Targeting of B-cell receptor signalling in B-cell malignancies
M Jerkeman1, M Hallek2, M Dreyling3
1Department of Oncology, Lund University, Lund, Sweden.
Journal of Internal Medicine
|March 16, 2017
Summary
Targeted therapies inhibiting the B-cell receptor (BCR) pathway, such as Bruton tyrosine kinase (BTK) and phosphatidylinositol 3-kinase (PI3K) inhibitors, show promise for B-cell malignancies. Careful evaluation of novel combinations is crucial due to observed toxicities.
Area of Science:
- Oncology
- Pharmacology
- Immunology
Background:
- B-cell receptor (BCR) pathway inhibitors are crucial for treating B-cell malignancies.
- Approved agents include ibrutinib (BTK inhibitor) and idelalisib (PI3Kδ inhibitor).
- These drugs are used for chronic lymphatic leukemia (CLL), mantle cell lymphoma (MCL), and Waldenström's macroglobulinemia.
Purpose of the Study:
- To review the efficacy and safety of BCR pathway inhibitors.
- To discuss novel combinations and their potential risks and benefits.
- To explore the future role of BCR inhibitors in B-cell malignancies.
Main Methods:
- Review of existing clinical trial data and published literature.
- Analysis of efficacy and safety profiles of approved and investigational BCR inhibitors.
- Discussion of combination therapies with chemotherapy and other agents.
Main Results:
- Ibrutinib and idelalisib are established first-line therapies for specific patient groups in CLL and MCL.
- Investigational use in diffuse large B-cell lymphoma and marginal zone lymphoma is ongoing.
- Unexpected toxicities arise when combining BCR inhibitors with chemotherapy or lenalidomide.
Conclusions:
- BCR pathway inhibitors represent a significant advancement in B-cell malignancy treatment.
- Careful risk-benefit assessment is necessary for novel combination therapies.
- Further research is needed to optimize the use and combinations of these agents for improved patient outcomes.
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