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Individualization of frontline chronic lymphocytic leukaemia treatment –⁠ a comprehensive view on risk stratification in the era of targeted therapy


Authors: A. Panovská
Authors‘ workplace: Interní hematologická a onkologická klinika LF MU a FN Brno
Published in: Transfuze Hematol. dnes,32, 2026, No. 2, p. 98-104.
Category: Review/Educational Papers
doi: https://doi.org/10.48095/cctahd202610

Overview

Over the past decade, the treatment of chronic lymphocytic leukaemia (CLL) has undergone a fundamental transformation, driven by a deeper understanding of disease biology –⁠ particularly at the level of molecular genetic alterations and key signalling pathways. Targeted agents acting on the B-cell receptor (notably Bruton tyrosine kinase inhibitors) and on apoptotic regulation (BCL-2 protein inhibitors) have progressively replaced chemoimmunotherapy as the standard first-line approach. The article by E. Tausch and colleagues, published in the Hematology 2024 education issue (from the Annual Meeting of the American Society of Hematology), offers a comprehensive overview of current strategies for risk stratification and the selection of targeted first-line therapy for patients with CLL. The authors summarize diagnostic recommendations, the role of molecular genetic markers (particularly IGHV mutational status, 17p deletion, and TP53 mutation), and compare results from major phase III randomized trials. Emphasis is placed on the individualization of therapy based on genetic risk, comorbidities, and other patient-specific factors. These postulates should be implemented into the standard of care for patients with CLL in Czechia.

Keywords:

chronic lymphocytic leukaemia – BTK inhibitors – frontline therapy – BCL-2 inhibitors – individualization of treatment


Sources

1. Tausch E, Schneider C, Stilgenbauer S. Risk-stratification in frontline CLL therapy: standard of care. Hematology Am Soc Hematol Educ Program. (2024); 2024 (1): 457–466.

2. Hallek M, Cheson BD, Catovsky D, et al. iwCLL guidelines for diagnosis, indications for treatment, response assessment, and supportive management of CLL. Blood. 2018; 131 (25): 2745–2760.

3. Špaček M, Šimkovič M, Pospíšilová Š, et al. Doporučení pro diagnostiku a léčbu chronické lymfocytární leukemie. [online]. Publikováno 28. 4. 2026. Dostupné z: https: //cll.cz/sites/default/files/2026-05/Doporuceni%20CLL%2028042026.pdf

4. Wierda WD, Brown J, Abramson JS, et al. Chronic lymphocytic leukemia/small lymphocytic lymphoma,Version 2.2024, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2024; 22 (3): 175–204.

5. Sharman JP, Egyed M, Jurczak W, et al. Acalabrutinib with or without obinutuzumab versus chlorambucil and obinutuzumab for treatment-naive chronic lymphocytic leukemia (ELEVATE-TN): a randomised, conrolled, phase 3 trial. Lancet. 2020; 395 (10232): 1278–1291.

6. Woyach JA, Perez Burbano G, Ruppert AS, et al. Follow-up from the A041202 study shows continued efficacy of ibrutinib regimens for older padults with CLL. Blood. 2024; 143 (16): 1616–1627.

7. Fischer K, Al-Sawaf O, Bahlo J, et al. Venetoclax and obinutuzumab in patients with CLL and coexisting conditions. N Engl J Med. 2019; 380 (23): 2225–2236.

8. Neimann CU, Munir T, Moreno C, et al. Fixed-duration ibrutinib-venetoclax versus chlorambucil-obinutuzumab in previously untreated chronic lymphocytic leukemia (GLOW): 4-year follow-up from a multicentre, open-label, randomised phase 3 trial. Lancel Oncol. 2023; 24 (12): 1423–1433.

9. Tam CS, Brown JR, Kahl BS, et al. Zanubrutinib versus bendamustine and rituximab in untreated chronic lymphocytic leukaemia and small lymphocytic lymphoma (SEQUOIA): a randomised, controlled, phase 3 trial. Lancet Oncol. 2022; 23 (8): 1031–1043.

10. Munir T, Cairns DA, Bloor A, et al. National Cancer Research Institute Chronic Lymphocytic Leukemia Subgroup. Chronic lymphocytic leukemia therapy guided by measurable residual disease. N Engl J Med. 2024; 390 (4): 326–337.

11. Al-Sawaf O, Robrecht S, Zhang C, et al. Venetoclax-obinutuzumab for previously untreated chronic lymphocytic leukemia: 6-year results of the phase 3 CCL14 study. Blood. 2024; 144 (18): 1924–1935.

12. Thompson PA, Bazinet A, Wierda WG, et al. Sustained remissions in CLL after frontline FCR treatment with very-long-term follow-up. Blood. 2023; 142 (21): 1784–1788.

13. Byrd JC, Hillmen P, Ghia P, et al. Acalabrutinib versus ibrutinib in previously treated chronic lymphocytic leukemia: results of the first randomized phase III trial. J Clin Oncol. 2021; 39 (31): 3441–3452.

14. Brown JR, Eichhorst B, Hillmen P, et al. Zanubrutinib or ibrutinib in relapsed or refractory chronic lymphocytic leukemia. N Eng J Med. 2023; 388 (4): 219–332.

15. Moreno C, Greil R, Demirkan F, et al. First-line treatment of chronic lymphocytic leukemia with ibrutinib plus obinutuzumab versus chlorambucil plus obinutuzumab: final analysis of the randomized, phase III iLLUMINATE trial. Haematologica. 2022; 107 (9): 2108–2120.

16. Tam CS, Allan JN, Siddiqi T, et al. Fixed-duration ibrutinib plus venetoclax for first-line treatment of CLL: primary analysis of the CAPTIVATE FD cohort. Blood. 2022; 139 (22): 3277–3289.

17. Kater AP, Owen C, Moreno C, et al. Fixed-duration ibrutinib-venetoclax in patients with chronic lymphocytic leukemia and comorbidities. NEJM Evid. 2022; 1 (7): EVIDoa2200006.

18. Shanafelt TD, Wang XV, Hanson CA, et al. Long-term outcomes for ibrutinib-rituximab and chemoimmunotherapy in CLL: updated results of E1912 trial. Blood. 2022; 140 (2): 112–120.

19. Moreno C, Munir T, Owen C, et al. First-line fixed-duration ibrutinib plus venetoclax (Ibr+Ven) versus chlorambucil plus obinutuzumab (Clb+O): 55-month follow-up from the glow study. Blood. 2023; 142 (Suppl 1): 634.

20. Fürstenau M, Kater AP, Robrecht S, et al. First-line venetoclax combinations versus chemoimmunotherapy in fit patients with chronic lymphocytic leukemia (GAIA/CLL13): 4-year follow-up from a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2024; 25 (6): 744–759.

21. Thompson MC, Harrup RA, Coombs CC, et al. Venetoclax retreatment of patients with chronic lymphocytic leukemia after previous venetoclax-based regimen. Blood Adv. 2022; 6 (15): 4553–4557.

Labels
Haematology Internal medicine Clinical oncology

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