Imbruvica (Ibrutinib) induced subcutaneous hematoma: A case report

Abstract Chronic Lymphocytic Leukemia (CLL) is one of the lymphoid neoplasms mainly affecting adults over age 55. Ibrutinib (Imbruvica) is currently the first-line therapy for various stages of CLL. It inhibits Bruton's Tyrosine Kinase (BTK). The most common adverse drug reactions include diarrhea, nausea, fatigue, rash, fever, and peripheral edema. Here, we report a case of subcutaneous hematoma in an 81-year-old male patient with CLL who was recently prescribed Imbruvica. At initial presentation, he had intermittently high WBC count (range: 15,000–16,000). Bone marrow biopsy showed low-grade B-cell lymphoproliferative disorder consistent with CLL. After 2 years into the diagnosis, leukocyte count began to rise, approaching 45,000 associated with worsening fatigue. Given the propensity of rapid progression and poor prognostic markers, Imbruvica was started. About two months into the therapy, he developed a reddish rash on both forearms and noticed increased bruising involving upper extremities consistent with ecchymoses. Imbruvica was stopped and later restarted at a lower dose of 140 mg daily. Leukocytosis responded well to the reduced dose. However, within a month, he again developed a rash on one of his forearm similar to the previous rash. Simultaneously, he developed redness and swelling of the left leg consistent with hematoma. INR was in therapeutic range (2.8) and the platelet count was 64,000/L (baseline range: 60,000/L–70,000/L). Review of system and physical examination were negative for a bleeding diathesis from any other organ system. Imbruvica was finally discontinued. His symptoms improved thereafter. Even though rare, Imbruvica induced hematoma is a serious adverse drug reaction. As per current guidelines, in case of major hemorrhage (Grade III-IV) the treatment should be stopped immediately. A frequent close follow up is recommended to ensure early recognition of progression of hematoma into a catastrophic pathology such as limb compartment syndrome. Alternate therapy like Acalabrutinib should be considered and the treatment-free period should be kept as short as possible especially in patients with aggressive disease course. Acalabrutinib also carries high risk of bleeding in such patients.