Clinical Trials and Real-World Data on Brexu-Cel

Video content above is prompted by the following:

Aside from obe-cel’s different design, what are the differences between the dosing and lymphodepletion regimen among brexu-cel, tisa-cel, and obe-cel?

Please comment on obe-cel’s double infusion approach.

Please review the ZUMA-3 trial study design and key data updates with brexu-cel.

Videos

Panelists discuss how the dosing and lymphodepletion regimens of  brexucabtagene autoleucel (brexu-cel),  tisagenlecleucel (tisa-cel), and obecabtagene autoleucel (obe-cel) differ, with insights into obe-cel’s double infusion approach, as well as a deeper dive into the ZUMA-3 trial’s design and data updates with brexu-cel in relapsed/refractory acute lymphoblastic leukemia (R/R ALL).

Introduction to CAR T-Cell Therapies in R/R ALL

We recently had a third CAR T-cell therapy, obe-cel, approved for R/R ALL. Could you introduce the 3 CAR T-cell therapies that are currently available, including their FDA indications, general mechanisms of action, and differences in structure?

Panelists discuss how the recent FDA approval of obecabtagene autoleucel (obe-cel) for relapsed/refractory acute lymphoblastic leukemia (R/R ALL) adds to the existing chimeric antigen receptor (CAR) T-cell therapies, with a focus on the differences in their mechanisms, structures, and FDA indications.

Aaron Logan, MD, PhD, assistant professor of clinical medicine, University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, discusses acalabrutinib (Calquence) in chronic lymphocytic leukemia (CLL).

The development of more selective agents is a general theme that has emerged in novel therapies, says Logan. In many cases, there are off-target toxicities with ibrutinib (Imbruvica), such as atrial fibrillation, and some platelet inhibition, which can lead to bleeding events.

Logan says that a more targeted Bruton's tyrosine kinase (BTK) inhibitor than ibrutinib may have some advantages. The BTK inhibitor acalabrutinib was shown to have a more favorable side effect profile, but it is not yet clear that it is superior to ibrutinib. The role of acalabrutinib has yet to be established, Logan says, but it may be beneficial for patients who cannot tolerate ibrutinib or have contraindications, such as an arrhythmia.

Aaron Logan, MD, PhD, assistant professor of clinical medicine, UCSF Helen Diller Family Comprehensive Cancer Center, discusses acalabrutinib (Calquence) in chronic lymphocytic leukemia.
 

Dr. Logan Discusses Acalabrutinib in CLL

Aaron Logan, MD, PhD, assistant professor of clinical medicine, UCSF Helen Diller Family Comprehensive Cancer Center, discusses the combination of ibrutinib (Imbruvica) and venetoclax (Venclexta) in chronic lymphocytic leukemia (CLL).

Results from the TAP CLARITY study showed that the ibrutinib plus venetoclax elicited a complete response (CR) or CR with incomplete hematologic recovery (CRi) rate of 47% for patients with relapsed/refractory CLL. Patients in the relapsed/refractory cohort achieved minimal residual disease (MRD) negativity after 1 year of combination targeted therapy.

Although the numbers are small, it looks like there are good responses, with all patients eventually developing MRD negativity with the combination of Bruton's tyrosine kinase (BTK) inhibition and BCL-2 inhibition. Logan says that he is not sure this combination will achieve immediate approval because it is not yet clear if the FDA is ready to use MRD as an endpoint for clinical trials.

Aaron Logan, MD, PhD, assistant professor of clinical medicine, UCSF Helen Diller Family Comprehensive Cancer Center, discusses the combination of ibrutinib (Imbruvica) and venetoclax (Venclexta) in chronic lymphocytic leukemia.

Dr. Logan Discusses Ibrutinib Plus Venetoclax in CLL

Aaron Logan, MD, PhD, assistant professor of clinical medicine, UCSF Helen Diller Family Comprehensive Cancer Center, discusses treatment options for patients with chronic lymphocytic leukemia (CLL).

CLL remains the most common leukemia in adults, says Logan. This has led to a lot of innovative therapy, such as monoclonal agents and chemoimmunothearpy.

Additionally, patients with genetic abnormalities such as 17p deletion and 

 now have targeted agents like venetoclax (Venclexta), as these mutations do not respond well to chemoimmunotherapy.

Aaron Logan, MD, PhD, assistant professor of clinical medicine, UCSF Helen Diller Family Comprehensive Cancer Center, discusses treatment options for patients with chronic lymphocytic leukemia.

Aaron Logan, MD, PhD

Articles

Clinical Trials and Real-World Data on Brexu-Cel

Introduction to CAR T-Cell Therapies in R/R ALL

Dr. Logan Discusses Acalabrutinib in CLL

Dr. Logan Discusses Ibrutinib Plus Venetoclax in CLL

Dr. Logan Discusses Treatment Options in CLL