Characterizing the Real-World Risks of Kidney Injuries Associated with Chimeric Antigen Receptor T Cell Therapies—Evidence and Safety

Acute Kidney Injury After the CAR-T Therapy Tisagenlecleucel

Cellular Dynamics Following CAR T Cell Therapy Are Associated with Response, Resistance and Cytokine Release Syndrome in Relapsed/Refractory Multiple Myeloma

Multimodality Prevention of Contrast-Induced Acute Kidney Injury

Nephrotoxicity of Antimicrobials and Antibiotics.

Shortening the ex vivo culture of CD19-specific CAR T-cells retains potent efficacy against acute lymphoblastic leukemia without CAR T-cell-related encephalopathy syndrome or severe cytokine release syndrome.

Case Scenario: Hemodynamic Management of Postoperative Acute Kidney Injury

Perioperative Acute Kidney Injury

A Systematic Meta-Analysis of Cytokine Release Syndrome Incidence in B-Cell Maturation Antigen-Targeting Chimeric Antigen Receptor T-Cell Therapy and Bispecific Antibodies for Patients with Relapsed and/or Refractory Multiple Myeloma

Managing CAR T-Cell Toxicity: Impact of Steroid Prophylaxis on Toxicity and Outcomes

Comparative Analysis of Mortality from Serious Adverse Events Associated with CAR-T Therapies

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

Promoter usage regulating the surface density of CAR molecules may modulate the kinetics of CAR-T cells in vivo

Acute kidney injury (AKI) occurs in 30% of patients infused with chimeric antigen receptor (CAR) T-cells. The purpose of this study was to identify risk factors and long-term outcomes after AKI in patients who received CAR T-cell therapy. Medical records of 115 adult patients with R/R hematological malignancies treated with CD19-targeted CAR T-cells at Vall d'Hebron University Hospital between July 2018 and May 2021. Baseline demographic data including age, gender, ethnicity, body mass index (BMI), and co-morbidities, as well as the type of hematological neoplasia and prior lines of therapy were collected. Laboratory parameters including serum creatinine and whole blood hemoglobin were retrospectively reviewed and values were gathered for days +1, +7, +14, +21, and +28 post-infusion. A total of 24/115 (21%) patients developed AKI related to CAR T-cell therapy; 6/24 with AKI over chronic kidney disease (CKD). Two patients had AKI in the context of lymphodepleting (LD) chemotherapy and the other 22 after CAR T-cell infusion, starting at day+1 in 3 patients, day+7 in 13 patients, day +14 in 1 patient, day+21 in 2 patients, and day+28 in 3 patients. Renal function was recovered in 19/24 (79%) patients within the first month after infusion. Male gender, CKD, cytokine release syndrome (CRS), and immune effector cell-associated neurotoxicity syndrome (ICANS) were associated with AKI. Male gender, CKD, ICANS grade ≥3 and CRS grade ≥2 were identified as independent risk factors for AKI on multivariable analysis. In terms of the most frequent CAR T-cell related complications, CRS was observed in 95 (82%) patients and ICANS in 33 (29%) patients. Steroids were required in 34 (30%) patients and tocilizumab in 37 (32%) patients. Six (5%) patients were admitted to the intensive care unit (1 for septic shock, 4 for CRS grade ≥2 associated to ICANS grade ≥2, and 1 for CRS grade ≥3). A total of 5 (4.4%) patients died in the first 30 days after CAR T-cell infusion for reasons other than disease progression, including 4 cases of infectious complications and 1 of heart failure. Our results suggest that AKI is a frequent but mild adverse event, with fast recovery in most patients.

Chimeric antigen receptor T (CAR-T) cell therapy has revolutionized the treatment of relapsed/refractory (R/R) B-cell derived hematological malignancies, including acute lymphoblastic leukemia (ALL), B-cell non-Hodgkin lymphoma (B-NHL), and multiple myeloma (MM). CD19-targeted CAR-T cells yield complete remission (CR) rates of about 90% in R/R ALL and about 50% in R/R NHL, respectively, while BCMA-targeted CAR-T cells yield CR rate of about 50%−80% in R/R MM. Notably, the US Food and Drug Administration have approved six CAR-T cell products (tisagenlecleucel, axicabtagene ciloleucel, brexucabtagene autoleucel, lisocabtagene maraleucel, idecabtagene vicleucel, and ciltacabtagene autoleucel) for the treatment of R/R B-NHL, R/R ALL, and R/R MM. However, some patients might not respond to such therapy or quickly relapse after CAR-T cell infusion, which is likely due to the dysfunction and poor persistence of CAR-T cells or the modulation of specific antigen. Thus, alternative treatment strategies must be investigated. In addition, accumulating research have been conducted to discover novel target of antigens with therapeutic efficacy and utility for generating CAR-T cells against acute myeloid leukemia (AML). Safety during CAR-T cell treatment is another important issue, concerning complications such as cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome (ICANS), pancytopenia, and infection. Despite the fact that the majority of those adverse effects are minimal, the risk of a life-threatening situation still exists. Cautious treatment for severe adverse events requires a multidisciplinary approach with involvement of not only oncologists but also other internal medicine doctors to guarantee diagnosis and treatment in time. Therefore, it is of vital importance to understand the novel advances of CAR-T cell therapy. This special issue of ImmunoMedicine focuses on novel developments of CAR-T cell therapy for hematological malignancies. The review from Xiangmin Wang (https://doi.org/10.1002/imed.1030) summarized the non-BCMA targeted CAR-T cell therapies for MM. Novel targets including CS1, CD38, CD138, NKG2D, CD70, TACI, and etc. might have the potential to prevent the recurrence and enhance treatment efficiency. The review from Elaine Tan Su Yin (https://doi.org/10.1002/imed.1039) summarized the current breakthrough and future perspectives of CD20-targeted CAR-T cell therapy for hematologic malignancies, especially for R/R B-NHL. The review from Yue Huang (https://doi.org/10.1002/imed.1031) summarized the current achievement and potential AML-associated cell markers of CAR-T cell therapy in AML preclinical studies and clinical trials, and discusses the future directions of CAR-T cell therapy in patients with AML. The review from Yuanyuan Hao (https://doi.org/10.1002/imed.1029) summarized the effects of tumor-derived exosomes (TEXs) on the survival and functions of T cell subsets, as well as their clinical applications. This special issue also contains three original research articles reporting clinical trials of CAR-T cell therapy. Linghui Zhou et al. (https://doi.org/10.1002/imed.1036) reported the data of infections post CAR-T cell therapy, and found that it was a common complication in patients with hematological malignancies treated by CD19 CAR-T cells, which means clinicians should pay more attention to such situations. Kaiting Tang et al. (https://doi.org/10.1002/imed.1037) presented three cases of compassionate CAR-T cell therapy in advanced B-ALL, and shared their experiences on treating patients with high disease burden. Yue Huang et al. (https://doi.org/10.1002/imed.1032) reported an R/R ALL patient with high leukemia burden and central nervous system involvement, who responded to donor-derived HLA-matched allogeneic CAR-T treatment and achieved quick CR. We thank all the authors for their insightful contributions. This special issue provides an overview of the current knowledge regarding the most recent advances of CAR-T cell therapy, including CAR-T cell function, diverse applications, and complications with coping strategies. We hope that this issue will appeal to researchers as they explore fundamental and clinical aspects of CAR-T cell therapy.

Early Cytopenias and Infections Following Chimeric Antigen Receptor T-Cell Therapy: A Single Center Experience