Comparable Outcomes of Point-of-Care and Commercial CD19 CAR-T Therapies: A Patient-Matched Analysis in Large B-Cell Lymphoma
Authors: Marcus Ronit , Avigdor Abraham , Greenbaum Uri , Golan Accav Noa , Shem-Tov Noga , Yerushalmi Ronit , Danylesko Ivetta , Jacoby Elad , Nagler Arnon , Shimoni Avichai , Ballweg Annamaria , Deschênes-Simard Xavier , Luttwak Efrat , Shah Gunjan L. , Scordo Michael , Dahi Parastoo B , Perales Miguel Angel , Zuckerman Tsila , Henig Israel , Yehudai-Ofir Dana , Khatib Hazim , Shouval Roni , Beyar Katz Ofrat 
Published: December 2024

Introduction: Point-of-care (POC) chimeric antigen receptor T-cell (CAR-T) therapy offers accessible treatment with a rapid vein-to-vein time. However, the efficacy of POC CAR-T compared to commercial CAR-T products remains uncertain. To address this, we compared an autologous CD19 POC CAR-T product with commercial alternatives in patients with large B-cell lymphoma (LBCL) using a patient-matched analysis.

Methods: This retrospective international multicenter study included patients with large B-cell lymphoma (LBCL) treated with autologous CD19-directed CAR-T who had received at least two prior lines of therapy across three academic centers. The CAR-T products evaluated were two commercial products (Axi-cel and Tisa-cel) and an established POC product, based on CD28 costimulatory domain (NCT02772198, Kedmi et al., JTCT 2022). The commercial products were administered at all centers, while the POC product was used at one center until the commercial product was approved by the regulatory authorities and in specific subsequent cases. Primary outcomes were overall survival (OS) and progression-free survival (PFS) from the time of infusion. Products were compared using an inverse propensity-weighted model based on age, Karnofsky performance status (KPS), LDH levels, primary refractory disease, and transformed lymphoma.

Results: A total of 330 patients were included in the study: 132 received Axi-cel, 104 received Tisa-cel, and 94 received the POC product. Patients treated with POC CAR-T were younger (median age 51 vs. 62 for Axi-cel and 69 for Tisa-cel, p&lt;0.001), had better KPS (KPS≥90: 71% for POC, 48% for Axi-cel, and 50% for Tisa-cel, p=0.001), higher LDH levels (64% for POC vs. 46% for Axi-cel and 45% for Tisa-cel, p=0.015), and higher rates of primary refractory disease (54% for POC vs. 48% for Axi-cel and 36% for Tisa-cel, p=0.024). The vein-to-vein time was significantly shorter for the POC product, with a median of 11 days (IQR 10-11) compared to 38 days (30-46) for Axi-cel and 44 days (38-53) for Tisa-cel (p&lt;0.001). Consequently, only 21% of patients receiving POC required bridging therapy (primarily steroids), compared to 55% and 67% for Axi-cel and Tisa-cel, respectively.

The POC CAR-T product had a favorable toxicity profile. Cytokine release syndrome grade 2 and above were lowest with POC (26%) compared to Axi-cel (52%) and Tisa-cal (37%, p&lt;0.001). Tisa-cel had the lowest rate of Immune effector cell-associated neurotoxicity syndrome grade 2 or above (12%) compared to POC (29%) and Axi-cel (36%, p&lt;0.001).

Median follow-up ranged between 35 to 49 months, depending on the product. Numerically, median OS was longest with Axi-cel at 31 months (95%CI, 20-NR), followed by Tisa-cel at 16 months (13-NR), and POC at 15 months (9-38). In a propensity score matching analysis, the POC product had a comparable OS risk to Axi-cel (HR 1.35 [95% CI 0.87-2.10], p=0.18) and Tisa-cel (HR 1.03 [95% CI 0.69-1.53], p=0.89). Median PFS was numerically higher with Axi-cel at 11 months (7.5-27), followed by Tisa-cel at 3.3 months (2.5-6.6), and POC at 3.0 months (2.0-17). In the propensity score matching analysis, the POC product showed a trend for lower PFS compared to Axi-cel (HR 1.54 [95% CI 1.00-2.37], p=0.051) and was comparable to Tisa-cel (HR 0.71 [95% CI 0.45-1.11], p=0.13).

Conclusion: To our knowledge, this is the first direct comparison of academic anti-CD19 POC CAR-T with commercial products. Our results indicate that POC CAR-T is a safe and effective treatment option for LBCL, providing comparable outcomes to commercial products. The rapid vein-to-vein time of POC CAR-T makes it an attractive option for patients requiring expedited intervention.