Ibrutinib-Associated Life-Threatening Hemorrhage with Subcapsular Renal Hematoma and Hemothorax

Background: Ibrutinib is an irreversible inhibitor of Bruton tyrosine kinase (BTK) which is FDA approved for treatment of chronic lymphocytic leukemia (CLL) and multiple other B-cell lymphoproliferative disorders. Ibrutinib therapy is associated with increased risk of bleeding. We report an unusual but life-threatening case of hemorrhage with subcapsular renal hematoma and large hemothorax secondary to Ibrutinib. Case Presentation: An 85-year-old male with history of CLL started on a reduced dose of ibrutinib presented with acute onset left sided flank Archives of Clinical and Medical Case Reports and acute kidney failure. Imaging revealed moderate to large left sided pleural effusion and a renal mass concerning for renal neoplasm. He underwent thoracentesis revealing hemothorax. The patient was managed conservatively with intravenous hydration for his acute renal failure, blood transfusions and pain medications. His pain resolved; blood counts eventually stabilized and he was discharged from the hospital. The renal mass was later diagnosed as a large subcapsular renal hematoma after further review by another radiologist who determined that the Hounsfield unit of the mass was consistent with blood. Conclusions: This case illustrates a case of life-threatening hemorrhage that required hospitalization after 2 weeks of initiation of ibrutinib. Hemorrhage can occur despite reduced dose, and can result in hemorrhagic pleural effusion and bleeding in solid organs like the kidney. The presence of sudden large masses in a solid organ in a patient on ibrutinib should elicit the differential of intra-organ hemorrhage. Initiation of ibrutinib should be done cautiously, especially in elderly patients.

[1]  A. Mato,et al.  Zanubrutinib (BGB-3111), a Second-Generation Selective Covalent Inhibitor of Bruton’s Tyrosine Kinase and Its Utility in Treating Chronic Lymphocytic Leukemia , 2021, Drug design, development and therapy.

[2]  F. J. López-Jiménez,et al.  Intracranial hemorrhage as presentation of chronic lymphocytic leukemia successfully treated with ibrutinib , 2021, Annals of Hematology.

[3]  B. Payrastre,et al.  Effects of novel Btk and Syk inhibitors on platelet functions alone and in combination in vitro and in vivo , 2020, Journal of thrombosis and haemostasis : JTH.

[4]  M. Dimopoulos,et al.  A RANDOMIZED PHASE 3 TRIAL OF ZANUBRUTINIB VERSUS IBRUTINIB IN SYMPTOMATIC WALDENSTRÖM MACROGLOBULINEMIA:THE ASPEN STUDY. , 2020, Blood.

[5]  F. Lansigan,et al.  Diffuse Alveolar Hemorrhage Secondary to Ibrutinib Therapy in a Patient With Refractory Mantle Cell Lymphoma , 2020, Cureus.

[6]  R. Condos,et al.  Spontaneous Hemothorax in a Patient on Ibrutinib , 2020 .

[7]  C. Bennett,et al.  Major hemorrhage in chronic lymphocytic leukemia patients in the US Veterans Health Administration system in the pre‐ibrutinib era: Incidence and risk factors , 2019, Cancer medicine.

[8]  S. Treon,et al.  Ibrutinib Monotherapy in Symptomatic, Treatment-Naïve Patients With Waldenström Macroglobulinemia. , 2018, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[9]  R. Hendriks,et al.  Role of Bruton’s tyrosine kinase in B cells and malignancies , 2018, Molecular Cancer.

[10]  D. Leong,et al.  Current understanding of bleeding with ibrutinib use: a systematic review and meta-analysis. , 2017, Blood advances.

[11]  C. Flowers,et al.  Targeting Bruton tyrosine kinase with ibrutinib in relapsed/refractory marginal zone lymphoma. , 2017, Blood.

[12]  P. Prandoni,et al.  Increased dabigatran plasma concentration during Ibrutinib treatment: a case of cerebral hemorrhage and successful dabigatran reversal by idarucizumab , 2017, Aging Clinical and Experimental Research.

[13]  A. Saven,et al.  Spontaneous Iliopsoas Muscle Hemorrhage Secondary to Ibrutinib (Imbruvica; Pharmacyclics) , 2016, Journal of investigative medicine high impact case reports.

[14]  Mingzhi Zhang,et al.  Acalabrutinib (ACP-196): a selective second-generation BTK inhibitor , 2016, Journal of Hematology & Oncology.

[15]  Nibedita Bandyopadhyay,et al.  Ibrutinib versus temsirolimus in patients with relapsed or refractory mantle-cell lymphoma: an international, randomised, open-label, phase 3 study , 2016, The Lancet.

[16]  M. Hallek,et al.  Ibrutinib combined with bendamustine and rituximab compared with placebo, bendamustine, and rituximab for previously treated chronic lymphocytic leukaemia or small lymphocytic lymphoma (HELIOS): a randomised, double-blind, phase 3 study. , 2016, The Lancet. Oncology.

[17]  T. Kipps,et al.  Ibrutinib as Initial Therapy for Patients with Chronic Lymphocytic Leukemia. , 2015, The New England journal of medicine.