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Updated: Mar 22, 2026
Immunoglobulin Gene Sequence Analysis In Chronic Lymphocytic Leukemia: From Patient Material To Sequence Interpretation
Published on: November 26, 2018
[Chronic lymphocytic leukemia]
1Department of Pathophysiology, Niigata University of Pharmacy and Applied Life Sciences.
Abstract:
Currently, several novel drugs are available for chronic lymphocytic leukemia (CLL) in Western countries. Of these drugs, those that inhibit the B-cell receptor (BCR) signaling pathway are the most promising. Ibrutinib inhibits BTK in the BCR pathway and can be administered orally. The results of several clinical trials suggest that ibrutinib is highly effective against relapsed/resistant (RR) and treatment-naïve CLL. Furthermore, ibrutinib shows equivalent efficacy on CLL with the 17p deletion. Idelalisib, which also blocks the BCR pathway, inhibits PIK3delta and induces CLL cell death. Clinical trials have shown outstanding efficacy of idelalisib against RR-CLL, especially when administered with antiCD20 antibodies. This drug is also effective against CLL with the 17p deletion. ABT-199 is another novel drug; it inhibits BCL2 signaling, not the BCR pathway, and can be administered orally. The efficacy of ABT-199 against RR-CLL has been demonstrated in a number of clinical trials. These drugs have only mild toxicity and can be used for patients in poor general condition. Unfortunately, none of these drugs have yet been approved in Japan. Rapid resolution of the 'drug lag' problem is necessary.
Insights
Novel drugs targeting the B-cell receptor (BCR) pathway, like ibrutinib and idelalisib, show high efficacy for chronic lymphocytic leukemia (CLL). These treatments, including BCL2 inhibitor ABT-199, offer mild toxicity but face regulatory delays in Japan.
Area of Science:
- Oncology
- Pharmacology
Context:
- Chronic lymphocytic leukemia (CLL) is a prevalent B-cell malignancy.
- Novel targeted therapies are transforming CLL treatment paradigms.
- Significant disparities exist in drug availability between Western countries and Japan.
Purpose:
- To review the efficacy and safety of novel oral agents for chronic lymphocytic leukemia (CLL).
- To highlight the potential of B-cell receptor (BCR) pathway inhibitors and BCL2 inhibitors in CLL management.
- To address the unmet need for timely drug approval in Japan.
Summary:
- Ibrutinib and idelalisib target the BCR pathway, demonstrating high efficacy in relapsed/refractory (RR) and treatment-naïve CLL, including cases with 17p deletion.
- ABT-199, a BCL2 inhibitor, also shows significant efficacy in RR-CLL.
- These novel agents exhibit favorable toxicity profiles, suitable for patients with poor performance status.
Impact:
- These findings underscore the therapeutic potential of targeted agents in CLL.
- The review emphasizes the need to expedite the approval of these life-saving medications in Japan.
- Addressing the 'drug lag' is crucial for improving patient outcomes globally.
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