Novel BTK Inhibitor–Based Combination First-Line Treatment of CLL

By: Jenna Carter, PhD
Posted: Tuesday, January 21, 2025

A presentation at the 2024 American Society of Hematology (ASH) Annual Meeting & Exposition (Abstract 1011) reported the safety and efficacy of the combination of the noncovalent Bruton’s tyrosine kinase (BTK) inhibitor pirtobrutinib, the BCL2 inhibitor venetoclax, and the CD20 monoclonal antibody obinutuzumab in previously untreated patients with chronic lymphocytic leukemia (CLL). Nitin Jain, MD, of The University of Texas MD Anderson Cancer Center, Houston, and colleagues conducted imaging and bone marrow assessments to evaluate measurable residual disease (MRD) after treatment. Their findings revealed high rates of undetectable MRD remission, with no apparent differences in adverse events as previously observed.

A total of 74 treatment-naive patients (median age = 64 years) were enrolled in this study. Treatments were administered in cycles, with daily pirtobrutinib (200 mg) administered continuously until the end of cycle 13, obinutuzumab given for six cycles, and venetoclax administered using a standard ramp-up that was started on day 1 of cycle 2 to the target dose of 400 mg daily. Next-generation sequencing in both blood and bone marrow was used to assess MRD at the end of cycles 7 and 13. Patients with detectable MRD (≥ 10^-5) in either blood or bone marrow at the end of cycle 13 continued pirtobrutinib and venetoclax treatment for another 12 cycles.

Findings revealed that a total of 47 patients reached cycle 7, and blood and bone marrow analyses revealed undetectable MRD (10^-6 sensitivity) in 28 of 43 patients (65%) and 34 of 43 patients (79%), respectively. At the end of cycle 13, among the 27 patients who reached this timepoint, bone marrow and blood analyses showed undetectable MRD (10^-6 sensitivity) in 22 of 27 patients (81%) and 24 of 27 patients (89%), respectively. Grade 3 or 4 neutropenia and thrombocytopenia were reported in 58% and 18% patients, respectively, and no patients have experienced disease progression or died. Of the 27 participants who completed cycle 13, 24 discontinued all therapy and are in follow-up after treatment.

Disclosure: For full disclosures of the study authors, visit ash.com.

2024 ASH Annual Meeting & Exposition