Chronic Lymphocytic Leukemia

Catherine Coombs, MD discusses the present CLL front-line treatment landscape, addressing considerations like choosing fixed-duration or continuous therapy and variations in first-line approaches based on age and ECOG status.

Catherine C. Coombs, MD, presents data investigating venetoclax-based therapy after Bruton tyrosine kinase inhibitors in chronic lymphocytic leukemia.

Jennifer R. Brown, MD, PhD, discusses the clinical implications of the ALPINE study and highlights a subgroup analysis of acquired mutations in patients with chronic lymphocytic leukemia, demonstrating which mutations were associated with resistance to covalent BTK inhibitors.

Treatment with zanubrutinib conferred a PFS benefit vs bendamustine plus rituximab across most biomarker subgroups of patients with treatment-naive chronic lymphocytic leukemia or small lymphocytic lymphoma without del(17p), according to findings from the phase 3 SEQUOIA trial.

Jennifer A Woyach, MD, discusses the efficacy of pirtobrutinib in patients with chronic lymphocytic leukemia or small lymphocytic lymphoma who progressed on treatment with a covalent BTK inhibitor, including subgroups with or without previous exposure to a BCL2 inhibitor.

Responses on the non-covalent BTK inhibitor pirtobrutinib remained high in patients with relapsed chronic lymphocytic leukemia who expressed frequent baseline BTK mutations, according to a genomic analysis of the phase 1/2 BRUIN trial.

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Paolo Ghia, MD, PhD, full professor, discusses a biomarker subgroup analysis of the phase 3 SEQUOIA trial investigating zanubrutinib vs bendamustine plus rituximab in patients with treatment-naive chronic lymphocytic leukemia or small lymphocytic lymphoma without 17p deletions.

Ibrutinib plus venetoclax, given at a duration determined by minimal residual disease, improved progression-free survival and overall survival vs fludarabine, cyclophosphamide, and rituximab in patients with treatment-naive chronic lymphocytic leukemia.

Venetoclax-based therapy generated durable responses both overall and in the second or third line following covalent BTK inhibitor discontinuation in real-world patients with chronic lymphocytic leukemia or small lymphocytic lymphoma.

Pirtobrutinib continued to showcase clinically meaningful efficacy in heavily pretreated patients with chronic lymphocytic leukemia or small lymphocytic lymphoma who had prior exposure to a covalent BTK inhibitor.

Zanubrutinib continued to demonstrate improved progression-free survival benefit over ibrutinib in the treatment of patients with relapsed/refractory chronic lymphocytic leukemia and small lymphocytic lymphoma, according to extended follow-up data from the phase 3 ALPINE trial.

The FDA has granted an accelerated approval to pirtobrutinib for the treatment of adult patients with chronic lymphocytic leukemia or small lymphocytic lymphoma who have received at least two prior lines of therapy, including a BTK inhibitor and a BCL2 inhibitor.

John N. Allan, MD, discusses the importance of understanding fixed-duration treatment approaches with BTK inhibitors and BCL2 inhibitors in patients with chronic lymphocytic leukemia, highlighting data within this treatment armamentarium.

Nicole Lamanna, MD, discusses how the use of novel agents could address resistance associated with current treatment options for patients with chronic lymphocytic leukemia.

John N. Allan, MD, discusses current data detailing the activity of venetoclax-based, fixed-duration regimens in the frontline setting for patients with chronic lymphocytic leukemia; the synergy and promising efficacy signals seen with BCL-2 and BTK inhibitor combinations; and ongoing research efforts exploring triplet regimens vs other continuous approaches in this space.

Nicole Lamanna, MD, discusses the challenges of resistance in patients with CLL, highlights treatment being developed for patients who progress on BTK inhibitor– or venetoclax-based regimens, and emphasizes the need for further enrollment onto clinical trials.

Bhagirathbhai Dholaria, MBBS, discusses limitations in the current CLL standards of care that necessitate more effective therapies; BTK inhibitors and degraders on the horizon for this population; and the potential future role of CAR T-cell therapy for patients with CLL.

The FDA has granted priority review to the supplemental biologics license application seeking approval to expand the indication of lisocabtagene maraleucel to include patients with chronic lymphocytic leukemia or small lymphocytic lymphoma who had prior exposure to a BTK inhibitor and a BCL-2 inhibitor.

Nicole Lamanna, MD, discusses treatment options for patients with chronic lymphocytic leukemia who develop resistance to a prior treatment.

Along with the combination of venetoclax and obinutuzumab, the BTK inhibitor–based regimens of zanubrutinib monotherapy and acalabrutinib plus obinutuzumab represent the preferred options in the National Comprehensive Cancer Network Guidelines for the first-line treatment of patients with chronic lymphocytic leukemia without 17p deletions or TP53 mutations.

The FDA has placed a partial clinical hold on the phase 1 NX-2127-001 trial investigating the novel BTK degrader NX-2127 in patients with relapsed/refractory B-cell malignancies.

Catherine C. Coombs, MD, discusses a real-world investigation of switching to a BCL-2 inhibitor-based regimen vs another covalent BTK inhibitor in patients with chronic lymphocytic leukemia/small lymphocytic leukemia who were intolerant to a prior covalent BTK inhibitor and highlighted factors to consider when deciding between these 2 approaches for this patient population.

Jennifer A. Woyach, MD, elucidates the updated results generated from a phase 2 study of venetoclax monotherapy in patients with relapsed/refractory chronic lymphocytic leukemia (CLL) whose disease progressed on a prior B-cell receptor inhibitor, expanded on key findings from a genomic analysis from the study, and highlighted what these findings could mean for the CLL treatment paradigm.

The United Kingdom’s National Institute for Health and Care Excellence has issued a final draft guidance recommending the approval of zanubrutinib for the treatment of adult patients with untreated, high-risk chronic lymphocytic leukemia harboring a 17p deletion or TP53 mutation.