A panel of leading oncologists recently discussed treatment approaches for a challenging case of relapsed chronic lymphocytic leukemia (CLL), highlighting the complexities of managing high-risk patients with significant comorbidities.
The case centered on a 70-year-old man who relapsed 24 months after completing first-line venetoclax plus obinutuzumab therapy. The patient presented with complex cytogenetics including del(11q), unmutated IGHV status, and significant cardiovascular disease, including previous myocardial infarction requiring stents.
Treatment Decision Points
Dr. Nakhle Saba of Tulane Cancer Center outlined the key therapeutic options available: retreatment with venetoclax-obinutuzumab or switching to a BTK inhibitor (BTKI). The panel's discussion revealed varying approaches based on different clinical considerations.
"The duration of remission that would trigger retreatment with venetoclax-based therapy is subjective. There's no real guidance on the minimum duration of remission," explained Dr. Saba. Some clinicians consider two years of remission adequate for venetoclax retreatment, while others prefer longer intervals of 3-4 years.
Cardiovascular Risk Management
The patient's cardiac history emerged as a crucial factor in treatment selection. Dr. Vrushali Dabak advocated for venetoclax-obinutuzumab retreatment, citing concerns about BTKI-associated atrial fibrillation risk. However, Dr. Mohammad Muhsin Chisti countered that newer BTKIs like acalabrutinib have shown lower cardiac risk profiles.
BTK Inhibitor Selection
For physicians favoring the BTKI approach, the choice between available agents prompted detailed discussion of recent clinical evidence. Dr. Dabak highlighted data from the ALPINE trial demonstrating zanubrutinib's superior efficacy over ibrutinib in relapsed CLL patients.
"Both acalabrutinib and zanubrutinib were safer than ibrutinib," noted Dr. Saba, referencing recent comparative trials. The panel emphasized that ibrutinib is no longer a preferred treatment option according to current NCCN guidelines.
Genetic Considerations
The presence of del(11q) sparked additional discussion about treatment selection. Dr. Tim Cox raised the observation that patients with del(11q) often show particularly good responses to BTKIs, though Dr. Saba clarified that this factor may be less critical than other genetic markers like TP53 mutations in the relapsed setting.
Strategic Treatment Sequencing
Dr. Robert Bloom offered a perspective on long-term treatment planning: "Just because we don't use venetoclax now doesn't mean we may not use it down the road." This approach preserves future treatment options, including newer agents like pirtobrutinib for subsequent lines of therapy.
The case discussion underscores the nuanced decision-making required in managing relapsed CLL, where treatment selection must balance factors including prior therapy response, genetic risk factors, comorbidities, and the expanding array of available targeted agents.
