Efficacy and Safety of CAR T-Cell Therapy in Non-Hodgkin Lymphoma: A Systematic Review and Meta-Analysis
Authors: Altaf Faryal , Jamil Abdur , Siddique Rimsha , Qureshi Zaheer 
Published: December 2024

INTRODUCTION
Non-Hodgkin lymphomas (NHL) are a heterogeneous group of lymphoproliferative malignancies known for their unpredictability and tendency for extranodal dissemination. Among this group of malignancies, diffuse large B-cell lymphoma (LBCL) and follicular lymphoma are the most common subtypes of NHL. The NHL's resistance to standard chemotherapy has increased in the past decades. Therefore, a growing need for personalized treatment modalities such as chimeric antigen receptor T-cell therapies (CAR-TCT) has developed.
METHODOLOGY
Two independent authors conducted a comprehensive literature search on three databases using a set of keywords combined with Boolean operators. The literature search was carried out on four electronic databases, namely PubMed, Science Direct, Google Scholar, and the Cochrane Library, for all relevant articles published until July 2024 to identify all relevant studies on the use of CAR-TCT in the treatment of NHLs. The efficacy and safety outcomes of the analysis included the overall survival (OS), the event-free survival (EFS), the progression-free survival, the objective response rate (ORR), and the incidence of adverse events (AEs). The outcomes were then pooled using the Review Manager software (RevMan 5.41) and Comprehensive Meta-analysis software version 3.
RESULTS
The online search yielded 532 articles. However, after a detailed assessment based on our screening and eligibility criteria, only eight articles met our inclusion criteria and were thus included in the review. A pooled analysis of the outcomes found that CAR-TCT significantly increased both the OS and the PFS of NHL patients compared to the standard of care chemotherapy (SOC) (HR 0.79; 95% CI [0.63, 1.00] P = 0.05) and (HR 0.46; 95% CI [0.36, 0.58] P &lt; 0.00001). However, the EFS was not statistically different between the NHL patients treated with CAR-T Cell Therapy and those treated with SOC (HR 0.54; 95% CI [0.26, 1.09] P =0.09). Lastly, the single-arm analysis of the ORR found that about 80.1% (95% CI [77%, 84%] p = 0.00) of NHL patients had a response to CAR-TCT. Further analysis to determine the comparative ORR of NHL patients to either CAR-TCT or SOC found no significant difference in the ORR of both groups (MD 19.23%; 95% CI [-11.34%, 49.80%] p=0.22). Safety analysis found that the incidence of grade ≥ 3 adverse events was comparable between patients treated with CAR-T cells and those receiving standard of care (SOC) (OR 1.12; 95% CI [0.42, 3.00] P = 0.82). However, the incidence of neutropenia was increased in those patients receiving CAR-TCT (OR 2.36; 95% CI [0.99, 5.61] P = 0.05). On the other hand, the incidence of thrombocytopenia, anemia, and nausea was significantly reduced in those patients receiving CAR-TCT than those receiving SOC (OR 0.32; 95% CI [0.13, 0.77] p = 0.01), (OR 0.59; 95% CI [0.36, 0.96] P = 0.03) and (OR 0.35; 95% CI [0.15, 0.81] P = 0.01).
CONCLUSION
The pooled analysis shows that CAR-TCT significantly prolongs the OS and PFS of NHL patients with refractory disease. However, CAR-TCT does not considerably prolong disease-free survival. Furthermore, even though NHL patients respond well to CAR-TCT, the ORR to CAR-TCT is comparable to that of SOC. This study found that CAR-TCT has superior efficacy to SOC in NHL patients. In addition to its efficacy, CAR-TCT has a better safety profile and is thus a promising treatment alternative for these patients.