TIA or VTE], p=.0009). The time to thrombotic event after a bleed for pts with rx AC/AP was a mean of 127 (8, 815) days vs. 203.1 (0, 1178) days for pts without rx AC/AP (p=0.1022). Pts on AC/AP underwent post-bleed inpt care for a mean (SD) of 3.8 (6.8) days and outpt care for 2.6 (3.4) days vs. no AC/AP for 2.0 (8.3; p<.0001) and 2.5 (3.6; p=0.942) days, respectively.

Conclusion: In this real-world study where one-third of BTKi-treated CLL/SLL pts received concurrent rx AC/AP, a quarter of all pts experienced a non-fatal bleed, resulting in <15% of the pts discontinuing and >50% pts interrupting their BTKi tx. More pts on rx AC (vs AP) discontinued or interrupted tx more often and for longer periods after first bleed. Although BTKi-treated pts with concurrent rx AC/AP experienced more post-bleeding thrombotic events and shorter time to post-bleed thrombosis, the latter did not reach statistical significance in this small subgroup. The mean inpt and outpt care post-bleeding event was <4 days, which may translate into a low economic burden for CLL/SLL pts on concurrent BTKi and AC/AP.