Current Treatment of Chronic Lymphocytic Leukemia: The Diminishing Role of Chemoimmunotherapy.

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  • Additional Information
    • Source:
      Publisher: Adis, Springer International Country of Publication: New Zealand NLM ID: 7600076 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1179-1950 (Electronic) Linking ISSN: 00126667 NLM ISO Abbreviation: Drugs Subsets: MEDLINE
    • Publication Information:
      Publication: Auckland : Adis, Springer International
      Original Publication: New York, ADIS Press [etc.]
    • Subject Terms:
      Antineoplastic Agents, Immunological/*therapeutic use ; Leukemia, Lymphocytic, Chronic, B-Cell/*drug therapy; Agammaglobulinaemia Tyrosine Kinase/antagonists & inhibitors ; Antineoplastic Agents/therapeutic use ; Antineoplastic Agents, Immunological/administration & dosage ; Antineoplastic Agents, Immunological/adverse effects ; Antineoplastic Agents, Immunological/pharmacology ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell/pathology ; Phosphoinositide-3 Kinase Inhibitors/therapeutic use ; Proto-Oncogene Proteins/antagonists & inhibitors ; Randomized Controlled Trials as Topic ; Recurrence
    • Abstract:
      In this review, we examine the literature supporting treatment decision making in the front-line and relapsed/refractory settings for patients with chronic lymphocytic leukemia (CLL). In the front-line setting, novel-agent-based approaches, including continuous Bruton tyrosine kinase (BTK) inhibitor-based therapy and time-limited venetoclax with obinutuzumab, have demonstrated survival benefit over chemoimmunotherapy. While novel-agent-based front-line approaches are appropriate for most patients, fludarabine, cyclophosphamide, and rituximab (FCR) remains a consideration for a selected population of young patients with immunoglobulin heavy chain variable region gene (IGHV)-mutated disease because of the possibility of a prolonged remission following FCR. As front-line novel-agent-based approaches have not been compared directly, decision making regarding which novel-agent-based approach to use in the front-line setting is often based on comorbidities and shared decision making. In the relapsed/refractory setting, BTK inhibitors, venetoclax-based therapy, and phosphoinositide 3-kinase (PI3K) inhibitors have demonstrated survival benefit when compared with chemoimmunotherapy regimens. Data to support various treatment sequences are limited, which highlights the need for prospective data to examine the optimal treatment sequence. Finally, we examine therapies with combinations of novel agents, and novel agents in development, including covalent and noncovalent BTK inhibitors, PI3K inhibitors, B-cell lymphoma 2 (BCL2) inhibitors, immunotherapies, and cellular therapies. With effective approved options and new agents in development, the role of chemoimmunotherapy in the management of CLL has diminished.
      (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)
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    • Grant Information:
      P30 CA008748 United States CA NCI NIH HHS
    • Accession Number:
      0 (Antineoplastic Agents)
      0 (Antineoplastic Agents, Immunological)
      0 (Phosphoinositide-3 Kinase Inhibitors)
      0 (Proto-Oncogene Proteins)
      EC 2.7.10.2 (Agammaglobulinaemia Tyrosine Kinase)
    • Publication Date:
      Date Created: 20211221 Date Completed: 20220321 Latest Revision: 20230202
    • Publication Date:
      20240104
    • Accession Number:
      PMC9521791
    • Accession Number:
      10.1007/s40265-021-01657-0
    • Accession Number:
      34932207