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  • Chronic lymphocytic leukemia (CLL) is the most common leukemia in the United States and has a median age of diagnosis of 70 years.

  • The diagnosis of CLL can be established by peripheral blood flow cytometry in the majority of the patients.

  • Treatment of patients with CLL has evolved from chemoimmunotherapy (CIT) to targeted therapies. Most patients are currently treated with oral targeted therapies. Oral targeted therapies include Bruton tyrosine kinase inhibitors, B-cell lymphoma 2 (BCL2) inhibitors, and phosphoinositide 3-kinase (PI3K) inhibitors. Randomized studies have shown improved progression-free survival (PFS) and overall survival (OS) with oral targeted therapies compared with CIT in CLL.

  • Targeted therapies approved for first-line CLL include ibrutinib, acalabrutinib +/- obinutuzumab, and venetoclax + obinutuzumab. Ibrutinib and acalabrutinib are intended to be given daily continuously. Venetoclax and obinutuzumab is a time-limited treatment approach of 1-year duration.

  • In relapsed CLL, the combination of venetoclax + rituximab has shown improved PFS and OS compared with bendamustine and rituximab. Additional approved therapies for relapsed CLL include ibrutinib and acalabrutinib. The PI3K inhibitors idelalisib and duvelisib are also approved for patients with relapsed CLL.

  • Richter transformation remains an unmet medical need. ­Outcomes with CIT remains dismal with median survival of less than 1 year. There are emerging data with checkpoint inhibition, use of venetoclax-based combination therapies, and chimeric antigen receptor T-cell therapy


Chronic lymphocytic leukemia (CLL) is a clonal hematopoietic disorder involving expansion of CD5-positive B cells. Chemoimmunotherapy (CIT) has been the standard first-line treatment for patients with CLL.1 In the past several years, novel oral small-molecule therapies have become available, and these have significantly improved the outcomes of patients with CLL.


CLL is the most common leukemia in the Western Hemisphere, accounting for about 25% of all leukemias in the United States. The estimated number of new CLL cases for 2020 was 21,040, with 4060 deaths. CLL is uncommon in the Asian population and accounts for only 2.5% of all leukemias in Japan. The incidence is age related, with an increase from 5.2 per 100,000 persons older than 50 years to 30.4 per 100,000 persons older than 80 years. Population studies have not identified specific occupational or environmental risk factors for developing CLL.2 The risk of CLL is not increased in Asians settled in Western countries, indicating that genetic factors play a part in CLL risk.3 Up to 15% to 20% of patients with CLL have a family member with CLL or a related lymphoproliferative disorder.4 Genome-wide association studies identified several single nucleotide polymorphisms associated with an increased risk of CLL.5,6


Surface Antigen Phenotype

CLL is a clonal B-cell lymphoid leukemia. CLL cells morphologically resemble small mature lymphocytes arrested in an intermediate stage of the B-cell differentiation pathway. The hallmark of CLL cells is that they are ...

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