Chimeric antigen receptor T-cell (CAR-T) therapies are a paradigm-shifting therapeutic in patients with hematological malignancies. However, some concerns remain that they may cause serious cardiovascular adverse events (AEs), for which data are scarce. In this study, gradient boosting machine algorithm-based model was fitted to identify safety signals of serious cardiovascular AEs reported for tisagenlecleucel in the World Health Organization Vigibase up until February 2024. Input dataset, comprised of positive and negative controls of tisagenlecleucel based on its labeling information and literature search, was used to train the model. Then, we implemented the model to calculate the predicted probability of serious cardiovascular AEs defined by preferred terms included in the important medical event list from European Medicine Agency. There were 467 distinct AEs from 3,280 safety cases reports for tisagenlecleucel, of which 363 (77.7%) were classified as positive controls, 66 (14.2%) as negative controls, and 37 (7.9%) as unknown AEs. The prediction model had area under the receiver operating characteristic curve of 0.76 in the test dataset application. Of the unknown AEs, six cardiovascular AEs were predicted as the safety signals: bradycardia (predicted probability 0.99), pleural effusion (0.98), pulseless electrical activity (0.89), cardiotoxicity (0.83), cardio-respiratory arrest (0.69), and acute myocardial infarction (0.58). Our findings underscore vigilant monitoring of acute cardiotoxicities with tisagenlecleucel therapy.

Aim: To perform a cost-effectiveness analysis comparing axicabtagene ciloleucel (axi-cel) with standard of care (SoC; salvage chemoimmunotherapy, followed by high-dose therapy with autologous stem cell rescue for responders) for second-line (2L) treatment of adults with relapsed or refractory large B-cell lymphoma (r/r LBCL) in the pivotal ZUMA-7 trial data from a Japanese payer perspective. Materials & methods: A three-state partitioned survival model was utilized using population and clinical inputs from the ZUMA-7 trial data over a lifetime horizon. Results: Axi-cel was associated with greater incremental quality-adjusted life-years (2.06) and higher incremental total costs ($48,685.59/¥6.9 million) leading to an incremental cost-effectiveness ratio of $23,590.34/¥3.3 million per quality-adjusted life-years compared with SoC. Conclusion: Axi-cel is a cost-effective treatment alternative to SoC for 2L treatment of adults with r/r LBCL.
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Background Chimeric antigen receptor T-cell (CAR-T) therapy has emerged as a promising immunotherapy for various malignancies. However, its use is associated with challenges, including cytokine release syndrome (CRS), a potentially severe complication. This retrospective study aims to analyze the risks, outcomes, and healthcare burden of CRS in patients undergoing CAR-T therapy. Method Data from the 2020 National Inpatient Sample (NIS) were utilized, comprising 415 CAR-T-related hospitalizations. They were categorized into those with CRS (n = 68) and those without CRS (n = 347). Baseline characteristics, including age, gender, race, income, insurance status, and comorbidities, were compared. Outcomes of interest included in-hospital mortality, length of stay (LOS), total hospital charges, and access to complications, associations, and interventions. Statistical analyses, including multivariable models, were employed to assess associations. Results Hospitalizations with CRS did not exhibit significant differences in age, gender, race, income, or insurance status compared to those without CRS. The multivariable analysis showed no statistically significant difference in mortality (adjusted odds ratio (aOR) = 2.48, 95% confidence interval (CI): 0.71 to 8.69, p = 0.151), LOS (coefficient = -2.1 days, 95% CI: -5.43 to 1.21, p = 0.207), or total hospital charges (coefficient = $207,456, 95% CI: $6119 to $421,031, p = 0.057) between the two groups. The CRS group had a higher incidence of fever (aOR = 1.91, 95% CI: 1.15 to 3.17, p = 0.014), acute respiratory failure (aOR = 2.10, 95% CI: 1.01 to 4.40, p= 0.049), and the need for intubation/mechanical ventilation (aOR = 2.59, 95% CI: 1.14 to 5.88, p = 0.024). Hemophagocytic lymphohistiocytosis (HLH) was significantly associated with CRS (aOR = 6.72, 95% CI: 2.03 to 22.18, p = 0.002). Conclusion While the development of CRS in CAR-T-treated patients did not significantly increase mortality, LOS, or total hospital charges, it was associated with specific risks and outcomes, including fever, respiratory failure, and HLH. This study emphasizes the importance of vigilance in recognizing and managing CRS in CAR-T therapy to optimize patient outcomes. The findings contribute valuable insights to guide clinical decision-making in the context of CAR-T therapy.

Autologous hematopoietic stem cell transplantation (ASCT) and chimeric antigen receptor T-cell therapy (CART) are salvage therapies that are utilised for treatment of relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL). However, whether the combination therapy of ASCT and CART (ASCT-CART) can improve the survival of R/R DLBCL remains unknown. Overall, 67 R/R DLBCL patients were included, among which 21 patients underwent ASCT-CART therapy and 46 patients underwent ASCT therapy. The median number of mononuclear cells numbers that were infused in the ASCT-CART and ASCT groups was 4.71 × 108 /kg and 5.36 × 108 /kg, respectively (p = 0.469). The median number of CD34+ cell numbers that were infused in the ASCT-CART and ASCT groups was 2.41 × 106 /kg and 3.05 × 106 /kg, respectively (p = 0.663). The median number of CART cells that were infused was 2.63 × 106 /kg with a median transduction rate of 59.83%. The objective response rates to ASCT-CART and ASCT therapy were 90% and 89%, respectively (p = 1.000). However, the ASCT-CART group showed higher complete remission (CR) rates than the ASCT group (71% vs. 33%; p = 0.003). The ASCT-CART group demonstrated superior 3 year progression-free survival (PFS) (80% vs. 44%; p = 0.036) and lower 3 year relapse/progression rate (15% vs. 56%; p = 0.015) compared to the ASCT group. However, the 3 year overall survival results indicated that there were no differences between the two groups (80% vs. 69%; p = 0.545). For R/R DLBCL patients, ASCT-CART therapy is associated with higher CR rate, better PFS, and lower relapse/progression rate. These data support that ASCT-CART therapy can be used as a salvage therapy for R/R DLBCL patients.