Meta-Analysis Highlights Promising Efficacy, Safety of Approved CAR T-Cell Products

Researchers found the 3 treatments—axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel (liso-cel)—showed promising efficacy and safety results across histological types, although they noted a need for more real-world data to validate the efficacy of liso-cel.

With multiple chimeric antigen receptor (CAR) T-cell treatments on the market, researchers have begun collecting real-world data on the efficacy and safety of these treatments as they continue to be administered in a broader group of patients than those included in trials on which approvals were based. In a meta-analysis of available data, one group of researchers published their insights on the 3 approved products for large B-cell lymphoma.

Researchers found that the 3 treatments—axicabtagene ciloleucel (axi-cel), tisagenlecleucel (tisa-cel), and lisocabtagene maraleucel (liso-cel)—showed promising efficacy and safety results across histological types, although they noted a need for more real-world data to validate the efficacy of liso-cel, which was just recently approved this year.

“Meta-analysis and systematic reviews on the safety and efficacy of CAR-T cell therapy for hematologic and solid malignancies have been published, but a comprehensive evaluation of the 3 currently marketed CAR-T cell products is lacking,” explained the researchers.

“In real-world clinical setting, most patients receive only these approved products rather than the experimental CAR-T cells that were mainly focused in the previous studies. In addition, the pivotal trials that supported the approval of the 3 CAR-T cell products were limited by the strict inclusion and exclusion criteria, and therefore the characteristics of the study patients were different from those in the real-world,” they said.

Over 2000 patients from 33 studies were analyzed. These patients included those with large B-cell lymphoma, in addition to those with other hematologic malignancies such as follicular lymphoma (FL), acute lymphoblastic leukemia, chronic lymphocytic leukemia, and multiple myeloma.

The treatments demonstrated overall response rates of at least 70%, with more than half of patients achieving a complete response. Compared with tisa-cel, axi-cel yielded improved efficacy for all patients with lymphoma, with the exception of patients with transformedFL/FL. However, the researchers cautioned that comparisons should be determined by randomized controlled trials due to the heterogeneity of patients resulting from different studies.

According to the researchers, their analysis confirmed trial findings that patients treated with axi-cel are at an increased risk of neurotoxicity. Consistent with pivotal trials, the real-world data showed that axi-cel was associated with a significantly higher rate of severe immune effector cell-associated neurotoxicity syndrome—a well-documented side effect of certain CAR T-cell treatment—than tisa-cel (31% vs 8%). The researchers say this could be attributed to axi-cel’s cluster of differentiation (CD)28 co-stimulation domain.

Patients with leukemia treated with tisa-cel were at a higher risk of cytokine release syndrome (CRS)—another well-documented safety concern associated with certain CAR T-cell treatments.

The researchers suggested medical personnel closely monitor body temperature and various cytokine levels, including interleukin (IL)-6, C-reactive protein, interferon-gamma, and ferritin, in these patients. Early intervention can include tocilizumab, and the researchers noted that corticosteroids and anti-IL-6 therapy do not seem to interfere with the efficacy of CAR T-cells.

Reference: Meng J, Wu X, Sun Z, et al. Efficacy and safety of CAR-T cell products axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel for the treatment of hematologic malignancies: a systematic review and meta-analysis. Front Oncol. Published online July 26, 2021. doi:10.3389/fonc.2021.698607