KINASE INHIBITORS

Presentation and Diagnosis

A 72-year-old male is diagnosed with intermediate-risk Rai stage III chronic lymphocytic leukemia (CLL) after presenting with fatigue, palpable cervical and axillary lymph nodes, and 10% weight loss over the course of 3 months. Labs reveal a WBC 32,000, hemoglobin 9.1 g/dL, platelets 102,000, and lymphoid predominance. Peripheral blood flow cytometry identifies a monoclonal B-cell population consistent with CLL immunophenotype. Prognostic workup reveals IGHV-unmutated and del(11q) by FISH panel from peripheral blood. Spleen palpable 2 cm below left costal margin on exam. CT NTAP shows diffuse non-bulky lymphadenopathy (<5 cm) and splenomegaly 19 cm. Bone marrow biopsy with aspirate is 80% cellular with 70% CLL infiltration and normal karyotype. His past medical history includes diabetes mellitus, osteoarthritis, and hypertension. Current medications include metformin and lisinopril.

Treatment Course

Based on age, comorbidities, and risk stratification, the patient is initiated on ibrutinib 420 mg daily. Restaging studies at 3 months confirm partial response.

Cardiovascular Toxicity Mitigation and Management

Serial blood pressure measurements during the initial 6 months of treatment show increasing blood pressure. Lisinopril dose is increased.

After 1 year on ibrutinib, the patient presents to the ER with fever of 102° F, productive cough, and dyspnea. Vital signs show pulse 150 bpm, pulse oximetry 88%, and blood pressure 100/90. ECG reveals atrial fibrillation with rapid ventricular response. ECHO reveals a LVEF 55-60%, and CT chest confirms right middle lobe pneumonia. Ibrutinib is held during admission while the patient receives antibiotics for pneumonia and pharmacologic conversion to normal sinus rhythm. He is discharged on metoprolol, apixaban, and lisinopril. Given clinical and hematologic benefit with ibrutinib, he resumes ibrutinib 420 mg daily. Follow-up CT chest shows resolution of pneumonia.

The advanced practitioner collaborates with cardio-oncology to ensure that the patient receives ongoing cardiac monitoring and medication management. The patient is educated on his increased risk for bleeding-related complications with concomitant apixaban and ibrutinib. He is instructed to maintain a blood pressure diary, and to report SBP >140 and DBP >90.