Real-World Analysis of Patients with CLL treated with Ibrutinib: A Retrospective Analysis of Brazilian Registry of CLL Open Access

• Ibrutinib shows favorable efficacy across all lines of treatment. However, intolerance and discontinuation are common.

Although ibrutinib improves survival and prolongs responses with less toxicity than chemoimmunotherapy, some patients still discontinue treatment due to intolerance and toxicity. This study is the first large real-world analysis of Latin American patients and included 310 patients from 32 centers. Ibrutinib was administered in first-line therapy for 25% of patients, second-line therapy for 42%, third-line therapy for 20%, and fourth- or later-line therapy for 13%. The median duration of treatment was 29 months. Treatment was discontinued in 55% of patients, most often due to progression (33%), toxicity (32%), or death during treatment (26% of discontinuations). Subsequent treatment varied according to the reason for discontinuation. Treatment-related toxicity occurred in 51% of patients, with higher (59%) in third or later lines than in first or second lines (42%). Common toxicities included infections, bleeding, hematological and cardiac problems and diarrhea. After a median follow-up of 50 months, time to next treatment at 4 years was significantly shorter in patients who received ibrutinib in later lines (48%) compared to patients who received ibrutinib in first or second line (72%). Overall survival was 68% at 4 years. Deaths were mainly due to infections, disease progression and cardiac complications. Ibrutinib shows favorable efficacy in Brazilian CLL patients across all treatment lines. However, intolerance and discontinuation are common, especially in later lines. These findings highlight the need for medical education strategies aimed at preventing unnecessary treatment discontinuation and supporting adherence, especially in the context of adverse events.