Toxicities following CAR-T therapy for hematological malignancies

Hernani, Rafael; Benzaquén, Ana; Solano, Carlos

doi:10.1016/j.ctrv.2022.102479

Cited by 26 publications

(15 citation statements)

References 158 publications

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“…Neurotoxicity in the form of Immune effector cell-associated neurotoxicity syndrome (ICANS) may be seen alone or in addition to CRS [37,40]. These reactions are currently managed with the Il-6 inhibitor tocilizumab for low grade reactions, with the addition of corticosteroids for refractory cases or concomitant ICANS [37,39]. In oncology, higher tumor burden leads to higher in vivo CAR-T expansion which is associated with increased rates of higher grade CRS [41].…”

Section: Introductionmentioning

confidence: 99%

Chimeric antigen receptors: “CARs” in the fast lane for rheumatology

Johnson,

Koumpouras

2024

Current Opinion in Rheumatology

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Purpose of review Recent advances in hematology-oncology have pioneered cell-mediated elimination of pathologic B-cell populations employing chimeric antigen receptor (CAR) T cells. In this review, we discuss recent adoption of CAR-T treatment for severe refractory autoimmune disease. We highlight unique aspects of the autoimmune model and review current clinical data regarding treatment of rheumatologic disease. Recent findings To date, several CAR-Ts are FDA approved for Multiple Myeloma and B-cell malignancies and have demonstrated extraordinary clinical responses in refractory disease. Realizing the central role of B-cells in certain autoimmune diseases, CAR-T is now being explored for achieving drug-free remission induction, and potentially cure, of several rheumatologic diseases. The largest experience to date in the field of autoimmunity, building off the University Hospital Erlangen groups’ earlier success treating a single patient with CD19-CAR in severe refractory SLE, Mackensen et al. enrolled five patients in a compassionate use program. Following autologous CD19-CAR T infusion, they demonstrated drug-free clinical and laboratory remission for at least 12 months in all five patients, with reconstitution of B cells expressing a naïve phenotype. Summary CAR-T treatment has shown striking drug-free responses in severe lupus and other autoimmune diseases, creating a need for further exploration and development.

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Section: Introductionmentioning

confidence: 99%

Chimeric antigen receptors: “CARs” in the fast lane for rheumatology

Johnson,

Koumpouras

2024

Current Opinion in Rheumatology

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“…Inflammatory markers, such as ferritin, c-reactive protein (CRP) and interleukin-6 (IL-6) have been widely proved to be related with cytokine release syndrome (CRS) during CAR-T cell therapy (12)(13)(14)(15). The occurrence of severe CRS is associated with high early mortality (16), and the CRS-related complications such as delayed hematopoietic recovery, coagulopathy and cardiac disorders will also dispose patients to poor outcomes (17)(18)(19). To date, there are limited data regarding the correlation of circulating inflammatory markers and the prognosis of CAR-T therapy in the setting of MM.…”

Section: Introductionmentioning

confidence: 99%

A combination of pre-infusion serum ferritin, CRP and IL-6 predicts outcome in relapsed/refractory multiple myeloma patients treated with CAR-T cells

Liu

Jie

et al. 2023

Front. Immunol.

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BackgroundChimeric antigen receptor - T (CAR-T) cell therapy has shown remarkable efficacy in patients with relapsed/refractory multiple myeloma (R/R MM). However, a subset of patients still experienced progression or relapse, and the predictors of prognosis are little known. We analyzed the inflammatory markers before CAR-T cell infusion, to clarify their correlation with survival and toxicity.MethodsThis study involved 109 R/R MM patients who received CAR-T therapy between June 2017 and July 2021. Inflammatory markers, including ferritin, c-reactive protein (CRP), and interleukin-6 (IL-6) before CAR-T cell infusion were detected and then categorized by quartiles. Adverse events and clinical outcomes were compared between patients with upper quartile of inflammatory markers and patients with lower three quartiles of inflammatory markers. An inflammatory prognostic index (InPI) based on these three inflammatory markers was developed in this study. Patients were divided into 3 groups according to the InPI score, progression-free survival (PFS) and overall survival (OS) were compared among the groups. In addition, we explored the correlation between cytokine release syndrome (CRS) and pre-infusion inflammatory markers.ResultsWe found that the pre-infusion high ferritin (hazard ratio [HR], 3.382; 95% confidence interval [CI], 1.667 to 6.863; P = .0007), high CRP (HR, 2.043; 95% CI, 1.019 to 4.097; P = .044), and high IL-6 (HR, 3.298; 95% CI, 1.598 to 6.808; P = .0013) were significantly associated with inferior OS. The formula of the InPI score was based on the HR value of these 3 variables. Three risk groups were formed: (good, 0 to 0.5 point; intermediate, 1 to 1.5 points; poor, 2 to 2.5 points). Median OS for patients with good, intermediate, and poor InPI was not reached, 24 months, and 4 months, respectively, and median PFS was 19.1 months, 12.3 months, and 2.9 months, respectively. In the cox proportional hazards model, poor InPI remained an independent prognostic factor for PFS and OS. Pre-infusion ferritin was negatively associated with CAR T-cell expansion normalized to baseline tumor burden. Spearman correlation analysis showed that pre-infusion ferritin and IL-6 levels positively correlated with the grade of CRS (P = .0369 and P = .0117, respectively). The incidence of severe CRS was higher in patients with high IL-6 compared with patients with low IL-6 (26% vs. 9%, P = .0405). Pre-infusion ferritin, CRP and IL-6 were positively correlated with each peak values within the first month after infusion.ConclusionsOur results suggest that patients with elevated inflammation markers before CAR-T cell infusion are more likely to have poor prognosis.

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“…The major impediments to effective CAR‐T therapy involve life‐threatening toxicities following CAR‐T infusion. Furthermore, poor persistence, antigen escape, immune rejection of therapeutics, and technological obstacles connected with the intricate manufacturing processes warrant consideration 10 . While there are many challenges, CAR‐T cell immunotherapy remains a significant novel concept.…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, poor persistence, antigen escape, immune rejection of therapeutics, and technological obstacles connected with the intricate manufacturing processes warrant consideration. 10 While there are many challenges, CAR-T cell immunotherapy remains a significant novel concept. More trials have been registered to assess its applications in treating hematological cancers.…”

Section: Introductionmentioning

confidence: 99%

CAR‐T cell therapy in hematological malignancies: Where are we now and where are we heading for?

Khan,

Asija,

Pendhari

et al. 2023

European J of Haematology

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Chimeric antigen receptor T (CAR‐T) therapy has emerged as a revolutionary new pillar in cancer care, particularly in relapsed/refractory (r/r) B‐cell malignancies. Following impressive clinical outcomes in hematological malignancies, the FDA‐approved six CAR‐T cell products for indications such as lymphoma, leukemia, and myeloma. Despite the numerous advantages of CAR‐T cell treatment, several challenges exist that interfere with its therapeutic efficacy. Serious adverse effects connected with the treatment continue to be a major concern. In addition, poor persistence of therapeutics and antigen escape frequently result in tumor relapse. Exorbitant treatment cost further remains a significant barrier to its effective implementation, limiting its accessibility. This review presents progress of CAR‐T research, the key obstacles that hamper promising outcomes for patients with hematological malignancies, and a few strategies to overcome them.

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Toxicities following CAR-T therapy for hematological malignancies

Cited by 26 publications

References 158 publications

Chimeric antigen receptors: “CARs” in the fast lane for rheumatology

Chimeric antigen receptors: “CARs” in the fast lane for rheumatology

A combination of pre-infusion serum ferritin, CRP and IL-6 predicts outcome in relapsed/refractory multiple myeloma patients treated with CAR-T cells

CAR‐T cell therapy in hematological malignancies: Where are we now and where are we heading for?

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