Chronic lymphocytic leukemia: 2022 update on diagnostic and therapeutic procedures

• Published in: American journal of hematology Vol. 96; no. 12; pp. 1679 - 1705
• Main Authors: Hallek, Michael, Al‐Sawaf, Othman
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.12.2021; Wiley Subscription Services, Inc
• Subjects: Antineoplastic Agents - therapeutic use; Apoptosis; Biomarkers; Blood; Bruton's tyrosine kinase; CD5 antigen; Cell proliferation; Chemotherapy; Chromosome 17; Chronic lymphocytic leukemia; Clinical trials; Clinical Trials as Topic; Combined Modality Therapy; Diagnosis; Disease Management; Genetic markers; Genetic transformation; Hematology; Humans; Immunotherapy, Adoptive; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell - diagnosis; Leukemia, Lymphocytic, Chronic, B-Cell - genetics; Leukemia, Lymphocytic, Chronic, B-Cell - therapy; Lymphatic leukemia; Lymphocytes; Lymphoma; Mutation; Neoplasm Staging; p53 Protein; Patients; Prognosis; Protein-tyrosine kinase; Risk groups
• ISSN: 0361-8609; 1096-8652
• DOI: 10.1002/ajh.26367

Disease overview Chronic lymphocytic leukemia (CLL) is one of the most frequent types of leukemia. It typically occurs in elderly patients and has a highly variable clinical course. Leukemic transformation is initiated by specific genomic alterations that interfere with the regulation of proliferation and of apoptosis in clonal B‐cells. Diagnosis The diagnosis is established by blood counts, blood smears, and immunophenotyping of circulating B‐lymphocytes, which identify a clonal B‐cell population carrying the CD5 antigen as well as typical B‐cell markers. Prognosis and staging The clinical staging systems provide prognostic information by using the results of physical examination and blood counts. Various biological and genetic markers provide additional prognostic information. Deletions of the short arm of chromosome 17 (del[17p]) and/or mutations of the TP53 gene predict resistance to chemoimmunotherapy and a shorter time to progression with most targeted therapies. The CLL international prognostic index integrates genetic, biological, and clinical variables to identify distinct risk groups of patients with CLL. Therapy Only patients with active or symptomatic disease or with advanced Binet or Rai stages require therapy. When treatment is indicated, several therapeutic options exist: a combination of the B‐cell lymphoma 2 (BCL2) inhibitor venetoclax with obinutuzumab, monotherapy with inhibitors of Bruton tyrosine kinase (BTK) such as ibrutinib and acalabrutinib, or chemoimmunotherapy. At relapse, the initial treatment may be repeated, if the treatment‐free interval exceeds 3 years. If the disease relapses earlier, therapy should be changed using an alternative regimen. Patients with a del(17p) or TP53 mutation are usually resistant to chemotherapy and should, therefore, be treated with targeted agents. Future challenges Combinations of targeted agents are now being investigated to create efficient, potentially curative therapies of CLL with fixed duration. One of the most relevant questions currently addressed in clinical trials is the comparison of monotherapies with BTK inhibitors with fixed duration combination therapies. Moreover, the optimal sequencing of targeted therapies remains to be determined. Alternative therapies are needed for patients with BTK and BCL2 inhibitor double‐refractory disease.