The management of modern targeted therapy for CLL in a patient with significant cardiac comorbidities—a case report

A 61-year-old Caucasian woman was first seen with an incidental diagnosis of chronic lymphocytic leukemia (CLL), presenting with only moderately increased lymphocyte count and minimal thrombocytopenia. The patient showed no significant disease-related symptoms Complicating further management, there was a history of arterial hypertension and both atrial fibrillation and atrial flutter.

At the initial diagnosis, a “watchful waiting” approach was initiated; however, the patient quickly progressed to be in need of CLL treatment. At the time of treatment initiation, the Bruton kinase inhibitor (BTKi) ibrutinib was the only modern substance approved for first-line treatment of CLL. Therefore, although there was a significant risk of cardiac side effects, ibrutinib was started and led to excellent disease control.

The treatment with ibrutinib led to an increase in the frequency and severity of episodes of atrial fibrillation. Both pharmacological and interventional treatments were not sufficient to control these episodes, and therefore treatment was switched to acalabrutinib, a second-generation-BTKi, as soon as it became available.

This quickly led to a significant improvement in symptom load, and treatment with the second-generation BTKi acalabrutinib could be commenced for a further 18 months. Then, severe myalgia and arthralgia led to the end of this treatment. After a treatment-free interval of more than 2 years, the patient warranted further treatment and rituximab/venetoclax was initiated.

Our case shows that even with good efficacy, the side effects of modern therapies can lead to early discontinuation of treatment, relatively quick progression to further treatments, and therefore suboptimal outcomes for the patient. Further work to optimize the management of even such “benign” side effects as myalgia/arthralgia is needed.