Over the past decade, advances in our understanding of the pathways underlying chronic lymphocytic leukemia (CLL) have enabled a significant expansion of its treatment landscape, with a move towards chemotherapy-free targeted approaches. Bruton’s tyrosine kinase inhibitors (BTKis), phosphatidylinositol 3-kinase inhibitors (PI3Kis), BCL2 inhibitors and CD20 monoclonal antibody (mAb) therapies are now key elements of the CLL treatment paradigm. Ibrutinib was the first-in-class BTKi, followed by acalabrutinib and zanubrutinib, which both demonstrated improved tolerability in comparison with their predecessor. Now, the reversible BTKis pirtobrutinib and nemtabrutinib are under investigation. BTKis are often used in combination with the BCL2 inhibitor venetoclax and/or anti-CD20 mAbs, such as rituximab or obinutuzumab. The PI3Kis idelalisib and duvelisib are often administered for patients with relapsed CLL or high-risk disease. Studies investigating novel agents in these classes are prolific with the BLC-2 and BCL-XL inhibitor navitoclax, the anti-CD20 mAb ublituximab, and the PI3Kis umbralisib, zandelisib and parsaclisib all under investigation for the treatment of CLL.
Despite these advances in treatment, challenges around acquired resistance and treatment-related adverse events persist, and as such patients often require multiple lines of therapy. For example, idelalisib and duvelisib can cause autoimmune adverse events such as pneumonitis and colitis, and BTKis have been associated with cardiac toxicities. Studies investigating optimal patient selection and treatment sequencing are critical to improving patient outcomes.
This Research Topic aims to collate research contributing towards improving the treatment and management of patients with CLL. Manuscripts on the following topics will be welcomed:
- Novel targeted agents for the treatment of CLL
- Novel combination approaches to the treatment of CLL
- Optimizing treatment sequencing in CLL
- Overcoming drug resistance in CLL
- Reducing and managing treatment-related toxicities in CLL
Please note: manuscripts that are solely based on bioinformatics or computational analysis of public databases without validation (independent cohort or biological validation in vitro or in vivo) are out of scope for this section and will not be accepted as part of this Research Topic.
Over the past decade, advances in our understanding of the pathways underlying chronic lymphocytic leukemia (CLL) have enabled a significant expansion of its treatment landscape, with a move towards chemotherapy-free targeted approaches. Bruton’s tyrosine kinase inhibitors (BTKis), phosphatidylinositol 3-kinase inhibitors (PI3Kis), BCL2 inhibitors and CD20 monoclonal antibody (mAb) therapies are now key elements of the CLL treatment paradigm. Ibrutinib was the first-in-class BTKi, followed by acalabrutinib and zanubrutinib, which both demonstrated improved tolerability in comparison with their predecessor. Now, the reversible BTKis pirtobrutinib and nemtabrutinib are under investigation. BTKis are often used in combination with the BCL2 inhibitor venetoclax and/or anti-CD20 mAbs, such as rituximab or obinutuzumab. The PI3Kis idelalisib and duvelisib are often administered for patients with relapsed CLL or high-risk disease. Studies investigating novel agents in these classes are prolific with the BLC-2 and BCL-XL inhibitor navitoclax, the anti-CD20 mAb ublituximab, and the PI3Kis umbralisib, zandelisib and parsaclisib all under investigation for the treatment of CLL.
Despite these advances in treatment, challenges around acquired resistance and treatment-related adverse events persist, and as such patients often require multiple lines of therapy. For example, idelalisib and duvelisib can cause autoimmune adverse events such as pneumonitis and colitis, and BTKis have been associated with cardiac toxicities. Studies investigating optimal patient selection and treatment sequencing are critical to improving patient outcomes.
This Research Topic aims to collate research contributing towards improving the treatment and management of patients with CLL. Manuscripts on the following topics will be welcomed:
- Novel targeted agents for the treatment of CLL
- Novel combination approaches to the treatment of CLL
- Optimizing treatment sequencing in CLL
- Overcoming drug resistance in CLL
- Reducing and managing treatment-related toxicities in CLL
Please note: manuscripts that are solely based on bioinformatics or computational analysis of public databases without validation (independent cohort or biological validation in vitro or in vivo) are out of scope for this section and will not be accepted as part of this Research Topic.
