BTKi bonanza in CLL/SLL: Sorting out the differences

Last Updated: Friday, July 17, 2026

In this commentary on the phase 2 study of orelabrutinib by Xu et al., CLL experts discuss the rationale for ongoing research into BTK inhibitors in CLL and provide a summary table comparing efficacy and toxicity data on covalent BTK inhibitors including ibrutinib, acalabrutinib, zanubrutinib, and orelabrutinib across several selected clinical trials.

American Journal of Hematology

British Journal of Hematology

Repeated COVID-19 vaccination to maximum antibody response yields very low mortality and hospitalisation rates in patients with CLL and MBL

Hematological Oncology

Patients' preferences for chronic lymphocytic leukemia treatment: The CHOICE study

Blood Advances

Factors associated with long-term outcomes of CD19 CAR T-cell therapy for relapsed/refractory CLL

2023 Meeting of the Society of Hematologic Oncology (SOHO)

Outcomes of U.S. military veterans with chronic lymphocytic leukemia (CLL) treated with different first-line treatments from 1998 to 2020.

American Journal of Hematology

Orelabrutinib in relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma patients: Multi-center single-arm, open-label, phase 2 study

FDA.gov

FDA approves zanubrutinib for CLL or SLL

Blood

Efficacy of pirtobrutinib in covalent BTK-inhibitor pre-treated relapsed/refractory CLL/SLL: Additional patients and extended follow-up from the phase 1/2 BRUIN study

European Hematology Association 2022 Congress Abstract

Venetoclax-obinutuzumab for previously untreated chronic lymphocytic leukemia: 5-year results of the randomized CLL14 study

Blood

Updated results from a multicenter, phase 2 study of acalabrutinib, venetoclax, obinutuzumab (AVO) in a population of previously untreated patients with CLL enriched for high-risk disease

Blood

Genetic markers and front line FCR/BR vs. RVe, GVe and GIVe treatment: Outcome results from the CLL13/GAIA trial

Chronic Lymphocytic Leukemia Resource Center

BTKi bonanza in CLL/SLL: Sorting out the differences

British Journal of Hematology

Repeated COVID-19 vaccination to maximum antibody response yields very low mortality and hospitalisation rates in patients with CLL and MBL

Hematological Oncology

Patients' preferences for chronic lymphocytic leukemia treatment: The CHOICE study

Blood Advances

Factors associated with long-term outcomes of CD19 CAR T-cell therapy for relapsed/refractory CLL

2023 Meeting of the Society of Hematologic Oncology (SOHO)

Outcomes of U.S. military veterans with chronic lymphocytic leukemia (CLL) treated with different first-line treatments from 1998 to 2020.

American Journal of Hematology

Orelabrutinib in relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma patients: Multi-center single-arm, open-label, phase 2 study

FDA.gov

FDA approves zanubrutinib for CLL or SLL

Blood

Efficacy of pirtobrutinib in covalent BTK-inhibitor pre-treated relapsed/refractory CLL/SLL: Additional patients and extended follow-up from the phase 1/2 BRUIN study

European Hematology Association 2022 Congress Abstract

Venetoclax-obinutuzumab for previously untreated chronic lymphocytic leukemia: 5-year results of the randomized CLL14 study

Blood

Updated results from a multicenter, phase 2 study of acalabrutinib, venetoclax, obinutuzumab (AVO) in a population of previously untreated patients with CLL enriched for high-risk disease

Blood

Genetic markers and front line FCR/BR vs. RVe, GVe and GIVe treatment: Outcome results from the CLL13/GAIA trial

“Double-Refractory” CLL: Progressive Disease after Therapy With Both a BTK Inhibitor and a BCL2 Inhibitor

Management of Atrial Fibrillation in Patients With CLL on BTK Inhibitors

The Importance of Shared Decision-Making in the Frontline Setting