Anti-BCMA CAR T-Cell Expansion and Its Association with Response and Toxicity in Multiple Myeloma

An Endothelial Activation and Stress Index (EASIX) Based Predictive Model for Neurotoxicity and Cytokine Release Syndrome (CRS) after B-Cell Maturation Antigen (BCMA)-Directed Chimeric Antigen Receptor (CAR) T-Cell Therapy for Relapsed/Refractory Multiple Myeloma (RRMM)

Clonal Hematopoiesis Is Associated with Severe Cytokine Release Syndrome in Patients Treated with Chimeric Antigen Receptor T-Cell (CAR-T) Therapy

Rapid Response to Idecabtagene Vicleucel in a Myeloma Patient Refractory to Multiple Prior Lines of Anti-BCMA Directed Therapies

Comparative Efficacy and Safety of Ciltacabtagene Autoleucel and Idecabtagene Vicleucel in Real-World Relapsed/Refractory Multiple Myeloma: A Retrospective Intention-to-Treat Analysis

Age defining immune effector cell associated neurotoxicity syndromes in aggressive large B cell lymphoma patients treated with axicabtagene ciloleucel.

Immunological Predictive Markers of Response to Idecabtagene Vicleucel Therapy in Multiple Myeloma : A Real-World Experience from St Louis Hospital (France)

CAR T-cell therapy for solid tumours

Development and Evaluation of an Optimal Human Single-Chain Variable Fragment-Derived BCMA-Targeted CAR T Cell Vector.

Real-World Treatment Patterns and Outcomes of Chimeric Antigen Receptor T-Cell (CART) and Bispecific T-Cell Engager (BiTE) Therapies in Relapsed/Refractory Multiple Myeloma (RRMM) at the Yale Cancer Center Network (YCCN)

7549 Background: While CART and BiTE have led to unprecedented responses in RRMM, some patients (pts) do not respond or have short-lived responses. Currently no predictive markers exist to identify these pts. This study explored pretreatment T-cell fitness and efficacy/toxicity in RRMM using a novel single-cell secretome analysis. We hypothesized that pretreatment Polyfunctional Strength Index (PSI) may predict efficacy to BCMA-directed T-cell therapies. Methods: We included 14 RRMM pts treated with idecabtagene vicleucel or teclistamab at Yale Cancer Center with ≥6 mos post-treatment follow-up. Peripheral blood prior to treatment was frozen and then PBMC’s thawed for analysis. PSI, a metric for T-cell fitness combining polyfunctional T-cells % with the intensity of secreted cytokines, was obtained using the IsoPlexis’ Single-Cell Secretome Platform. The overall PSI was an average of CD4+ and CD8+ PSIs. Response was assessed by the International Myeloma Working Group criteria and response duration was defined as time from response to disease progression. Responder (R) was defined as ≥very good partial response for ≥6 mos. Non-responder (NR) was defined as stable or progressive disease ≤3 mos. Cytokine release syndrome (CRS) and immune-effector cell associated neurotoxicity syndrome (ICANS) were graded using the American Society for Transplantation & Cellular Therapy system. Statistics were performed with Mann-Whitney U test using GraphPad PRISM v.9. Results: There were 7 pts in R group (2 BiTE & 5 CART) and 7 pts in NR group (3 BiTE & 4 CART). Median follow-up time was 13.5 mos(range, 7-27). Median age at treatment was 64 yrs in R and 63 yrs in NR. Extramedullary disease (EM) was present in 14.3%(n=1) in R and 71.4%(n=5) in NR. High-risk cytogenetics, defined as del17p, t(4;14), t(14;16), t(14;20), 1q gain/amplification and del1p, were seen in 42.9%(n=3) in R and 85.7%(n=6) in NR. Median prior lines of therapy was 6(range, 4-9) in R and 8(range, 4-10) in NR. CRS/ICANS occurred 85.7%(n=6) in R and 28.6%(n=2) in NR. Overall PSI was 184 in R and 91 in NR(p=0.1649). CD4+ PSI was 160 in R and 75 in NR(p=0.1649). CD8+ PSI was 207 in R and 108 in NR(p=0.1981). Overall PSI was 143 in CRS/ICANS and 130 in no CRS/ICANS(p=0.7546). Conclusions: Overall PSI, CD4+ PSI and CD8+ PSI were 1.9-2.1 times higher in R compared to NR and overall PSI was slightly higher in CRS/ICANS compared to no CRS/ICANS though the difference was not statistically significant. One limitation was a small sample size and thus testing PSI in a larger cohort might yield statistically significant results. The NR group had more high-risk cytogenetics and higher EM. One confounder could be that measuring peripheral T-cell fitness may not be sufficient to predict response in EM where spatial determinants of T-cell influx play a role.

Chimeric Antigen Receptor T Cells: Toxicity and Management Considerations

Utilization of Investigations for Neurotoxicity in CD19 and BCMA CART Recipients

Peripheral Blood CAR T-Cell Level Using a Clia-Validated Assay Is Prognostic for Treatment Response and Icans in Large B-Cell Lymphoma

Impact of Daratumumab Refractoriness on Clinical Outcomes Following CAR T-Cell Therapy for Relapsed/Refractory Multiple Myeloma

Absolute Lymphocyte Count As a Predictor of Safety and Efficacy Post CART for Multiple Myeloma and B Cell Malignancies