Predictors of Apheresis Product Quality and Impact on Clinical Outcomes in Chimeric Antigen Receptor T-Cell Therapy for R/R DLBCL and B-ALL
Authors: Lee Soo Jung , Jekarl Dong Wook , Eom Ki-Seong , Yoon Jae-Ho 
Published: December 2024

Introduction: Chimeric antigen receptor T-cell (CAR-T) therapy has shown efficacy in relapsed/refractory (r/r) diffuse large B-cell lymphoma (DLBCL) and B-lymphoblastic leukemia (B-ALL) in both clinical and real-world evidence studies. This study aimed to identify predictors of apheresis product quality in patients treated with tisagenlecleucel and evaluate their clinical impact.

Methods: We retrospectively analyzed data from 97 lymphocyte collections performed on 89 South Korean patients undergoing leukapheresis for tisagenlecleucel therapy. Apheresis products were evaluated for total nucleated cell (TNC) and CD3+ T cell counts. Patients with DLBCL (n=67) and B-ALL (n=22) were analyzed. DLBCL patients had a median age of 61 years (range 20-83), while B-ALL patients were younger at 15 years (range 2-25). Male to female ratios were 1.1 and 1.72 for DLBCL and B-ALL, respectively. Hematopoietic cell transplantation (HSCT) rates were 28.3% and 73.7% for DLBCL and B-ALL. Median time from diagnosis to collection was similar, with 28.5 months (range 4.6-194.7) for DLBCL and 26.6 months (range 2.4-149.1) for B-ALL.

Results: Seventy-seven collections resulted in normal products that were transferred into final CAR-T cell products, while 22 were atypical apheresis products terminated at cell collection stage with no advance to CAR-T cell production. Rejected apheresis products were due to 11 clinical deaths, 6 cases of insufficient T cell proliferation, and 3 incidents of microbial contamination. For DLBCL, the collections showed a TNC yield of 20.7 x 109 (5.2-47.2) with 10.7 x 109 (2.1-60.2) CD3+ T cells. For B-ALL, the collections showed a median TNC yield of 11.3 x 109 (3.8-78.5) with 8.0 x 109 (1.1-89.3) CD3+ T cells. Post-tisagenlecleucel relapse rate was 15.1%, and the mortality rate was 30.2% with 18.9% non-relapse mortality rate for DLBCL. For B-ALL, the relapse rate was 15.8% and the mortality rate was 36.8% with 21.1% non-relapse mortality rate.

Baseline characteristics of patients influenced collection results. The absolute lymphocyte count (ALC) at before collection positively correlated with TNC yield in both DLBCL (r=0.539) and B-ALL (r=0.569). In DLBCL, ALC also predicted higher CD3+ T cell yield (r=0.598). Patients with normal BMI had significantly higher CD3+ T cell yields in DLBCL (p=0.048). Prior HSCT in DLBCL patients was associated with higher ALC and TNC values (p=0.033, p=0.011). Atypical products in DLBCL were associated with lower baseline platelets and hematocrit (p=0.001, p=0.043). Atypical products also showed significantly low ALC and CD3+ T cell yield (p=0.002, p&lt;0.001) than the normal pheresis products. In B-ALL, low pre-apheresis ALC (p=0.044) was associated with post-CAR-T relapse (p=0.044). In the survival analysis, apheresis products with higher TNC and CD3+ yields were significantly associated with improved survival in B-ALL patients after CAR-T therapy (p=0.035 and p=0.028, respectively).

Conclusions: ALC is a strong predictor TNC and CD3+ T cell yields in apheresis products, consistent with previous findings. BMI may influence T cell fitness in apheresis collection. Transplantation status was associated with higher ALC and TNC values, likely due to immune reconstitution effects. Baseline hematological parameters serve as decisive factors in determining the success of CAR-T cell manufacturing. In B-ALL patients, pre-apheresis blood status and post-collection product metrics impacted prognosis and survival, indicating that better product metrics correlate with improved treatment outcomes. These findings highlight the interplay between patient factors, apheresis product characteristics, and clinical outcomes in CAR-T cell therapy, and suggest potential strategies for optimizing patient selection.