Ibrutinib Boosts Efficacy of CAR T-Cell Treatment in Patients with Refractory B-NHL

Article

According to researchers, the findings suggest that receiving ibrutinib improves the activity of anti-CD19-CAR T cells.

As some patients with refractory B-cell non-Hodgkin lymphoma (B-NHL) who received chimeric antigen receptor (CAR) T-cell therapy experienced efficacy shortcomings, researchers studied whether using the treatment a second time, following ibrutinib, may salvage treatment. They found that adding the Bruton's tyrosine kinase (BTK) inhibitor to CAR T-cell therapy improved efficacy.

Following their second CAR-T cell treatment, 6 of 7 patients achieved a complete response (CR) and 1 patient achieved partial remission (PR). According to the researchers, findings suggest that receiving ibrutinib improves the activity of anti-CD19-CAR T cells.

“Multiple preclinical and clinical studies have proven that ibrutinib could improve anti-CD19-CAR T-cell therapy in chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL), but clinical studies on the effect of ibrutinib treatment on the efficacy of 2 anti-CD19-CAR T-cell treatments in the same patients are limited,” wrote the researchers.

Their findings, published in Cancer Science, were based on results from 3 patients with refractory MCL and 4 patients with refractory follicular lymphoma (FL). Each of these patients demonstrated stable disease (SD), PR, or progressive disease (PD) following their first treatment with CAR T-cell therapy.

Patients received ibrutinib as a salvage treatment and maintained SD for at least 7 months following their first treatment with CAR T-cell therapy. When their disease began to progress, they then received their second CAR T-cell treatment.

The researchers noted there were no differences in the transduction efficiency and proliferation between the 2 CAR T-cell treatments, although the second treatment did result in higher peaks of anti-CD19 CAR T-cells, as well as anti-CD19-CAR gene copies.

“Ibrutinib could improve T-cell function by increasing the persistence of activated T-cells, decreasing the Treg/CD4+ T-cell ratio, and diminishing the immune-suppressive properties through BTK-dependent and BTK-independent mechanisms in CLL patients,” explained the researchers. “In addition, inhibition of interleukin (IL)-2-inducible T-cell kinase (ITK) activity would lead to the inhibition of Th2 cell differentiation and promotion of a Th1 cell immune response.”

Assessing the safety impact, researchers found the second CAR T-cell treatment did demonstrate higher grades of cytokine release syndrome, with notable events being grade 0-2 for the first treatment and grades 2-4 the second treatment. There were also more serious hematological toxicities following the second treatment, with grades 1-3 reported after the first treatment and grades 3 and 4 after the second treatment.

Reference:

Liu M, Deng H, Mu J, et al. Ibrutinib improves the efficacy of anti-CD19-CAR T-cell therapy in patients with refractory non-Hodgkin lymphoma. Cancer Sci. Published online May 1, 2021. doi:10.1111/cas.14915

Related Videos
Omar Nadeem, MD, on Initial Efficacy of GPRC5D-CAR in R/R Multiple Myeloma
Omer A. Abdul Hamid, MD, on Improving Gene Therapy’s Effect and Accessibility
George Tachas, PhD, on Tackling DMD Treatment From Multiple Angles
David Suhy, PhD, the cofounder and chief scientific officer of Earli
Deepak L. Bhatt, MD, MPH, MBA, on Incorporating AI into Genetic Research for Cardiovascular Disease
Jeffrey Chamberlain, PhD, on Helping Progress Cell and Gene Therapy Development
Jonathan W. Weinsaft, MD, on Integrating Genetic Research into Cardiovascular Medicine
Jacques Galipeau, MD, on Highlights from ISCT 2024’s Presidential Plenary
Vanee Pho, PhD, the senior director of product management, cell and gene therapy, at Mission Bio
Michael Wang, MD, a professor in the Department of Lymphoma/Myeloma at MD Anderson Cancer Center
© 2024 MJH Life Sciences

All rights reserved.