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3129 Real-World Outcomes of Second-Line Chronic Lymphocytic Leukemia Treatments: Retrospective Analysis of the Brazilian Registry of CLL

Program: Oral and Poster Abstracts
Session: 642. Chronic Lymphocytic Leukemia: Clinical and Epidemiological: Poster II
Hematology Disease Topics & Pathways:
Lymphoid Leukemias, Research, CLL, Clinical Research, Diseases, therapy sequence, Therapies, real-world evidence, Lymphoid Malignancies, registries
Sunday, December 11, 2022, 6:00 PM-8:00 PM

Marcelo Pitombeira de Lacerda, MD, PhD1,2*, Fernanda de Morais Marques, MD3,4, Verena Pfister5*, Flavia de Carvalho Parra6*, Vinicius Campos de Molla, MD7, Valeria Buccheri, PhD8*, Rafael Dezen Gaiolla, PhD, MD9*, Laura Maria Fogliatto10, Rodrigo Santucci, MD11*, Marcelo Bellesso, MD12*, Sérgio Costa Fortier, MD13*, Talita M. B. Silveira, MD, PhD14,15*, Glaciano Ribeiro, MD16,17*, Nelson Hamerschlak, MD, PhD18, Mihoko Yamamoto, MD, PhD19, Matheus Vescovi Goncalves, MD, PhD6,19,20*, Carlos S. Chiattone, MD, PhD21,22 and Celso Arrais-Rodrigues, MD23

1Universidade da Região de Joinville (UNIVILLE), Joinville, Brazil
2Hospital Municipal São José (HMSJ), Joinville, Brazil
3Division of Hematology, Universidade Federal de São Paulo, Sao Paulo, Sp, Brazil
4Brazilian Registry of CLL, Associação Brasileira de Hematologia e Hemoterapia, Sao Paulo, Brazil
5Division of Hematology, Universidade Federal de São Paulo, Sao Paulo, Brazil
6Brazilian Registry of CLL, Associação Brasileira de Hematologia e Hemoterapia, São Paulo, Brazil
7Hematology Department, UNIFESP, Sao Paulo, Brazil
8Instituto do Cancer do Estado de Sao Paulo (ICESP), Faculdade de Medicina, Universidade de Sao Paulo (FMUSP), São Paulo, Brazil
9Hospital Das Clínicas UNESP, Distrito De Rubiao Junior, Botucatu, BRA
10Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil
11Instituto de Ensino e Pesquisa Sao Lucas - IEP Hemomed, Sao Paulo, SP, Brazil
12Instituto Hemomed de Oncologia e Hematologia, São PAULO, SAO PAULO, Brazil
13Hematology Division, Santa Casa de São Paulo Medical School, Sao Paulo, Brazil
14Hematology Discipline, Santa Casa de São Paulo Medical School, São Paulo, Brazil
15Department of Oncohematology, AC Camargo Cancer Center, Sao Paulo, Brazil
16Clínica Hematologica, Belo Horizonte - Minas Gerais, Brazil
17Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
18Hospital Israelita Albert Einstein, Sao Paolo, Brazil
19Division of Hematology, Universidade Federal de São Paulo, São Paulo, Brazil
20Hematology, Fleury Medicina e Saúde, Sao Paulo, Brazil
21Oncology Nucleus, Samaritano Hospital - Higienopolis, Sao Paulo, Brazil
22Department of Medicine, Santa Casa Medicine School, Sao Paulo, Brazil
23Universidade Federal de São Paulo (UNIFESP), Sao Paulo, Brazil

Introduction: Major advances in the treatment of relapsed-refractory (RR) chronic lymphocytic leukemia (CLL) patients were observed in the last decade with the adoption of targeted agents. While a shift away from chemotherapy is expected, the impact of delayed or unequal access to targeted agents in low- and middle-income countries needs to be uncovered through real-world data.

Objective: To assess the clinical outcomes of second-line treatment in RR CLL patients included in the Brazilian Registry of CLL (BRCLL).

Patients and Methods: This is an observational study of second-line CLL treatments started between January 2006 and December 2021. BRCLL is a prospective non-interventional data collection tool. All participant centers registered their CLL patients online, after study approval at each center’s ethical review board. Diagnosis and staging of included CLL patients were performed in accordance with recommendations from the International Workshop on Chronic Lymphocytic Leukemia (IWCLL).

Results: Four hundred and forty-four CLL patients in second-line were included. Median age at start of second-line treatment was 66 years (range: 23-93), and 264 were male (59%). At CLL diagnosis, Binet staging was A in 139 patients (36%), B in 139 (36%), and C in 107 (28%). High beta-2-microglobulin levels at diagnosis were found in 58%, and unmutated IGHV was observed in 61% of patients. At diagnosis, FISH was performed in 166 patients (37%), of which 33 patients had del(17p) (20%). The most commonly prescribed second-line treatments were: FC (+/- R) in 160 patients (36%); chlorambucil (+/- R) in 109 (25%); ibrutinib in 63 (14%); CHOP/CVP (+/- R) in 62 (14%); monoclonal antibodies (+/- steroids) in 33 (7%); allogeneic stem cell transplantation in 9 (2%) and venetoclax in 8 (2%). Forty patients (9%) were treated in clinical trials. Median follow-up after second-line treatment was 34 months (range: 3-176). Median time-to-next treatment (TTNT) was 28 months. TTNT was statistically longer in patients who received second-line with ibrutinib or venetoclax in comparison with FC or chlorambucil +/- anti-CD20 (not reached versus 29 months, p<0.0001) or those who received other regimens (CHOP or CVP +/- anti-CD20, monoclonal antibodies +/- steroids – 12 months, p<0.0001). Higher 3-year treatment-free survival (TFS) was also observed with ibrutinib or venetoclax (69% versus 41% and 23%, respectively, p<0.0001). Among patients included in clinical trials, 3-year TFS was also higher (70% versus 38%, p<0.0001). TFS for patients receiving allogeneic stem cell transplantation was 86% at 3 years. Overall survival (OS) probability at 3 years was 71%. OS was significantly shorter in those who received other regimens (CHOP/CVP-like or monoclonal antibodies +/- steroids – 53%), in comparison with those who received ibrutinib or venetoclax (80%, p<0.0001), or FC/chlorambucil-based chemotherapy (69%, p=0.01).

Conclusion: Over the reported period, second-line CLL treatments in Brazil were mostly chemotherapy- or chemoimmunotherapy-based, with unfavorable outcomes associated with CHOP/CVP-like regimens or monoclonal antibodies +/- steroids. While the adoption of targeted therapies was associated with longer TTNT and OS, access to these agents is still very limited in the public setting.

Disclosures: Bellesso: AstraZeneca: Research Funding. Chiattone: Takeda Oncology Brazil: Research Funding.

*signifies non-member of ASH