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2348 Real-World Analysis of Patients with CLL Treated with Ibrutinib: A Retrospective Analysis of the Brazilian Registry of CLL

Program: Oral and Poster Abstracts
Session: 906. Outcomes Research: Lymphoid Malignancies Excluding Plasma Cell Disorders: Poster I
Hematology Disease Topics & Pathways:
Lymphoid Leukemias, CLL, Diseases, Lymphoid Malignancies, Adverse Events
Saturday, December 7, 2024, 5:30 PM-7:30 PM

Verena Pfister1,2*, Fernanda de Morais Marques, MD2,3,4*, Vinicius Campos de Molla, MD, PhD5,6*, Flavia Parra7*, Mihoko Yamamoto, MD2,8*, Rodrigo Santucci9*, Milton A. F. Aranha, MD10*, Valeria Buccheri, MD, PhD11*, Glaciano Ribeiro, MD12*, Vera Figueiredo, MD13*, Nelson Hamerschlak, MD, PhD14, Abel Costa Neto, MD15, Jayr Schmidt Filho, MD16*, Talita Silveira, MD, PhD17*, Adriana Scheliga, MD, MSc18*, Matheus Vescovi Goncalves, MD, PhD8*, Leila Perobelli, MD19*, Carlos Chiattone, MD, PhD20,21 and Celso Arrais-Rodrigues, MD, PhD2,22,23

1Division of Hematology - UNIFESP, Sao Paulo, AC, Brazil
2Brazilian Registry of CLL – Associação Brasileira de Hematologia e Hemoterapia, Sao Paulo, Brazil
3Hospital de Transplantes Euryclides de Jesus Zerbini – Hospital Brigadeiro. São Paulo – Brazil, Sao Paulo, Brazil
4Division of Hematology - UNIFESP. São Paulo – Brazil, São Paulo, Brazil
5Hospital Nove de Julho, DASA, São Paulo, Brazil
6Universidade Federal de São Paulo, São Paulo, Brazil
7Brazilian Registry of CLL – Associação Brasileira de Hematologia e Hemoterapia, Sao Paulo, BRA
8Division of Hematology - UNIFESP. São Paulo – Brazil, Sao Paulo, Brazil
9HEMOMED, Sao Paulo, AM, BRA
10HEMOMED- BRAZIL, São Paulo, BRA
11Instituto do Câncer do Estado de São Paulo/Hospital das Clinicas - Faculdade de Medicina da Universidade de São Paulo, São Paulo -, São Paulo, Brazil
12Universidade Federal de Minas Gerais. Belo Horizonte, Minas Gerais - Brazil, Belo Horizonte, Brazil
13Hospital do Servidor Público do Estado de São Paulo – IAMSPE. São Paulo – Brazil, Sao Paulo, Brazil
14Hematology, Albert Einstein Hospital, São Paulo, Brazil
15Department of Hematology, D'Or Institute for Research and Education, São Paulo, Brazil
16AC Camargo Cancer Center, Sao Paulo, BRA
17AC Camargo Cancer Center, São Paulo, Brazil
18Grupo Oncoclinicas, Rio de Janeiro, BRA
19Hospital de Transplantes Euryclides de Jesus Zerbini / Hospital Brigadeiro, São Paulo, Brazil
20Hospital Samaritano-Higienopolis, Sao Paulo, Brazil
21Santa Casa Medical School of Sao Paulo, Sao Paulo, Brazil
22Division of Hematology - UNIFESP, São Paulo, Brazil
23Hospital Nove de Julho - DASA, São Paulo, Brazil

Introduction: Ibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor approved for all lines of treatment in chronic lymphocytic leukemia (CLL), is associated with increased survival and prolonged response, even in high risk scenarios, with relatively low toxicity compared to chemoimmunotherapy. However, a significant number of patients discontinue therapy due to intolerance and toxicity. It is essential to comprehend the factors contributing to treatment discontinuation and the subsequent impact on clinical outcomes. This is the first large real-world analysis of patients from Latin America.

Objective: This analysis aims to utilize real-world data to assess ibrutinib's effectiveness and to examine factors contributing to discontinuation and the subsequent impact on clinical outcomes in Brazil.

Methods: The Brazilian Registry of CLL is an ambispective non-interventional data collection tool. All patients who received ibrutinib as continuous monotherapy at any therapy line between January 2015 and March 2024, with essential minimum data on patient and treatment characteristics, clinical outcomes, and a minimum follow-up of three months, were included.

Results/Discussion: A total of 278 patients from 29 centers were included. Ibrutinib was used in the first line of treatment (LoT) in 23%, second LoT in 42%, third line in 21%, and fourth or subsequent lines in 14%. The majority were male (63%), with a median age of 68 years (range: 35-95), and most (44%) had significant comorbidities. TP53 mutation or del(17p) status was assessed in 173 patients (62%), with 38 (22%) testing positive. The median duration of ibrutinib treatment was 28 months (range: 6 days - 103 months). The median interval between diagnosis and initiation of ibrutinib was 53 months (range: 0-330), shorter for those in 1st or 2nd lines (40 months) than later lines (89 months). Ibrutinib was discontinued in 51% of cases, primarily due to toxicity (32%), death (29%), disease progression (26%), and other factors (13%). In several cases, ibrutinib was replaced by another BTK inhibitor by the physician’s preference A significant proportion (51%) experienced at least one treatment-related toxicity. Patients in the first or second line had fewer adverse events than those in later lines (46% vs. 59%, P=0.04). Common toxicities included infections (28%), bleeding (11%), hematologic toxicity (9%), cardiac toxicity (5%), and diarrhea (4%). Atrial fibrillation occurred in 5% of cases. Median PFS was not reached. After a median follow-up of 50 months (range: 3-105), PFS was 64% at 4 years, longer for patients in the first or second line compared to later lines (72% vs. 48%, P<0.0001) and in those with del(17p)/TP53 mutations compared to those without (50% vs. 69%, P=0.008). The median time-to-next-treatment (TTNT) was 56 months: 17 months for patients who used ibrutinib for less than 2 years, 47 months for 2-4 years, and 84 months for more than 4 years. Overall survival (OS) at 4 years was 70%, shorter for patients in later lines (57% vs. 77% for 1st or 2nd lines, P=0.006). The most common causes of death were infections in 63% of cases (on ibrutinib in 45%, and after stopping ibrutinib in 18%), disease progression (18%), and cardiac complications (7%).

Conclusions: Ibrutinib shows favorable effectiveness in Brazilian CLL patients across all treatment lines. Intolerance and discontinuation were relatively common, affecting treatment effectiveness, especially in patients receiving ibrutinib late in the disease course, possibly related to cumulative adverse events from previous lines. These results should be interpreted considering the limitations of a registry-based retrospective analysis, including lack of details on comorbidities and the impact of these factors on outcomes and adverse events.

Disclosures: Pfister: Johnson & Johnson: Research Funding. Costa Neto: AstraZeneca: Consultancy, Research Funding; Johnson & Johnson: Consultancy, Research Funding, Speakers Bureau; Regeneron: Research Funding; AbbVie: Research Funding, Speakers Bureau; Roche: Research Funding; Beigene: Research Funding; Eli Lilly and Company: Speakers Bureau; Knight Therapeutics: Speakers Bureau.

*signifies non-member of ASH