Small Molecules in the Treatment of Chronic Lymphocytic Leukemia in 2015 and in the Near Future

Česká verzia

Authors: M. Špaček
Authors place of work: Ústav lékařské biochemie a laboratorní diagnostiky, 1. LF UK a VFN v Praze I. interní klinika – klinika hematologie 1. LF UK a VFN v Praze
Published in the journal: Klin Onkol 2015; 28(Supplementum 3): 45-49
doi: https://doi.org/10.14735/amko20153S45

Summary

Chronic lymphocytic leukemia is one of the most common lymphoid malignancies and is characterized by a highly heterogeneous clinical course. Combined regimens, such as fludarabine, cyclophosphamide, and rituximab have led to improvements in survival in younger patients with chronic lymphocytic leukemia and have become the standard of care in fit patients. However, the majority of chronic lymphocytic leukemia patients are elderly and not all patients are eligible for aggressive chemoimmunotherapy. In addition, patients with poor‑ risk cytogenetics have inferior responses to standard treatments with often shorter durations of response. Furthermore, the treatment outcomes of refractory disease are dismal. Nevertheless, there has been a dramatic change in therapeutic paradigms in the past year. Several new drugs have been approved for the treatment of chronic lymphocytic leukemia, including ibrutinib and idelalisib. These new molecules are orally active agents and both target the B‑ cell receptor associated kinases. Ibrutinib is a selective, irreversible inhibitor of Bruton tyrosine kinase, whereas idelalisib selectively targets phosphatidylinositol‑ 3- kinase (PI3K) δ isoform. These agents have demonstrated remarkable activity in patients with relapsed/ refractory chronic lymphocytic leukemia, as well as patients with high‑risk deletion of the 17p chromosome and/ or TP53 mutation. This review focuses on some of the novel small molecules that are currently approved or in advanced clinical development.

Key words:
chronic lymphocytic leukemia – ibrutinib – idelalisib – rituximab – ABT‑ 199

This study was supported by funds from the elementary science program PRVOUK P27/LF1/1.

I declare that, in connection with the above-mentioned contribution, which I am an author, I have a conflict of interest with the typed the following companies: Gilead, Janssen-Cilag and Roche (honoraria for lectures, travel grants).

The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.

Submitted:
28. 7. 2015

Accepted:
2. 8. 2015

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