With the clinical application of CAR-T in China, the combination of ASCT and CART therapy (ASCT-CART) has been explored to improve patients' response and long‐term survival [13–16]. Based on this, some articles have reported on the efficacy of ASCT + CAR-T compared to CAR-T in patients with r/r LBCL and central nervous system. Study results indicate that ASCT + CAR-T demonstrates longer PFS and OS compared to CAR-T [17–18]. Our study utilized real-world data to perform an economic evaluation of CAR-T therapy versus ASCT + CAR-T therapy. All parameters utilized in this investigation were derived from real-world data sources, thereby providing insights into the practical application of CAR-T and ASCT + CAR-T therapies among Chinese patients. This study represents the pioneering effort in China to present findings on patient expenditures alongside the clinical effectiveness of different CAR-T modalities. CAR-T therapy first entered the Chinese market in 2019, offering more treatment options for r/r LBCL patients. Currently, the commercially available CAR-T therapies approved by the China National Medical Products Administration were all based on single-arm clinical trials.
Our study is the first study that includes all available CAR-T formulations (axi-cel, relma-cel, in-hospital) up to September 30, 2022, for r/r LBCL patients in real-world settings. The study results indicate that patients treated with ASCT + CAR-T achieved significantly higher clinical responses while incurred overall higher costs, notably in nursing and medication expenses compared to the CAR-T group. This is primarily due to the necessary expenditures associated with ASCT. It implies that to some extent, the use of ASCT + CAR-T therapy will increase the nursing burden within the healthcare system. From a clinical effectiveness perspective at 6 months post treatment, ASCT + CAR-T demonstrates superior CR (ASCT + CAR-T vs CAR-T: 58.02% vs 44.74%) and ORR (ASCT + CAR-T vs CAR-T: 80.25% vs 60.53%) outcomes irrespective of whether commercial CAR-T is utilized.ASCT + CAR-T therapy was comparatively more expensive (ASCT + CAR-T Vs CAR-T: ¥321,649.84 vs ¥242,265.45) but patients may be willing to pay a higher treatment cost to receive ASCT + CAR-T Therapy.
Additionally, it's worth noting that our study findings indicate that the average cost associated with CAR-T therapy is not notably high. This is primarily because most included patients received in-hospital CAR-T therapy rather than commercial CAR-T, resulting in lower average costs.
Based on our subgroup analysis results, commercial CAR-T yielded higher CR rates compared to in-hospital CAR-T with significant higher treatment cost. After balancing for patient baseline characteristics, we speculate that the difference in efficacy between the two groups may stem from variations in CAR-T manufacturing processes. Commercial CAR-T undergoes stringent production pathways and quality control standards, whereas in-hospital CAR-T formulations may lack standardized quality control, potentially resulting in lower product quality and instability. Despite the inferior manufacturing process and lack of strict quality control associated with in-hospital CAR-T, its lower cost makes it a viable treatment option for many patients. Our study data shows that there was a total of 157 patients treated with CAR-T, but only 10 received commercial CAR-T treatment. This indicates a high demand for CAR-T therapy among patients, but its accessibility is greatly limited due to the high cost. Therefore, in-hospital CAR-T formulations have become one of the treatment choices for patients. Apart from the high treatment costs, the number of patients using commercial CAR-T is extremely limited may also be attributed to the lack of reimbursement by medical insurance for CAR-T therapy. Although more and more commercial CAR-T products are currently available in China, the inability to be reimbursed by medical insurance results in poor accessibility for patients. The low accessibility of CAR-T therapy for Chinese patients due to excessively high treatment costs is currently an unmet need. Improving patient accessibility is a future direction that requires joint efforts from companies and Chinese healthcare insurance.
Our study is limited by a small sample size, which tends to yield more false negative findings, i.e., no difference between the tested groups. However, our research was conducted at a tertiary hospital, aligning with the standards of hospitals in China providing CAR-T therapy. Thus, the favorable effectiveness of CAR-T treatment and its lower incidence of grade III or IV cytokine release syndrome observed in our study confirm CAR-T therapy in addressing urgent unmet medical needs for with relapsed/refractory large B-cell lymphoma. Furthermore, our research encompasses sequential therapy involving ASCT + CAR-T, aiming to support broader clinical options and their application. For future real-world CAR-T therapy studies in China, conducting multicenter research is recommended to acquire more comprehensive sample sizes. Additionally, considering the long-term clinical benefits associated with CAR-T therapy, longer-term observations are necessary to ascertain its extended-term value.