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Ibrutinib Discontinuation and Risk of Disease Progression: Two Case Studies

By: Cordi Craig, MS
Posted: Monday, November 22, 2021

Pier Luigi Zinzani, MD, PhD, of the University of Bologna, Italy, and colleagues reported two cases of patients with chronic lymphocytic leukemia (CLL) who, following temporary discontinuation of ibrutinib treatment, experienced rapid disease progression and transformation. In both cases, ibrutinib treatment was eventually resumed, and disease progression was resolved. The case presentations were published in Leukemia & Lymphoma.

The first patient was a 60-year-old man; after being diagnosed in July 2017 with his second disease relapse, he was started on ibrutinib. In January 2019, ibrutinib was discontinued due to a flu-like syndrome. Treatment was resumed within 2 weeks but stopped again due to grade 4 neutropenia. A CT scan showed a rapid increase in cervical lymph nodes and an enlarged spleen. A significant percentage of prolymphocytes were also recorded. Once ibrutinib was restored at a lower dose, the patient’s spleen size improved, and the prolymphocytes were no longer detected in peripheral blood samples.

The second patient was a 73-year-old man, diagnosed with CLL in 2017 after a bone marrow biopsy. In August 2018, the patient began second-line ibrutinib. Approximately 1 year later, ibrutinib treatment was discontinued due to worsening leukopenia and thrombocytopenia. Following treatment discontinuation, the clinicians observed a steep increase in serum lactate dehydrogenase (LDH) concentrations and peripheral blood prolymphocytes. After a bone marrow biopsy, the patient was diagnosed with Richter syndrome. When ibrutinib treatment was resumed, peripheral blood leukocytes and platelet counts increased and LDH levels normalized. Both patients were eventually transitioned to venetoclax treatment.

The opportunity for ibrutinib discontinuation, even temporary, should be thoroughly evaluated. Patient compliance to treatment is critical because even temporary treatment discontinuation may induce clinically severe flare-ups. In addition, treatment discontinuation due to surgical needs should be evaluated on an individual basis to prevent the risk of disease progression.

Disclosure: The study authors reported no conflicts of interest.



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