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New Treatment Options for Newly-Diagnosed and Relapsed Chronic Lymphocytic Leukemia

  • Leukemia (P Wiernik, Section Editor)
  • Published:
Current Treatment Options in Oncology Aims and scope Submit manuscript

Opinion statement

The better understanding of the biology of chronic lymphocytic leukemia (CLL) gained over the past decade has led to the development and introduction of several targeted drugs, with an demonstrable improvement in the prognosis for this currently incurable condition. Currently, Bruton’s tyrosine kinase (BTK) inhibitors, phosphoinositide 3-kinase (PI3K) inhibitors, venetoclax, and CD20 monoclonal antibodies are the key elements in the treatment of both previously untreated and relapsed/refractory CLL patients. Ibrutinib was the first BTK inhibitor approved for clinical use, and showed excellent efficacy and an acceptable safety profile. Following this, the better-tolerated second-generation irreversible BTK inhibitors acalabrutinib and zanubrutinib have been introduced for the treatment of lymphoid malignancies, and acalabrutinib was approved for CLL. When used as single drugs, BTK inhibitors are given continuously until unacceptable toxicity or disease progression; however, when combined with venetoclax and/or CD20 antibodies, they induce deeper response and can be given for a limited time. Recently, promising new reversible BTK inhibitors pirtobrutinib and nemtabrutinib were discovered, and these seem to be more active and better tolerated than their irreversible predecessors. However, they are in an early phase of development and are not currently approved for CLL. The phosphatidylinositol 3-kinase (PI3K) inhibitors idelalisib and duvelisib are highly effective in patients with relapsed CLL, including high-risk disease. The major limitations for their use are adverse events, mostly of autoimmune origin (hepatitis, enteritis/colitis, and pneumonitis). Otherwise, cellular therapies like allogeneic hematopoietic stem cell transplantation and chimeric antigen receptor (CAR) T cells and bispecific monoclonal antibodies offer promise for patients who have failed BTK inhibitors and venetoclax treatment. In the coming years, it is likely that novel targeted therapies will replace immunochemotherapy regimens in most patients.

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Acknowledgments

We thank Edward Lowczowski from the Medical University of Lodz, Poland for editorial assistance.

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Authors and Affiliations

  1. Department of General Hematology, Copernicus Memorial Hospital, Lodz, Poland

    Elżbieta Iskierka-Jażdżewska MD, PhD, Agnieszka Obracaj MD, Marta Urbaniak MD & Tadeusz Robak MD, PhD

  2. Department of Hematology, Medical University of Lodz, Lodz, Poland

    Elżbieta Iskierka-Jażdżewska MD, PhD & Tadeusz Robak MD, PhD

  3. Copernicus Memorial Hospital in Lodz, Ciołkowskiego 2, 93-510, Łódź, Poland

    Tadeusz Robak MD, PhD

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All authors contributed to the manuscript conception. Dr Iskierka-Jażdżewska and Prof. Robak had the idea for the manuscript; Dr Iskierka-Jażdżewska , Dr Urbaniak, and Dr. Obracaj performed the literature search and drafted the manuscript, and Prof. Robak critically revised the work. All authors read and approved the final manuscript.

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Correspondence to Tadeusz Robak MD, PhD.

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Dr Iskierka-Jażdżewska declares that she served as a consultant for Abbvie, AstaZeneca, Sandoz, Novartis and received honoraria and research funding from Roche, Abbvie, AstaZeneca, Sandoz, Takeda, and Regeneron, outside the submitted work, Dr Obracaj and Dr Urbaniak declares that there is no conflict of interest. Prof. Robak declares that he served as a consultant for Janssen, Abbvie, BeiGene, AstaZeneca, Giliad, and Octapharma and received honoraria and research funding from Janssen, Abbvie, BeiGene, AstaZeneca, Octapharma, GSK, Karyopharm, Sanofi, Takeda, and Regeneron, outside the submitted work.

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Iskierka-Jażdżewska, E., Obracaj, A., Urbaniak, M. et al. New Treatment Options for Newly-Diagnosed and Relapsed Chronic Lymphocytic Leukemia. Curr. Treat. Options in Oncol. 23, 775–795 (2022). https://doi.org/10.1007/s11864-022-00974-0

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