Chronic Lymphocytic Leukemia

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The United Kingdom’s National Institute for Health and Care Excellence has issued a final draft guidance recommending the approval of zanubrutinib for the treatment of adult patients with untreated, high-risk chronic lymphocytic leukemia harboring a 17p deletion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

The phase 3 BRUIN CLL-314 trial evaluating the selective noncovalent BTK inhibitor pirtobrutinib vs the potent covalent BTK inhibitor ibrutinib is currently enrolling patients with chronic lymphocytic leukemia and small lymphocytic lymphoma who previously received treatment with non-BTK inhibitor therapy.

John N. Allan, MD, discusses a planned evaluation of obinutuzumab triplet consolidation therapy for patients with chronic lymphocytic leukemia /small lymphocytic lymphoma who remain minimal residual disease–positive after initial treatment with zanubrutinib and venetoclax .

Adam Kittai, MD, discusses key findings from a matching-adjusted, indirect comparison of acalabrutinib with or without obinutuzumab vs zanubrutinib monotherapy in treatment-naïve chronic lymphocytic leukemia/small lymphocytic lymphoma.

Patients with treatment-naïve chronic lymphocytic leukemia/small lymphocytic leukemia without 17p deletions experienced superior efficacy following treatment with acalabrutinib plus obinutuzumab compared with zanubrutinib monotherapy.

Administration of acalabrutinib to patients with chronic lymphocytic leukemia with or without cardiovascular disorders at baseline results in a numerically decreased incidence of overall treatment-related cardiac toxicities and a comparable safety profile vs comparator CLL therapies such as ibrutinib.

Treatment with single-agent venetoclax led to prolonged disease response in patients with chronic lymphocytic leukemia who had relapsed or become refractory to prior B-cell receptor inhibitors including ibrutinib and idelalisib, according to findings from a phase 2 study.

The undetectable minimal residual disease ate achieved with bendamustine followed by obinutuzumab, acalabrutinib, and venetoclax increased as the regimen was continued as maintenance treatment in patients with relapsed or refractory chronic lymphocytic leukemia.

Treatment with subcutaneous epcoritamab-bysp elicited rapid and durable responses, including an encouraging complete response rate, and manageable safety in high-risk patients with relapsed/refractory chronic lymphocytic leukemia.

Patients with chronic lymphoctyic leukemia treated with pirtobrutinib monotherapy experienced comparable objective response rates regardless of acquired BTK mutation and a decrease or clearance of BTK cysteine 481 clones despite the emergence of non-C481 clones or other less common mutations during or near the time of progression.

Patients with relapsed/refractory chronic lymphocytic leukemia achieved sustained progression-free survival and overall survival benefit after treatment with fixed-duration venetoclax plus rituximab vs bendamustine plus rituximab, according to data from the phase 3 MURANO trial.

Patients with chronic lymphocytic leukemia who experience disease progression during treatment with either covalent or noncovalent BTK inhibitors displayed a higher frequency of BTK mutations in L528W as well as RAS/RAF/MAPK pathway alterations, indicating that these alterations may play a role in the development of BTK inhibitor resistance.

The duration of treatment with the combination of venetoclax and ibrutinib could be guided by both toxicities and minimal residual disease kinetics in previously untreated patients with intermediate-risk chronic lymphocytic leukemia, according to interim results from the phase 2 ERADIC trial.

Stable peripheral disease levels lasting 12 months were reported in patients with treatment-naïve chronic lymphocytic leukemia following 6 years of continuous treatment with ibrutinib.

John Seymour, MBBS, FRACP, PhD, discusses the characteristics of patient subgroups with chronic lymphocytic leukemia who may benefit from curative treatment with fludarabine, cyclophosphamide, and rituximab.

John Seymour, AM, MBBS, FRACP, FAHMS, PhD, discusses the characteristics of patients with CLL who may benefit from FCR, how genetic testing can provide key insights into individual patient disease patterns, and treatment sequencing options after progression on FCR.

Alessandra Ferrajoli, MD, discusses the continued investigation of fixed-duration therapy as a frontline approach for patients with CLL, highlights both the pros and cons of this strategy, and touches on the unanswered questions regarding fixed-duration therapy that ongoing research aims to address.

Alessandra Ferrajoli, MD, discusses the benefits and limitations of utilizing fixed-duration therapy with monoclonal antibodies in the frontline setting for patients with chronic lymphocytic leukemia.

John Seymour, MBBS, FRACP, PhD, discusses the importance of targeted therapy in patients with chronic lymphocytic leukemia.

John Seymour, MBBS, FRACP, PhD, discusses the curative potential of fludarabine, cyclophosphamide, and rituximab in patients with chronic lymphocytic leukemia.

Mazyar Shadman, MD, MPH, discusses the efficacy and safety of zanubrutinib in chronic lymphocytic leukemia, as well as data derived from the agents use which supports the regulatory approval of zanubrutinib in this patient population.

Mazyar Shadman, MD, MPH, discusses the evolution of BTK inhibitors in CLL, highlights how treatment patterns have evolved with the continued emergence of data on ibrutinib, acalabrutinib, and zanubrutinib, and expands on how pirtobrutinib and liso-cel could address unmet needs for this patient population.

The National Medical Products Administration in China has approved acalabrutinib for use in adult patients with chronic lymphocytic leukemia or small lymphocytic lymphoma who have previously received at least 1 therapy.

Prioty Islam, MD, MSc, discusses the current status of the first-generation BTK inhibitor ibrutinib following the FDA approvals of next-generation BTK inhibitors in patients with chronic lymphocytic leukemia and expands on the few instances in the clinic where she may lean toward treatment with ibrutinib instead of the next-generation BTK inhibitors zanubrutinib or acalabrutinib.

Individualized myelofibrosis treatment begins with correctly identifying a patient’s disease subtype and considering their symptoms, from which accurate decisions regarding the use of JAK inhibitors vs radiation vs hypomethylating agents can lead to spleen and symptom burden reductions.

The FDA has granted clearance for a global, registrational, phase 3 study examining lisaftoclax in combination with a BTK inhibitor in patients with relapsed/refractory chronic lymphocytic leukemia or small lymphocytic lymphoma who received prior treatment with a BTK inhibitor.

Prioty Islam, MD, MSc, discusses the impact of the updated safety and efficacy data seen with FDA-approved BTK inhibitors in patients with chronic lymphocytic leukemia.