Chronic Lymphocytic Leukemia

Pathophysiology

Chronic lymphocytic leukemia (CLL) is the most common form of adult leukemia in Western countries and is characterized by malignant expansion of B cells in the blood, marrow, and secondary lymphoid tissues as well as focal aggregates of various-sized lymphocytes throughout the lymphoid tissue.1,2 Disease pathogenesis is driven by continuous B-cell receptor (BCR) signaling, which can be triggered by mutations of BCR components or by antigens in the tissue microenvironment.1-3

Landscape

CLL remains an incurable disease despite advances in management strategies, including novel targeted therapies.4 The advent of oral-targeted drugs (Bruton tyrosine kinase inhibitors, phosphoinositide 3-kinase inhibitors and Bcl-2 inhibitors) has improved treatment outcomes for patients with CLL.5 Nonetheless, some patients prove intolerant or resistant to therapy. Areas of research in CLL include the identification of treatment options for patients who have already received multiple prior regimens, have developed resistance, are frail and elderly, or have poor performance status, comorbidities, or advanced age, which may correlate with poor outcomes.1,6 On the other hand, undetectable minimal residual disease (uMRD) has generally been associated with improvements in survival outcomes in CLL.7 There is a critical need to identify novel treatment options for patients with relapsed or refractory CLL, including additional treatment options with different mechanisms of action and clinical studies that assess MRD. Investigational treatment strategies include, but are not limited to, further targeted therapies and chimeric antigen receptor T cell therapy.1,6,8-11

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The safety and efficacy of the agents and/or uses under investigation have not been established. There is no guarantee that the agents will receive health authority approval or become commercially available in any country for the uses being investigated.

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Clinical trial information is sourced from ClinicalTrials.gov. Information is updated manually as clinical trials are published. The efficacy and safety of the agents and/or uses under investigation have not been established. There is no guarantee that the agents will receive health authority approval or become commercially available in any country for the uses being investigated.

References

  1. Yu E-M, et al. Anticancer Res. 2015;35:5149-5165. PMID: 26408673
  2. Zhang S, Kipps TJ. Annu Rev Pathol. 2014;9:103-118. PMID: 23987584
  3. Burger JA, Chiorazzi, N. Trends Immunol. 2013;34:592-601. PMID: 23928062
  4. Li XL, Zhang CX. Oncol Lett. 2016;12:3051-3054. PMID: 27899962
  5. Brown JR, et al. Am Soc Clin Oncol Educ Book. 2016;35:e387-e398. PMID: 27249745
  6. Jain N, O’Brien S. Blood. 2016;128:2193-2194. PMID: 27811187
  7. Vartanov AR, et al. Blood. 2019;134(suppl_1):4291.
  8. Parikh SA. Blood Cancer J. 2018;8:93. PMID: 30283014
  9. Bair SM, Porter DL. Am J Hematol. 2019;94:S10-S17. PMID: 30861173
  10. Geyer MB, et al. JCI Insight. 2019;5:pii: 122627. PMID: 30938714
  11. Hallek M, et al. Lancet. 2018;391:1524-1537. PMID: 29477250