PF385 ANTICOAGULATION IN PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA (CLL) TREATED WITH IBRUTINIB
Authors: W.J. Archibald, W. Ding, T.G. Call, K.G. Rabe, A.B. Koehler, N.E. Kay, S.S. Kenderian, J.F. Leis, B.F. Kabat, S.M. Schwager, A.L. Fonder, S.L. Slager, E. Muchtar, S.A. Parikh
Journal: HemaSphere (2019)

Background: Ibrutinib therapy is associated with an increased risk of bleeding due to a currently poorly understood effect on multiple platelet signaling pathways, with up to 35% of patients experiencing bleeding events on ibrutinib therapy (Brown; Br J Hem 2019). The optimal anticoagulation strategy is unknown when a patient receiving ibrutinib therapy has an indication for anticoagulation. Aims: To describe Mayo Clinic's experience with anticoagulation therapy among patients with CLL treated with ibrutinib. Methods: An IRB approved retrospective chart review of patients with CLL treated with ibrutinib at Mayo Clinic between 30 Oct 2012 and 1 Nov 2018. Results: 299 CLL patients were identified with a total of 565 years of ibrutinib exposure and a median follow up of 24 months (range 0–70 months) (Table 1). At the time of ibrutinib initiation, 20 patients (6.4%) were already on anticoagulation (12 apixaban, 5 enoxaparin, 2 rivaroxaban, 1 warfarin). Reasons for anticoagulation included stroke prophylaxis due to atrial fibrillation in 8 (40%) pts, history of venous thromboembolism (VTE) in 10 (50%) pts (PE in 7 pts, DVT in 3 pts), and presence of a mechanical heart valve in 2 (10%) pts. Two of these patients were on concomitant antiplatelet agents. The starting dose of ibrutinib was reduced to due to concomitant anticoagulation in 8 patients. During the course of ibrutinib therapy, an additional 17 pts initiated anticoagulation (11 apixaban, 4 rivaroxaban, 1 dabigatran, 1 enoxaparin). Reasons for anticoagulation included stroke prophylaxis due to treatment emergent atrial fibrillation in 15 (88.2%) pts and VTE (pulmonary embolism) in 2 (11.8%) pts. Eight of these patients were on concomitant antiplatelet agents in addition to anticoagulation. The 6-month and 1-year risk of treatment-emergent indication for anticoagulation was 4% (95%CI: 1–6%) and 5% (95%CI: 2–8%), respectively. Of all patients treated with anticoagulation while on ibrutinib (n = 37), 16 patients (43%) developed clinically relevant bleeding (3 major, and 13 minor bleeding). Of three patients with major bleeding events, one had a life threatening gastrointestinal (GI) bleed on apixaban (ibrutinib was held for 5 days and was restarted at 140 mg daily and apixaban was held for one week), one patient had fatal hemorrhagic bilateral pleural effusion while on warfarin therapy with a supratherapeutic INR (ibrutinib was dose reduced to once every 3 days, and warfarin was discontinued and not restarted prior to the patient expiring) and one patient had a spontaneous subdural hematoma while on concomitant rivaroxaban and aspirin therapy (ibrutinib, anticoagulation, and antiplatelet agents were discontinued permanently). In the 13 patients with minor bleeding events, the site of bleeding was: 6 genitourinary, 4 skin, 1 soft tissue, 1 tympanic, and 1 GI. Anticoagulation was discontinued permanently in 7 pts, continued at the same dose in 5 pts, and held for one month in 1 pt. Ibrutinib was discontinued permanently in 1 pt, continued at the same dose in 8 pts, held temporarily in 2 pts, and dose reduced in 2 pts. Anticoagulation therapy was effective for patients who received it given that no patient experienced a thrombotic stroke or subsequent venous thromboembolism while on anticoagulation therapy.Summary/Conclusion: Anticoagulation in patients with CLL treated with ibrutinib can be effective and relatively well tolerated, however, significant bleeding can occur and patients need to be closely monitored. Ibrutinib should be managed carefully in patients who develop bleeding complications.