International Workshop on CLL

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.

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.

Danielle M. Brander, MD, discusses the primary analysis of the phase 1/2 TRANSCEND CLL 004 trial in patients with relapsed/refractory chronic lymphocytic leukemia or small lymphocytic lymphoma.

Catherine C. Coombs, MD, discusses the feasibility of switching from treatment with a covalent BTK inhibitor to a BCL-2 inhibitor vs a different covalent BTK inhibitor in patients with chronic lymphocytic leukemia or small lymphocytic lymphoma treated in a real-world setting.

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.

Alexey Danilov, MD, PhD, discusses the investigation of BTK degraders in the treatment of chronic lymphocytic leukemia.

Jennifer A Woyach, MD, discusses the prevalence of recurrent genomic alterations in apoptotic machinery in patients with previously treated chronic lymphocytic leukemia who were refractory to B-cell receptor pathway inhibitors.

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.

Jan Joseph Melenhorst, PhD, discusses the evolving understanding of the use of CAR T-cell therapies in the treatment of patients with chronic lymphocytic leukemia.

Mazyar Shadman, MD, MPH, discusses preliminary long-term findings from the evaluation of zanubrutinib in previously treated patients with chronic lymphocytic leukemia or small lymphocytic lymphoma who were intolerant to ibrutinib and/or acalabrutinib.

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.

The presence of at least 1 mutation captured by next-generation sequencing was associated with a shorter time to first treatment among patients with newly diagnosed chronic lymphocytic leukemia, particularly those with mutations in POT1, ATM, FBXW7, and MYD88 genes.

Treatment with acalabrutinib as monotherapy or in combination with obinutuzumab improved quality-adjusted survival compared with chlorambucil plus obinutuzumab in patients with treatment-naïve chronic lymphocytic leukemia.

Meghan Thompson, MD, discusses the results of the phase 1/2 BRUIN study in patients with Richter transformation.

Tadeusz Robak, MD, PhD, discusses the results of the 7-year follow-up analysis of the phase 3 RESONATE-2 trial in chronic lymphocytic leukemia.

During the XIX International Workshop on Chronic Lymphocytic Leukemia, which occurred virtually 17-20 September, Dr. John Byrd was presented the Binet-Rai Medal Award for his outstanding findings, which led to the use of BTK Inhibitors in almost every phase of CLL therapy.

The triplet combination of umbralisib, ublituximab, and pembrolizumab demonstrated durable responses with a tolerable safety profile in patients with relapsed/refractory chronic lymphocytic leukemia and Richter’s transformation.

William G. Wierda, MD, PhD, discusses the fixed-duration cohort results of the phase 2 CAPTIVATE trial in chronic lymphocytic leukemia.

Sikander Ailawadhi, MD, discusses the results of a first-in-human, early phase 1 study of lisaftoclax in patients with hematologic malignancies.

A genome-wide look into changes in three-dimensional chromatin organization between ibrutinib-resistant and parental chronic lymphocytic leukemia cells illustrated the involvement of PAK1 as an oncogenic driver in CLL.

Zanubrutinib monotherapy showed a deepening of response in patients with relapsed/refractory chronic lymphocytic leukemia.

TG-1701, a covalently bound BTK inhibitor, used as monotherapy or in combination with umbralisib and ublituximab, demonstrated promising activity and a manageable safety profile in patients with chronic lymphocytic leukemia.

Lisocabtagene maraleucel in combination with ibrutinib was associated with manageable safety for patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma, according to updated data from the phase 1 TRANSCEND-CLL-004 trial.

Chan Cheah, MBBS, discusses the results of a study evaluating the efficacy and safety of TG-1701 alone and in combination with ublituximab and umbralisib in chronic lymphocytic leukemia.