Is Continuous Therapy Becoming Finite? The Evolving Landscape of CLL Treatment in 2026
Résumé
The front-line treatment landscape for chronic lymphocytic leukemia (CLL) is rapidly evolving, with several new therapeutic options emerging. Traditionally, chemoimmunotherapy (CIT) formed the foundation of front-line treatment. However, over the past decade, targeted therapies have transformed the management of CLL, replacing CIT as the backbone of front-line treatment. Table 1 summarizes pivotal trials that have advanced CLL treatment.
As a result of these advances, clinicians now have multiple highly effective frontline options. The challenge is no longer selecting the most efficacious regimen but rather selecting the optimal strategy for each individual patient. To address this evolving landscape, this review highlights current evidence and key practical considerations shaping frontline CLL management in Canada.
Références
Kang S, Ahn IE. Prognostic markers in the era of targeted therapies. Acta Haematol. 2024;147(1):33-46.
Burger JA, Barr PM, Robak T, Owen C, Tedeschi A, Sarma A, et al. Final analysis of the RESONATE-2 study: up to 10 years of follow-up of first-line ibrutinib treatment for CLL/SLL. Blood. 2025;146:2168–76.
Woyach JA, Perez BG, Ruppert AS, Miller C, Heerema NA, Zhao W, et al. Follow-up from the A041202 study shows continued efficacy of ibrutinib regimens for older adults with CLL. Blood. 2024;143:1616–27.
Robak T, Witkowska M, Smolewski P. The role of Bruton’s kinase inhibitors in chronic lymphocytic leukemia: current status and future directions. Cancers (Basel). 2022;14(3):771.
Sharman JP, Egyed M, Jurczak W, Skarbnik AP, Patel K, Flinn IW, et al. Acalabrutinib-obinutuzumab improves survival vs chemoimmunotherapy in treatment-naive CLL in the 6-year follow-up of ELEVATE-TN. Blood. 2025;146:1276–85.
Shadman M, Munir T, Robak T, Brown JR, Kahl BS, Ghia P, et al. Zanubrutinib versus bendamustine and rituximab in patients with treatment-naive chronic lymphocytic leukemia/small lymphocytic lymphoma: median 5-year follow-up of SEQUOIA. J Clin Oncol. 2024;43:780–7.
Brown JR, Eichhorst B, Lamanna N, O’Brien SM, Tam CS, Qiu L, et al. Sustained benefit of zanubrutinib vs ibrutinib in patients with R/R CLL/SLL: final comparative analysis of ALPINE. Blood. 2024;144:2706–17.
Brown JR, Eichhorst B, Hillmen P, Jurczak W, Kaźmierczak M, Lamanna N, et al. Zanubrutinib or ibrutinib in relapsed or refractory chronic lymphocytic leukemia. N Engl J Med. 2023;388:319–32.
Al-Sawaf O, Robrecht S, Zhang C, Olivieri S, Chang YM, Fink AM, et al. Venetoclax-obinutuzumab for previously untreated chronic lymphocytic leukemia: 6-year results of the randomized phase 3 CLL14 study. Blood. 2024;144(18):1924-1935.
Fürstenau M, Kater AP, Robrecht S, von Tresckow J, Zhang C, Gregor M, et al. First-line venetoclax combinations versus chemoimmunotherapy in fit patients with chronic lymphocytic leukaemia (GAIA/CLL13): 4-year follow-up from a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2024;25(6):744-759.
Niemann CU, Munir T, Moreno C, Owen C, Follows GA, Benjamini O, et al. Fixed-duration ibrutinib-venetoclax versus chlorambucil-obinutuzumab in previously untreated chronic lymphocytic leukaemia (GLOW): 4-year follow-up from a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2023;24(12):1423-1433.
Ghia P, Barr PM, Allan JN, Siddiqi T, Tedeschi A, Kipps TJ, et al. Final analysis of fixed-duration ibrutinib + venetoclax for chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) in the phase 2 CAPTIVATE study. J Clin Oncol. 2025;43:7036.
Brown JR, Seymour JF, Jurczak W, Aw A, Wach M, Illes A, et al. Fixed-duration acalabrutinib combinations in untreated chronic lymphocytic leukemia. N Engl J Med. 2025;392(8):748–62.
Davids MS, Stilgenbauer S, Tam CS. First-line treatment for CLL in the era of targeted therapy. Blood Cancer J. 2026;16:19.
Shanafelt TD, Wang XV, Kay NE, Hanson CA, O’Brien S, Barrientos J, et al. Ibrutinib–rituximab or chemoimmunotherapy for chronic lymphocytic leukemia. N Engl J Med. 2019;381:432-443.
Munir T, Cairns DA, Bloor A, Allsup D, Cwynarski K, Pettitt A, et al. Chronic lymphocytic leukemia therapy guided by measurable residual disease. N Engl J Med. 2024;390:326-337.
Al-Sawaf O, Stumpf J, Zhang C, Simon F, Bosch F, Feyzi E, et al. Fixed-duration versus continuous treatment for chronic lymphocytic leukemia. N Engl J Med. 2025;394:1084-1096.
Lachaine J, Guinan K, Aw A, Banerji V, Fleury I, Owen C. Impact of fixed-duration oral targeted therapies on the economic burden of chronic lymphocytic leukemia in Canada. Curr Oncol. 2023;30(5):4483-4498.
Jurczak W, Kwiatek M, Czyz J, de Mattos ER, Eom K, Egle A, et al. BRUIN CLL-313: randomized phase iii trial of pirtobrutinib versus bendamustine plus rituximab in untreated patients with chronic lymphocytic leukemia/small lymphocytic lymphoma. J Clin Oncol. 2025;44(6):466-475.
Woyach J, Qiu L, Grosicki S, Wrobel T, Capra M, Czyz J, et al. Pirtobrutinib versus ibrutinib in treatment-naïve and relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma. J Clin Oncol. 2026;44(6):476-485.
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© Actualité hématologique au Canada 2026
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