Clinico-economic burden of first-line chemoimmunotherapy by risk status in chronic lymphocytic leukemia
Abstract
Objective: This study was conducted to evaluate the trend in cytogenetic/molecular testing rate in chronic lymphocytic leukemia (CLL) and assess the clinical and economic burden of first-line treatment with chemoimmunotherapy by risk status.
Methods: Medical charts linked with claims for adults with CLL treated with first-line chemoimmunotherapy between 1/1/2007 and 7/31/2019.
Results: Testing increased from 30% to 44% from 2007 to 2019. High-risk patients (n=119; defined as having del(17p), del(11q), TP53 mutation, unmutated IGHV or complex karyotype) had 65% higher risk of next treatment or death, 65% higher risk of treatment failure, and 33% higher costs during first-line treatment than non-high risk patients (n=134).
Conclusion: High-risk CLL patients treated with first-line chemoimmunotherapy have poorer clinical and economic outcomes compared to non-high risk patients. Assessment of genetic risk remains suboptimal.
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References
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[2] S. Molica, Sex differences in incidence and outcome of chronic lymphocytic leukemia patients. Leuk Lymphoma 47 (2006) 1477-1480.
[3] L.M. Morton, S.S. Wang, S.S. Devesa, et al, Lymphoma incidence patterns by WHO subtype in the United States, 1992-2001. Blood 107 (2006) 265-276.
[4] J.L. Binet, A. Auquier, G. Dighiero, et al, A new prognostic classification of chronic lymphocytic leukemia derived from a multivariate survival analysis. Cancer 48 (1981) 198-206.
[5] R.N. Damle, T. Wasil, F. Fais, et al, Ig V gene mutation status and CD38 expression as novel prognostic indicators in chronic lymphocytic leukemia. Blood 94 (1999) 1840-1847.
[6] T.D. Shanafelt, Predicting clinical outcome in CLL: how and why. Hematology Am Soc Hematol Educ Program (2009) 421-429.
[7] J.A. Cohen, R. Bomben, F. Pozzo, et al, An updated perspective on current prognostic and predictive biomarkers in chronic lymphocytic leukemia in the context of chemoimmunotherapy and novel targeted therapy. Cancers 12 (2020) 894.
[8] T. Zenz, S. Frohling, D. Mertens, et al, Moving from prognostic to predictive factors in chronic lymphocytic leukaemia (CLL). Best Pract Res Clin Haematol 23 (2010) 71-84.
[9] T. Zenz, D. Mertens, R. Kuppers, et al, From pathogenesis to treatment of chronic lymphocytic leukaemia. Nat Rev Cancer 10 (2010) 37-50.
[10] P. Baliakas, M. Iskas, A. Gardiner, et al. Chromosomal translocations and karyotype complexity in chronic lymphocytic leukemia: a systematic reappraisal of classic cytogenetic data. Am J Hematol 89 (2014) 249-55.
[11] Y. Le Bris, S. Struski, R. Guièze, et al. Major prognostic value of complex karyotype in addition to TP53 and IGHV mutational status in first‐line chronic lymphocytic leukemia. Hematological oncology 35 (2017) 664-70.
[12] D. Rossi, S. Rasi, V. Spina, et al. Integrated mutational and cytogenetic analysis identifies new prognostic subgroups in chronic lymphocytic leukemia. Blood 121(2013) 1403-12.
[13] H. Dohner H, S. Stilgenbauer, A. Benner, et al. Genomic aberrations and survival in chronic lymphocytic leukemia. N Engl J Med 343 (2000) 1910-1916.
[14] T.J. Hamblin, Z. Davis, A. Gardiner, et al. Unmutated Ig V(H) genes are associated with a more aggressive form of chronic lymphocytic leukemia. Blood 94 (1999) 1848-1854.
[15] M. Hallek, Chronic lymphocytic leukemia: 2020 update on diagnosis, risk stratification and treatment. Am J Hematol 94 (2019) 1266–1287.
[16] M. Hallek, K. Fischer, G. Fingerle-Rowson, et al, Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: a randomised, open-label, phase 3 trial. Lancet 376 (2010) 1164-1174.
[17] S. Stilgenbauer, A. Schnaiter, P. Paschka, et al, Gene mutations and treatment outcome in chronic lymphocytic leukemia: results from the CLL8 trial. Blood 123 (2014) 3247-54.
[18] M. Hallek, B.D. Cheson, D. Catovsky, et al. iwCLL guidelines for diagnosis, indications for treatment, response assessment, and supportive management of CLL. Blood 131 (2018) 2745-2760.
[19] National Comprehensive Cancer Network, NCCN Clinical Practice Guidelines in Oncology. Non-Hodgkin's Lymphomas. Version 4.2014. (2014).
[20] National Comprehensive Cancer Network, NCCN Clinical Practice Guidelines in Oncology. Chronic Lymphocytic Leukemia/Small Lymphocytic Leukemia. Version 1.2017. (2016).
[21] National Comprehensive Cancer Network, NCCN Clinical Practice Guidelines in Oncology. Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma. Version 1.2018. (2017).
[22] A. Mato, C. Nabhan, N.E. Kay, et al, Prognostic Testing Patterns and Outcomes of Chronic Lymphocytic Leukemia Patients Stratified by Fluorescence In Situ Hybridization/Cytogenetics: A Real-world Clinical Experience in the Connect CLL Registry. Clin Lymphoma Myeloma Leuk 18 (2018) 114-124 e112.
[23] A.R. Mato, J.C. Barrientos, J.P. Sharman, et al, Real-World Prognostic Biomarker Testing, Treatment Patterns and Dosing Among 1461 Patients (pts) with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) from the informCLL Prospective Observational Registry. Blood 136 (2020) (Supplement 1), 42-43.
[24] B. Emond, M. Sundaram, H. Romdhani, et al, Comparison of Time to Next Treatment, Health Care Resource Utilization, and Costs in Patients with Chronic Lymphocytic Leukemia Initiated on Front-line Ibrutinib or Chemoimmunotherapy. Clin Lymphoma Myeloma Leuk 19 (2019) 763-775 e762.
[25] Q. Huang, S. Borra, J. Li J, et al, Time to Next Treatment, Health Care Resource Utilization, and Costs Associated with Ibrutinib Use Among U.S. Veterans with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: A Real-World Retrospective Analysis. J Manag Care Spec Pharm 26 (2020) 1266-1275.
[26] Q. Huang, B. Emond, M.H. Lafeuille, et al, Healthcare resource utilization and costs associated with first-line ibrutinib compared to chemoimmunotherapy treatment among Medicare beneficiaries with chronic lymphocytic leukemia. Curr Med Res Opin 36 (2020) 2009-2018.
[27] A.R. Mato, J.C. Barrientos, N. Ghosh, et al, Prognostic Testing and Treatment Patterns in Chronic Lymphocytic Leukemia in the Era of Novel Targeted Therapies: Results From the informCLL Registry. Clin Lymphoma Myeloma Leuk 20 (2020), 174-183 e173.
[28] A. Mato, C. Nabhan, N.E. Kay, et al, Real-world clinical experience in the Connect((R)) chronic lymphocytic leukaemia registry: a prospective cohort study of 1494 patients across 199 US centres. Br J Haematol 175 (2016) 892-903.
[29] P.A. Thompson, C.S. Tam, S.M. O’Brien, et al, Fludarabine, cyclophosphamide, and rituximab treatment achieves long-term disease-free survival in IGHV-mutated chronic lymphocytic leukemia. Blood 127 (2016) 303-309.
[30] S. Stilgenbauer, A. Schnaiter, P. Paschka, et al. Gene mutations and treatment outcome in chronic lymphocytic leukemia: results from the CLL8 trial. Blood 123 (2014) 3247-3254.
[31] Q. Huang, K.L. Deering, Q. Harshaw, et al, Clinical Outcomes Among Real-World Patients with Chronic Lymphocytic Leukemia (CLL) Initiating First-Line Ibrutinib or Chemoimmunotherapy (CIT) Stratified By Risk Status: Results from a US Retrospective Chart Review Study. Blood 136 (2020) (Supplement 1) 16-18.
[32] C. Nabhan, D. Nero, C.H. Lee, et al, Cost-Effectiveness Comparison between Ibrutinib, Chemotherapy, and Chemoimmunotherapy in Front-Line Treatment of Chronic Lymphocytic Leukemia (CLL). Blood 132 (2018) (Supplement 1) 4757-4757.
[33] S. Wang S, M.H. Lafeuille, P. Lefebvre, et al, Economic burden of treatment failure in chronic lymphocytic leukemia patients. Curr Med Res Opin 34 (2018) 1135-1142.
Authors
Leslie, L. A., Gangan, N., Tan, H., Huang, Q., & Yan, J. (2022). Clinico-economic burden of first-line chemoimmunotherapy by risk status in chronic lymphocytic leukemia. Journal of Current Medical Research and Opinion, 5(05). Retrieved from http://cmro.in/index.php/jcmro/article/view/520
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