Background aimsB-cell maturation antigen (BCMA)-targeted chimeric antigen receptor-T cell (CAR-T) therapy is used for refractory or relapsed multiple myeloma (r/r MM). However, CAR-T-related tumor lysis syndrome (TLS) has been observed. We aimed to elucidate the incidence, clinical and laboratory characteristics, and prognosis of CAR-T cell-related TLS.MethodsPatients (n=105) with r/r MM treated with BCMA-targeted CAR-T cell therapy were included. Patient characteristics, laboratory parameters, and clinical outcomes were assessed.ResultsEighteen (17.1%) patients developed TLS after BCMA-targeted CAR-T cell therapy. The median time till TLS onset was 8 days. Patients with TLS had steep rise in uric acid (UA), creatinine, and lactate dehydrogenase (LDH) within 6 days following CAR-T cell infusion and presented earlier and persistent escalation of cytokines (C-reactive protein [CRP], interleukin-6 [IL-6], interferon-γ [IFN-γ], and ferritin levels). All 18 patients had cytokine release syndrome (CRS), of which 13 (72.2%) developed grade 3–4 CRS. Three of 18 patients (16.7%) developed immune effector cell-associated neurotoxicity syndrome (ICANS): two patients with grade 1 ICANS and one with grade 2 ICANS. TLS development had a negative effect on the objective response rate (77.8% in the TLS group vs. 95.4% in the non-TLS group, p<0.01). During the median follow-up of 15.1 months, the median PFS was poorer of patients with TLS (median: 3.4 months in the TLS group vs. 14.7 months in the non-TLS group, p<0.001, hazard ratio [HR]=3.5 [95% confidence interval [CI] 1.5–8.5]). Also, TLS development exhibited significant effects on OS (median: 5.0 months in the TLS group vs. 39.8 months in the non-TLS group, p<0.001, hazard ratio [HR]=3.7 [95% CI 1.3–10.3]). TLS was associated with a higher tumor burden, elevated baseline creatinine and UA levels, severe CRS, pronounced CAR-T cell expansion, and corticosteroid use.ConclusionTLS is a frequently observed CAR-T therapy complication and negatively influences clinical response and prognosis. Close monitoring for TLS should be implemented during CAR-T cell therapy, especially for those at high TLS risk.
Background: The NCCN clinical guidelines recommended core needle biopsy for breast lesions classified as Breast Imaging Reporting and Data System (BI-RADS) 4, while category 4A lesions are only 2-10% likely to be malignant. Thus, a large number of biopsies of BI-RADS 4A lesions were ultimately determined to be benign, and those unnecessary biopsies may incur additional costs and pains. However, it is important to emphasize that the current risk prediction model focuses primarily on the details and complex risk features of US or MG findings, which may be difficult to apply in order to benefit from the model. To stratify and manage BI-RADS 4A lesions effectively and efficiently, a more effective and practical predictive model must be developed. Methods: We retrospectively analyzed 465 patients with BI-RADS ultrasonography (US) category 4A lesions, diagnosed between January 2019 and July 2019 in Tianjin Medical University Cancer Institute and Hospital and National Clinical Research Center for Cancer. Univariate and multivariate logistic regression analyses were conducted to identify risk factors. To stratify and predict the malignancy of BI-RADS 4A lesions, a nomogram combining the risk factors was constructed based on the multivariate logistic regression results. In order to determine the predictive performance of our predictive model, we used the concordance index (C-index), calibration curve, and receiver operating characteristic (ROC), and the decision curve analysis (DCA) to assess the clinical benefits. Results: Based on our analysis, 16.3% (76 out of 465) of patients were pathologically diagnosed with malignant lesions, while 83.6% (389 out of 465) were diagnosed with benign lesions. According to univariate and multivariate logistic regression analysis, age (OR = 3.414, 95%CI:1.849-6.303), nipple discharge (OR = .326, 95%CI:0.157-.835), palpable lesions (OR = 1.907, 95%CI:1.004-3.621), uncircumscribed margin (US) (OR = 1.732, 95%CI:1.033-2.905), calcification (mammography, MG) (OR = 2.384, 95%CI:1.366-4.161), BI-RADS(MG) (OR = 5.345, 95%CI:2.934-9.736) were incorporated into the predictive nomogram (C-index = .773). There was good agreement between the predicted risk and the observed probability of recurrence. Furthermore, we determined that 153 was the best cutoff score for distinguishing between patients in the low- and high-risk groups. Malignant lesions were significantly more prevalent in high-risk patients than in low-risk patients. Conclusion: Based on clinical, US, and MG features, we present a predictive nomogram to reliably predict the malignancy risk of BI-RADS(US) 4A lesions, which may assist clinicians in the selection of patients at low risk of malignancy and reduce the number of false-positive biopsies.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.