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 first-line therapy for various stages of CLL. It inhibits Bruton's Tyrosine Kinase (BTK). Its 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 started with Imbruvica after he showed progression of his disease. On his initial presentation, he had intermittently high WBC count (range 15000-16,000). 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 and he began to feel more fatigued. Given the propensity of rapid progression and poor prognostic markers, he was started on imbruvica. About two months into Imbruvica therapy, he developed a reddish rash on both his forearms and noticed increased bruising in his upper extremities which were consistent with ecchymoses. His Imbruvica was stopped and later restarted at a lower dose of 140mg daily. Leukocytosis responded well to the reduced dose. However, within a month, he again started to develop a rash in his forearm similar to before. Simultaneously, he also developed redness and swelling in his left leg consistent with hematoma. At that time his INR was 2.8 and his Platelet count was 64,000/L (baseline 60,000-70,000). He did not have any other bleeding in the body. The medication was finally discontinued. His symptoms improved thereafter. Even though rare, ibrutinib induced hematoma is a serious adverse drug reaction. Once the reason is identified, the treatment should be stopped immediately. A regular follow up is required to observe the progression as the hematoma can be converted to compartment syndrome. As per current guidelines, ibrutinib should be discontinued in case of bleeding of grade>2. Other therapy like Acalabrutinib may be started and the treatment-free period should be kept as short as possible in patients showing the progression of the disease. Acalabrutinib also carries high risk of bleeding in such patients.