Chimeric Antigen Receptor T-cell Therapy Research Articles

EphA3 CAR T cells are effective against glioblastoma in preclinical models

BackgroundAdoptive T-cell therapy targeting antigens expressed in glioblastoma has emerged as a potential therapeutic strategy to prevent or delay recurrence and prolong overall survival in this aggressive disease setting. Ephrin...

Comparing the Differences in Adverse Events among Chimeric Antigen Receptor T-Cell Therapies: A Real-World Pharmacovigilance Study.

In this study, we compared the similarities and differences in adverse events (AEs) among CAR T-cell products through signal mining via the FDA Adverse Event Reporting System (FAERS) and identified unknown AEs to provide a reference for safe clinical medication. Data from the FAERS database spanning from the fourth quarter of 2017 to the first quarter of 2024 were extracted. Signals were identified using the reporting odds ratio (ROR) method and the Medicines and Healthcare Products Regulatory Agency (MHRA) method. A total of 11,386 AE reports related to six CAR T-cell products were selected. The top three categories of AEs reported were nervous system disorders, immune system disorders, and general disorders and administration site conditions. However, there were variations in the AE spectra among the different CAR T-cell products. The BCMA-targeting drugs idecabtagene vicleucel (Ide-cel) and ciltacabtagene autoleucel (Cilta-cel) were found to be associated with parkinsonism, which were not observed in CD19-targeting drugs. Tisagenlecleucel (Tisa-cel) and axicabtagene ciloleucel (Axi-cel) exhibited cerebrovascular accident-related AEs, graft versus host disease, and abnormal coagulation indices. Cilta-cel was associated with cerebral hemorrhage, intracranial hemorrhage, cranial nerve disorder, and facial nerve disorder. Cardiopulmonary toxicity, including hypoxia, tachypnoea, cardiorenal syndrome, and hypotension, exhibited strong signal intensities and considerable overlap with CRS. The number of positive signals for cardiopulmonary toxicity associated with drugs targeting CD-19 is greater. Clinicians should assess patients prior to medication and closely monitor their vital signs, mental status, and laboratory parameters during treatment.

Prediction of Response to FDA-Approved Targeted Therapy and Immunotherapy in Acute Lymphoblastic Leukemia (ALL).

Acute lymphoblastic leukemia (ALL) represents the predominant cancer in pediatric populations, though its occurrence in adults is relatively rare. Pre-treatment risk stratification is crucial for predicting prognosis. Important factors for assessment include patient age, white blood cell (WBC) count at diagnosis, extramedullary involvement, immunophenotype, and cytogenetic aberrations. Minimal residual disease (MRD), primarily assessed by flow cytometry following remission, plays a substantial role in guiding management plans. Over the past decade, significant advancements in ALL outcomes have been witnessed. Conventional chemotherapy has remarkably reduced mortality rates; however, its intensive nature raises safety concerns and has led to the emergence of treatment-resistant cases with recurrence of relapses. Consequently, The U.S. Food and Drug Administration (FDA) has approved several novel treatments for relapsed/refractory ALL due to their demonstrated efficacy, as indicated by improved complete remission and survival rates. These treatments include tyrosine kinase inhibitors (TKIs), the anti-CD19 monoclonal antibody blinatumomab, anti-CD22 inotuzumab ozogamicin, anti-CD20 rituximab, and chimeric antigen receptor (CAR) T-cell therapy. Identifying the variables that influence treatment decisions is a pressing necessity for tailoring therapy based on heterogeneous patient characteristics. Key predictive factors identified in various observational studies and clinical trials include prelymphodepletion disease burden, complex genetic abnormalities, and MRD. Furthermore, the development of serious adverse events following treatment could be anticipated through predictive models, allowing for appropriate prophylactic measures to be considered. The ultimate aim is to incorporate the concept of precision medicine in the field of ALL through valid prediction platform to facilitate the selection of the most suitable treatment approach.

Rational combinatorial targeting by adapter CAR-T-cells (AdCAR-T) prevents antigen escape in acute myeloid leukemia

Targeting AML by chimeric antigen receptor T-cells (CAR-T) is challenging due to the promiscuous expression of AML-associated antigens in healthy hematopoiesis and high degree of inter- and intratumoral heterogeneity. Here, we present single-cell expression data of AML-associated antigens in 30 primary pediatric AML samples. We identified CD33, CD38, CD371, IL1RAP and CD123 as the most frequently expressed. Notably, high variability was observed not only across the different patient samples but also among leukemic cells of the same patient suggesting the necessity of multiplexed targeting approaches. To address this need, we utilized our modular Adapter CAR (AdCAR) platform, enabling precise qualitative and quantitative control over CAR-T-cell function. We show highly efficient and target-specific activity for newly generated adapter molecules (AMs) against CD33, CD38, CD123, CD135 and CD371, both in vitro and in vivo. We reveal that inherent intratumoral heterogeneity in antigen expression translates into antigen escape and therapy failure to monotargeted CAR-T therapy. Further, we demonstrate in PDX models that rational combinatorial targeting by AdCAR-T-cells can cure heterogenic disease. In conclusion, we elucidate the clinical relevance of heterogeneity in antigen expression in pediatric AML and present a novel concept for precision immunotherapy by combinatorial targeting utilizing the AdCAR platform.

Long-term neurocognitive effects of chimeric antigen receptor T-cell therapy: Integrating assessments into nursing practice.

Chimeric antigen receptor t-cell (CAR-T) therapy is a newly evolving therapy with well-known acute neurotoxic effects. While the long-term neurotoxic effects of this therapy are under-researched, they exist in subsets of the post-treatment population. Nurses can focus on assessments before and after CAR-T therapy to determine the degree to which these neurotoxic effects progress. These assessments include subjective and objective tools, as well as an understanding of risk factors associated with a higher degree of adverse cognitive events. By utilizing current research, hematological nurses can advocate for this unmet need to be monitored and intervened upon to improve patient outcomes.

Inotuzumab ozogamicin in adult acute lymphoblastic leukemia: Development, current status, and future directions.

Inotuzumab ozogamicin (InO) is an antibody-drug conjugate approved for the treatment of relapsed/refractory B-cell acute lymphoblastic leukemia (ALL). Several clinical trials are investigating InO in combination with low-intensity chemotherapy or other anti-ALL-targeted therapies in the salvage and frontline settings, notably in older adults who often cannot tolerate intensive chemotherapy and tend to have higher-risk disease. InO is also increasingly used to bridge patients to hematopoietic stem cell transplantation (HSCT), in sequence with chimeric antigen receptor T-cell therapy, to eliminate measurable residual disease and to prevent post-HSCT relapse. Veno-occlusive disease/sinusoidal obstruction syndrome is a potential complication of InO treatment, particularly when followed by HSCT. Herein, the authors review the historical development and current status of InO, strategies for mitigating the risk of InO-related veno-occlusive disease/sinusoidal obstruction syndrome, and future directions for InO research and clinical use.

Long-term neurocognitive effects of chimeric antigen receptor T-cell therapy: Integrating assessments into nursing practice

La thérapie par lymphocytes T à récepteur antigénique chimérique (CART) est un traitement récent aux effets neurotoxiques bien connus. Peu de recherches ont étudié les effets neurotoxiques à long terme, bien que certaines données aient été recueillies après le traitement chez quelques sous-ensembles de patients. Pour mesurer la progression des effets neurotoxiques, les infirmières peuvent évaluer l’état neurologique des patients avant et après la thérapie CARTT. Ces évaluations font appel à des outils subjectifs et objectifs, et exigent de bien comprendre les facteurs de risque associés à un degré élevé d’effets cognitifs indésirables. Les infirmières en hématologie peuvent agir pour répondre à ce besoin négligé en appliquant des mesures d’intervention et de suivi qui s’appuient sur la recherche actuelle, ce qui améliorera le devenir des patients. Mots-clés : thérapie par lymphocytes T à récepteur antigénique chimérique, évaluations infirmières, effets neurotoxiques

Optimizing the post-CAR T monitoring period in recipients of axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel

AbstractCD19–directed chimeric antigen receptor T-cell (CAR T) therapies, including axicabtagene ciloleucel (axi-cel), tisagenlecleucel (tisa-cel), and lisocabtagene maraleucel (liso-cel), have transformed the treatment landscape for B-cell non-Hodgkin lymphoma, showcasing significant efficacy but also highlighting toxicity risks such as cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS). The US Food and Drug Administration has mandated patients remain close to the treatment center for 4 weeks as part of a Risk Evaluation and Mitigation Strategy to monitor and manage these toxicities, which, although cautious, may add to cost of care, be burdensome for patients and their families, and present challenges related to patient access and socioeconomic disparities. This retrospective study across 9 centers involving 475 patients infused with axi-cel, tisa-cel, and liso-cel from 2018 to 2023 aimed to assess CRS and ICANS onset and duration, as well as causes of nonrelapse mortality (NRM) in real-world CAR T recipients. Although differences were noted in the incidence and duration of CRS and ICANS between CAR T products, new-onset CRS and ICANS are exceedingly rare after 2 weeks after infusion (0% and 0.7% of patients, respectively). No new cases of CRS occurred after 2 weeks and a single case of new-onset ICANS occurred in the third week after infusion. NRM is driven by ICANS in the early follow-up period (1.1% until day 28) and then by infection through 3 months after infusion (1.2%). This study provides valuable insights into optimizing CAR T therapy monitoring, and our findings may provide a framework to reduce physical and financial constraints for patients.

CD98 heavy chain protein is overexpressed in non-small cell lung cancer and is a potential target for CAR T-cell therapy

Chimeric antigen receptor (CAR) T cells are effective against hematological cancers, but are less effective against solid tumors such as non-small cell lung cancer (NSCLC). One of the reasons is that only a few cell surface targets specific for NSCLC cells have been identified. Here, we report that CD98 heavy chain (hc) protein is overexpressed on the surface of NSCLC cells and is a potential target for CAR T cells against NSCLC. Screening of over 10,000 mAb clones raised against NSCLC cell lines showed that mAb H2A011 bound to NSCLC cells but not normal lung epithelial cells. H2A011 recognized CD98hc. Although CAR T cells derived from H2A011 could not be established presumably due to the high level of H2A011 reactivity in activated T cells, those derived from the anti-CD98hc mAb R8H283, which had been shown to lack reactivity with CD98hc glycoforms expressed on normal hematopoietic cells and some normal tissues, were successfully developed. R8H283 specifically reacted with NSCLC cells in six of 15 patients. R8H283-derived CAR T cells exerted significant anti-tumor effects in a xenograft NSCLC model in vivo. These results suggest that R8H283 CAR T cells may become a new therapeutic tool for NSCLC, although careful testing for off-tumor reactivity should be performed in the future.

Evolving Horizons in Pediatric Leukemia: Novel Insights, Challenges, and the Journey Ahead.

Pediatric leukemia, encompassing acute lymphoblastic leukemia (ALL) and acute myeloid leukemia, remains a formidable challenge despite significant treatment advancements. This review examines recent developments in immunotherapy, chemotherapy, and bone marrow transplantationfor pediatric leukemia through a comprehensive analysis of recent literature, focusing on critical studies and clinical trials. Immunotherapy, including monoclonal antibodies, such as blinatumomab and inotuzumab ozogamicin, and chimeric antigen receptor T-cell therapies, such as tisagenlecleucel and brexucabtagene autoleucel, have demonstrated promising results in relapsed or refractory B-cell ALL (B-ALL), achieving notable remission rates with manageable side effects. Chemotherapy continues to be the primary treatment, utilizing multiphase regimens tailored to individual risk profiles. Bone marrow transplantation, especially allogeneic stem cell transplantation, offers potential cures for high-risk or relapsed cases, though it poses risks including graft-versus-host diseaseand infections. Despite these advancements, treatment resistance, toxicity, and accessibility persist. This review also discusses the long-term outcomes among pediatric leukemia survivors, focusing on late-onset side effects associated with treatments such as chemotherapy and bone marrow transplantation, encompassing secondary malignancies, organ dysfunction, and neurocognitive impacts. Ongoing research and clinical trials are crucial to refine these therapies, enhance their efficacy, and reduce adverse effects, ultimately improving young patients' survival and quality of life.

Time - The fourth dimension of immune cells.

Deciphering the intricate cell-state transitions orchestrating immune adaptation over time stands as a cornerstone for advancing biological understanding. However, the lack of empirical in vivo genomic technologies capable of capturing cellular dynamics has posed a significant challenge. In response to this gap, a groundbreaking study introduces Zman-seq, a single-cell technology that records transcriptomic dynamics across time by incorporating time stamps into circulating immune cells, enabling their tracking in tissues for extended periods. The application of Zman-seq in glioblastoma research has successfully unraveled the cell state and molecular trajectories underlying the dysfunctional immune microenvironment. Understanding the temporal aspects of cell-state transitions during immune responses is pivotal for advancing our knowledge in biology. The emergence of Zman-seq addresses the current limitations in empirical in vivo genomic technologies, offering a revolutionary approach to studying the dynamics of immune cells over time. This highlight comprehensively explores the implications of Zman-seq in resolving cell-state transitions and molecular trajectories within the dysfunctional immune microenvironment in different types of immunotherapy. This technique has particular potential for chimeric antigen receptor T-cell therapy, overriding drug resistance, clinical medication optimization, and facilitating drug development. In particular, this article discusses potential strategies for improving the efficacy of clinical treatments.

Chick Embryo Chorioallantoic Membrane as a Platform for Assessing the InVivo Efficacy of Chimeric Antigen Receptor T-cell Therapy in Solid Tumors.

The fertilized chicken egg chorioallantoic membrane (CAM), a highly vascularized membrane nourishing the developing embryo, also supports rapid growth of three-dimensional vascularized tumors from engrafted cells and tumor explants. Because murine xenograft models suffer limitations of time, cost, and scalability, we propose CAM tumors as a rapid, efficient screening tool for assessing anti-tumor efficacy of chimeric Ag receptor (CAR) T cells against solid tumors. We tested the efficacy of human epidermal growth factor receptor 2 (HER2)-specific CAR T cells against luminescent, HER2-expressing (FaDu, SCC-47) or HER2-negative (MDA-MB-468) CAM-engrafted tumors. Three days after tumor engraftment, HER2-specific CAR T cells were applied to tumors grown on the CAM. Four days post-CAR T cell treatment, HER2-expressing FaDu and SCC-47 tumors treated with CAR T showed reduced viable cancer cells as assessed by luciferase activity. This reduction in viable tumor cells was confirmed by histology, with lower Ki-67 staining observed in CAR T cell-treated tumors relative to T cell-treated controls. Persistence of CAR T in CAM and tumor tissue 4 days post-treatment was confirmed by CD3 staining. Altogether, our findings support further development of the chick CAM as an invivo system for rapid, scalable screening of CAR T cell efficacy against human solid tumors.

Late-onset relapsing neurotoxicity after Brexucabtagene autoleucel associated with high chimeric antigen receptor T cells in cerebrospinal fluid

Background aimsMounting evidence suggests that persistent cell expansion is the main driver for both efficacy and toxicity of chimeric antigen receptor (CAR) T-cell therapy. Hereby, we describe a case of delayed recurrent neurotoxicity associated with late CAR T-cells re-expansion. Case descriptionA 44-year-old man suffering from mantle cell lymphoma received brexu-cel. After infusion, he developed grade 2 cytokine release syndrome. On day +11, grade 3 neurotoxicity was reported and high-dose methylprednisolone was started with a complete resolution of neurological manifestations. On day +30, he experienced a late-onset CAR T-cell toxicity associated with CAR T-cell re-expansion. The patient was treated with tocilizumab and dexamethasone, with resolution of symptoms. On day +58, he was readmitted for new onset of neurotoxicity. Notably, a new CAR T-cell expansion was observed, with an unexpectedly elevated cerebrospinal fluid/blood ratio. The patient was promptly treated with dexamethasone and then escalated to high-dose methylprednisolone and anakinra, with resolution of his neurologic condition noted. ConclusionsCAR T-cell–related neurotoxicity usually has an early monophasic course. To our knowledge, this is the first case of late-onset, recurrent neurotoxicity. Moreover, an elevated level of cerebrospinal fluid CAR T cells was observed, which may suggest that the delayed neurotoxicity was primarily caused by the brain infiltration of CAR T cells rather than driven by cytokine-mediated neuroinflammation.

Comprehensive characterization of cytopenia after chimeric antigen receptor-T cell infusion in patients with relapsed or refractory multiple myeloma

BackgroundMany studies have demonstrated the effectiveness of chimeric antigen receptor-T (CAR-T) cell therapy for relapsed or refractory multiple myeloma (RRMM), but the hematologic toxicity has not been well characterized. MethodsA total of 111 adults with RRMM who received BCMA CAR-T cells, BCMA + CD19 CAR-T cells or tandem BCMA/CD19 dual-target (BC19) CAR-T cells infusion were enrolled. We characterized cytopenia and hematologic recovery at different time points after CAR-T-cell therapy, analyzed the effect of cytopenia on prognosis and identified the risk factors. ResultsPatients had a high probability of cytopenia, with anemia, neutropenia and thrombocytopenia occurring in 92%, 95% and 73%, respectively. There were 60 (54%) patients had prolonged hematologic toxicity (PHT) after D28. The median hemoglobin and platelet count were significantly lower at D28 post-CAR-T cell therapy than at baseline. Hemoglobin increased to above baseline at D90. The median absolute neutrophil count was lower than baseline at D0 and D28, and it recovered to baseline at D180. The baseline level of lactate dehydrogenase was associated with thrombocytopenia. Extramedullary involvement was associated with hemoglobin recovery, while the baseline level of albumin and types of CAR-T were related to platelet recovery. Patients with anemia at baseline and at D0, D180 and D360 had shorter progression-free survival (PFS), while anemia at D0, D60, D180 and D360 was associated with shorter overall survival (OS). Neutropenia at D0 was associated with shorter PFS and patients with neutropenia at D90 or D180 had shorter OS. Patients with thrombocytopenia at any time had shorter PFS and OS. Compared to patients without PHT, patients with PHT had shorter PFS and OS. ConclusionsThe majority of RRMM patients treated with CAR-T cells experienced cytopenia. Cytopenia occurred at specific time points was associated with a poorer prognosis.

Procalcitonin level threshold and antibiotic use in patients receiving chimeric antigen receptor T-cell therapy

ABSTRACT Background: Patients undergoing chimeric antigen receptor (CAR) T-cell therapy are vulnerable to infection and sepsis. Treatment course is frequently complicated by cytokine release syndrome which is often clinically and biochemically indistinguishable from sepsis. Procalcitonin (PCT) levels have been examined as a promising biomarker for infection in this cohort of patients. Methods: In this study, we measured daily PCT levels for patients for fourteen days (or hospital discharge) after receiving CAR T-cells to determine threshold PCT values specific for infection compared to those without infection. Results: We present preliminary results of our enrolled cohort to date (sixteen patients). Infection was present in only 12.5% of patients. However, those diagnosed with sepsis had elevated PCT levels with a peak mean of 2.6 µg/L observed on the seventh day post-treatment compared to those without infection remaining below 0.5 µg/L. Furthermore, we observed a trend for early and liberal antibiotic administration within our cohort. Conclusion: Our study highlights the challenges of antimicrobial stewardship in managing CAR T-cell therapy recipients. Our preliminary results underscore the utility of PCT in the risk-stratification and diagnosis of those patients at high risk for infectious complications after receiving CAR T-cell therapy and continue to advocate for a PCT threshold of 1.5 µg/L for diagnosing sepsis. Additionally, in the setting of CRS and lymphodepletion, where white cell count and CRP value are unreliable, a PCT value of < 0.5 µg/L may help exclude sepsis.

Venous Thromboembolism Risk in Hematological Malignancies Post-Chimeric Antigen Receptor T-Cell (CAR-T) Therapy: A Meta-Analysis of Phase 2 and Phase 3 Clinical Trials.

Chimeric Antigen Receptor T-cell (CAR-T) therapy uses genetically engineered T-cells with specific binding sites. This therapy allows for tumor specificity and durable treatment responses for patients with hematological malignancies. In this review, we study the risk of venous thromboembolism (VTE) associated with CAR-T therapy. We searched the National Institutes of Health library, Cochrane Library Databases, ClinicalTrials.gov database, and medical literature search engines PubMed and Google Scholar for Phase 2 and Phase 3 drug-efficacy and safety trials to determine the aggregate incidence and risk of VTE treated with CAR-T. Of 1127 search results, nine studies were identified and included in our meta-analysis. Of the 1017 patients who received therapy, 805 patients (79.15%) experienced some degree of CRS, and 122 patients (11.9%) experienced severe CRS (higher than grade 3). Only three out of one thousand and seventeen patients were reported to have experienced venous thromboembolism. Our study did not find a statistically significant association between increased VTE incidence (OR = 0.0005, 95% CI [0.0001, 0.0017]) and CRS/ICANS (p < 0.0001). There was a 0.0050 (95% confidence interval [0.0019, 0.0132]) relative risk for VTE. In our study, we did not find a statistically significantly increased risk of developing VTE despite CRS and underlying malignancy, which have been associated with increased risk of VTE.

Prospects of Synergy: Local Interventions and CAR TCell Therapy in Solid Tumors.

Chimeric antigen receptor Tcell therapy has been established in the treatment of various Bcell malignancies. However, translating this therapeutic effect to treat solid tumors has been challenging because of their inter-tumoral as well as intratumoral heterogeneity and immunosuppressive microenvironment. Local interventions, such as surgery, radiotherapy, local ablation, and locoregional drug delivery, can enhance chimeric antigen receptor Tcell therapy in solid tumors by improving tumor infiltration and reducing systemic toxicities. Additionally, ablation and radiotherapy have proven to (re-)activate systemic immune responses via abscopal effects and reprogram the tumor microenvironment on a physical, cellular, and chemical level. This review highlights the potential synergy of the combined approaches to overcome barriers of chimeric antigen receptor Tcell therapy and summarizes recent studies that may pave the way for new treatment regimens.

Molecular mechanisms promoting long-term cytopenia after BCMA CAR-T therapy in multiple myeloma

AbstractHematologic toxicity is a common side effect of chimeric antigen receptor T-cell (CAR-T) therapies, being particularly severe among patients with relapsed or refractory multiple myeloma (MM). In this study, we characterized 48 patients treated with B-cell maturation antigen (BCMA) CAR-T cells to understand kinetics of cytopenia, identify predictive factors, and determine potential mechanisms underlying these toxicities. We observed that overall incidence of cytopenia was 95.7%, and grade >3 thrombocytopenia and neutropenia, 1 month after infusion, was observed in 57% and 53% of the patients, respectively, being still present after 1 year in 4 and 3 patients, respectively. Baseline cytopenia and high peak inflammatory markers were highly correlated with cytopenia that persisted up to 3 months. To determine potential mechanisms underlying cytopenias, we evaluated the paracrine effect of BCMA CAR-T cells on hematopoietic stem and progenitor cell (HSPC) differentiation using an ex vivo myeloid differentiation model. Phenotypic analysis showed that supernatants from activated CAR-T cells (spCAR) halted HSPC differentiation, promoting more immature phenotypes, which could be prevented with a combination of interferon γ, tumor necrosis factor α/β, transforming growth factor β, interleukin-6 (IL-6) and IL-17 inhibitors. Single-cell RNA sequencing demonstrated upregulation of transcription factors associated with early stages of hematopoietic differentiation in the presence of spCAR (GATA2, RUNX1, CEBPA) and a decrease in the activity of key regulons involved in neutrophil and monocytic maturation (ID2 and MAFB). These results suggest that CAR-T activation induces HSPC maturation arrest through paracrine effects and provides potential treatments to mitigate the severity of this toxicity.

Enhancement of CAR-T cell-targeted immune responses against solid tumors: role of lowered CARs affinity and addition of PD-1 chimeric antigen complexes

Cancers rising prevalence demands novel treatments. Chimeric Antigen Receptor T-cell (CAR-T) therapy emerges as a transformative option. Conventional cancer treatments of-ten lack efficacy and carry severe side effects. This study focuses on enhancing CAR-T therapy against solid tumors. Strategies include lowering CAR affinity for antigens and in-tegrating PD-1&amp;CD-28 chimeric antigen complexes. While CAR-T therapy excels against hematological malignancies, challenges remain, such as immune checkpoint upregulation and potential toxicity. The research aims to optimize CAR-T therapys efficacy through innovative modifications. Alternative strategies like multi-targeted CARs and combina-tions with immune checkpoint inhibitors are explored. Overall, this study advances can-cer therapy by addressing CAR-T therapys limitations and proposing complementary strategies for improved personalized treatments.

Clinical outcomes after idecabtagene vicleucel in older patients with multiple myeloma: a multicenter real-world experience

AbstractThe safety and efficacy of chimeric antigen receptor T-cell therapy is not well described in older patients, a population that has higher frailty and comorbidities. In this multicenter retrospective study, we evaluated clinical outcomes along with frailty and geriatric characteristics such as comorbidities, polypharmacy, falls, neuropathy, organ dysfunction, and performance status in younger (aged <65 years) vs older (aged ≥65 years) patients who received commercial idecabtagene vicleucel (ide-cel). A total of 156 patients (n = 75, aged ≥65 years) were infused with ide-cel by data cutoff. In older patients (median age: 69 years; range, 65-83; 66.7% frail; 77.3% did not meet KarMMa eligibility criteria), with a median follow-up duration of 14.2 months, best overall response rate (ORR) was 86.7%, which was comparable with pivotal KarMMa study results (ORR: 73%). Median progression-free survival and overall survival in older patients were 9.1 months and 26.5 months, respectively. Grade ≥3 cytokine-release syndrome and immune effector cell–associated neurotoxicity syndrome were observed in 1% and 4% of older patients, respectively. Compared with younger patients, the older patients had significantly higher prevalence of frailty, geriatric characteristics such as polypharmacy (≥5 drugs; 97%), ≥4 comorbidities (69%), and organ dysfunction (35%; P < .05). The safety and efficacy of ide-cel therapy were similar in younger and older patients. Frailty and geriatric characteristics such as polypharmacy, comorbidities, and organ dysfunction in older patients did not confer an inferior overall outcome.