Treatment pattern of chronic lymphocytic leukemia/small lymphocytic lymphoma in Korea: a multicenter retrospective study (KCSG LY20-06)
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Background/Aims: Little attention is paid to chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) in Korea due to the rarity of the disease. With its rising incidence, we aimed to evaluate recent changes in treatment patterns and survival outcomes of patients with CLL/SLL. Methods: A total of 141 patients diagnosed with CLL/SLL between January 2010 and March 2020 who received systemic therapy were analyzed in this multicenter retrospective study. Results: The median patient age was 66 years at diagnosis, and 68.1% were male. The median interval from diagnosis to initial treatment was 0.9 months (range: 0–77.6 months), and the most common treatment indication was progressive marrow failure (50.4%). Regarding first-line therapy, 46.8% received fludarabine, cyclophosphamide, plus rituximab (FCR), followed by chlorambucil (19.9%), and obinutuzumab plus chlorambucil (GC) (12.1%). The median progression-free survival (PFS) was 49.3 months (95% confidence interval [CI], 32.7–61.4), and median overall survival was not reached (95% CI, 98.4 mo– not reached). Multivariable analysis revealed younger age (≤ 65 yr) (hazard ratio [HR], 0.46; p < 0.001) and first-line therapy with FCR (HR, 0.64; p = 0.019) were independently associated with improved PFS. TP53 aberrations were observed in 7.0% (4/57) of evaluable patients. Following reimbursement, GC became the most common therapy among patients over 65 years and second in the overall population after 2017. Conclusions: Age and reimbursement mainly influenced treatment strategies. Greater effort to apply risk stratifications into practice and clinical trials for novel agents could help improve treatment outcomes in Korean patients.
Abstract
Background/Aims: Little attention is paid to chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) in Korea due to the rarity of the disease. With its rising incidence, we aimed to evaluate recent changes in treatment patterns and survival outcomes of patients with CLL/SLL. Methods: A total of 141 patients diagnosed with CLL/SLL between January 2010 and March 2020 who received systemic therapy were analyzed in this multicenter retrospective study. Results: The median patient age was 66 years at diagnosis, and 68.1% were male. The median interval from diagnosis to initial treatment was 0.9 months (range: 0–77.6 months), and the most common treatment indication was progressive marrow failure (50.4%). Regarding first-line therapy, 46.8% received fludarabine, cyclophosphamide, plus rituximab (FCR), followed by chlorambucil (19.9%), and obinutuzumab plus chlorambucil (GC) (12.1%). The median progression-free survival (PFS) was 49.3 months (95% confidence interval [CI], 32.7–61.4), and median overall survival was not reached (95% CI, 98.4 mo– not reached). Multivariable analysis revealed younger age (≤ 65 yr) (hazard ratio [HR], 0.46; p < 0.001) and first-line therapy with FCR (HR, 0.64; p = 0.019) were independently associated with improved PFS. TP53 aberrations were observed in 7.0% (4/57) of evaluable patients. Following reimbursement, GC became the most common therapy among patients over 65 years and second in the overall population after 2017. Conclusions: Age and reimbursement mainly influenced treatment strategies. Greater effort to apply risk stratifications into practice and clinical trials for novel agents could help improve treatment outcomes in Korean patients.
참고문헌 (30)
- Kay NE, "CLL update 2022 : a continuing evolution in care", Blood Rev, 54, pp.100930~ (2022)
- International CLL-IPI working group, "An international prognostic index for patients with chronic lymphocytic leukaemia(CLL-IPI) : a meta-analysis of individual patient data", Lancet Oncol, 17, pp.779~790 (2016)
- Condoluci A, "International prognostic score for asymptomatic early-stage chronic lymphocytic leukemia", Blood, 135, pp.1859~1869 (2020)
- von Tresckow J, "Sequential treatment with bendamustine, obinutuzumab(GA101)and Ibrutinib in chronic lymphocytic leukemia(CLL) : final results of the CLL2-BIG trial", Leukemia, 36, pp.2125~2128 (2022)
- Kater AP, "Fixed duration of venetoclax-rituximab in relapsed", refractory chronic lymphocytic leukemia eradicates minimal residual disease and prolongs survival : post-treatment follow-up of the MURANO phase III study, 2019, pp.37, 269~277
- Iovino L, "Novel therapies in chronic lymphocytic leukemia : a rapidly changing landscape", Curr Treat Options Oncol, 21, pp.24~ (2020)
- Ou Y, "Trends in disease burden of chronic lymphocytic leukemia at the global, regional, and national levels from 1990 to 2019, and projections until 2030 : a population-based epidemiologic study", Front Oncol, 12, pp.840616~ (2022)
- Döhner H, "Genomic aberrations and survival in chronic lymphocytic leukemia", N Engl J Med, 343, pp.1910~1916 (2000)
- Landau DA, "Mutations driving CLL and their evolution in progression and relapse", Nature, 526, pp.525~530 (2015)
- Vardell VA, "Influence of racial and ethnic identity on overall survival in patients with chronic lymphocytic leukemia", Am J Hematol (2023)[DOI]
- Jang MA, "Chronic lymphocytic leukemia in Korean patients : frequent atypical immunophenotype and relatively aggressive clinical behavior", Int J Hematol, 97, pp.403~408 (2013)
- Yunsuk Choi, "Treatment outcome and prognostic factors of Korean patients with chronic lymphocytic leukemia: a multicenter retrospective study", The Korean Journal of Internal Medicine, 36(1), pp.194~204 (2021), 대한내과학회[DOI]
- Jun Ho Yi, "Multicenter retrospective analysis of patients with chronic lymphocytic leukemia in Korea", Blood Research, 56(4), pp.243~251 (2021), 대한혈액학회[DOI]
- Hallek M, "iwCLL guidelines for diagnosis, indications for treatment, response assessment, and supportive management of CLL", Blood, 131, pp.2745~2760 (2018)
- Campo E, "The 2008 WHO classification of lymphoid neoplasms and beyond : evolving concepts and practical applications", Blood, 117, pp.5019~5032 (2011)
- "Cancer fact sheets:chronic lymphocytic leukemia (CLL)"[URL]
- Eichhorst B, "First-line chemoimmunotherapy with bendamustine and rituximab versus fludarabine, cyclophosphamide, and rituximab in patients with advanced chronic lymphocytic leukaemia (CLL10): an international, open-label, randomised, phase 3, non-inferiority trial", Lancet Oncol, 17, pp.928~942 (2016)
- Gunawardana C, "South Asian chronic lymphocytic leukaemia patients have more rapid disease progression in comparison to White patients", Br J Haematol, 142, pp.606~609 (2008)
- Ko BS, "Epidemiology, treatment patterns and survival of chronic lymphocytic leukaemia", small lymphocytic lymphoma(CLL, Int J Clin Pract, pp.2021, 75[DOI]
- Sylvan SE, "First-line therapy in chronic lymphocytic leukemia : a Swedish nation-wide real-world study on 1053 consecutive patients treated between 2007 and 2013", Haematologica, 104, pp.797~804 (2019)
- Jain P, "Richter’s transformation in chronic lymphocytic leukemia", Oncology(Williston Park), 26, pp.1146~1152 (2012)
- Laribi K, "Therapy-related myeloid neoplasms in patients with chronic lymphocytic leukemia who received FCR", FC as frontline therapy, 2022, pp.6, e716~
- Oscier DG, "Multivariate analysis of prognostic factors in CLL : clinical stage, IGVH gene mutational status, and loss or mutation of the p53 gene are independent prognostic factors", Blood, 100, pp.1177~1184 (2002)
- O’Brien S, "Ibrutinib for patients with relapsed or refractory chronic lymphocytic leukaemia with 17p deletion(RESONATE-17) : a phase 2, open-label, multicentre study", Lancet Oncol, 17, pp.1409~1418 (2016)
- "Chronic lymphocytic leukemia/small lymphocytic lymphoma" (2022)[URL]
- Campo E, "TP53 aberrations in chronic lymphocytic leukemia : an overview of the clinical implications of improved diagnostics", Haematologica, 103, pp.1956~1968 (2018)
- Tedeschi A, "Do age, fitness, and concomitant medications influence management and outcomes of patients with CLL treated with ibrutinib?", Blood Adv, 5, pp.5490~5500 (2021)
- Seung SJ, "Examining treatment patterns and real-world outcomes in chronic lymphocytic leukemia using administrative data in Ontario", Curr Oncol, 28, pp.4832~4844 (2021)
- Ranti J, "Characterization of real-world treatment practices and outcomes among patients with chronic lymphocytic leukemia treated in a Finnish tertiary center", EJHaem, 3, pp.291~300 (2021)
- Pfister V, "Lower access to risk stratification tests and drugs, and worse survival of chronic lymphocytic leukaemia patients treated in public as compared to private hospitals in Brazil : a retrospective analysis of the Brazilian registry of chronic lymphocytic leukaemia", EJHaem, 3, pp.698~706 (2022)