Chen, S

Objective We aim to identify risk factors to enable stratification of patients' susceptibility to inflammatory arthritis immune‐related adverse events (IA‐irAEs). This retrospective study mainly examines whether preexisting osteoarthritis (OA) increases the likelihood of de novo IA‐irAEs. Methods The prevalence of OA among immune checkpoint inhibitor (ICI)–treated patients who developed IA‐irAE, those who developed other types of irAEs but not IA (non‐IA irAEs), and those who did not develop any irAEs (non‐irAEs) were compared. Electronic medical records were reviewed to extract demographic, clinical, and laboratory data. Group comparisons and logistic regression analyses were performed. Results A total of 181 de novo IA‐irAE patients, 140 non‐IA irAE patients, and 170 non‐irAE patients were included. The prevalence of OA was significantly higher in the IA‐irAE group (69%) than in the non‐IA irAE group (48%) and the non‐irAE group (48%) (both P < 0.001). The IA‐irAE group demonstrated a higher frequency of multisite OA, with more predominant hand involvement (62%) than the non‐IA irAE with OA group (13%) and the non‐irAE with OA group (13%) (both P < 0.001). A family history of autoimmune disease (AID) (odds ratio [OR] 2.03, 95% confidence interval [CI] 1.02–4.05), preexisting OA (OR 2.88, 95% CI 1.85–4.52), and melanoma (OR 2.63, 95% CI 1.56–4.47) were identified as risk factors for the development of IA‐irAE. Conclusion OA was more prevalent among ICI‐treated patients developing IA‐irAE than those who were not. Hand OA was the most common OA pattern in IA‐irAE patients. Preexisting OA, melanoma, and a family history of AID were associated with IA‐irAE.

Abstract Background Chimeric antigen receptor (CAR) T-cell therapy has been revolutionary in the treatment of blood cancers, but has been associated with arrhythmias such as atrial fibrillation (AF). The treatment course and cardiovascular outcomes of patients who develop new or recurrent AF after CAR-T has yet to be explored. Methods We extracted a cohort of patients who underwent CAR T-cell therapy between 2016 and 2022. The endpoint of interest was defined as the first episode of new or recurrent AF during or after CAR-T infusion. Patients with persistent or permanent AF were not counted as events. Tocilizumab use was not counted for patients who had an AF event more than 30 days after CAR-T infusion. Chart review was used to delineate patient treatments and outcomes. Survival analyses techniques were used to define risk of new or recurrent AF. Results There were 328 patients who underwent CAR T-cell therapy between 2016 and 2022, of which 41 had prior history of AF. Overall, there were 10 new and 9 recurrent AF events after CAR T-cell infusion, with a composite cumulative incidence risk of 5.8%. The majority of these events occurred within 30 days of receiving CAR-T (N=14, 73.7%). All events that occurred after 30 days were associated with significant hospitalizations unrelated to CAR-T. Rate control was the preferred method of treatment, with beta blockers being the preferred first-line therapy for both patients on and not on baseline beta blockers (Table). 2 patients were given amiodarone prophylactically prior to CAR-T infusion. Only 1 patient received cardioversion, 15 days after the AF event, but had recurrence shortly thereafter. Only 2 patients were on chronic anticoagulation, and both had history of AF prior to CAR-T. Tocilizumab was given to 9 patients (47.4%) before the onset of AF and not significantly associated to decreased risk of developing new or recurrent AF (HR 1.16, CI 0.47-2.83, P=0.75). Tocilizumab was more likely given to patients with higher cytokine release syndrome and neurotoxicity grading (Figure). There were no myocardial infarctions or strokes. Conclusion Atrial fibrillation is a rare complication of CAR T-cell therapy. Rate-control strategies remain the preferred method of treatment. Very few patients were given anticoagulation, but the incidence of subsequent stroke was negligible. More investigation will need to be undertaken to determine methods of preventing AF in the setting of CAR-T therapy.CAR-T AF Patient Case Series

Abstract Background Chimeric antigen receptor (CAR) T-cell therapy has been revolutionary in the treatment of blood cancers, but has been associated with arrhythmias such as atrial fibrillation (AF). Whether the incidence of AF has changed over time and if contributing risk factors are present remains to be defined. Methods Leveraging the Mayo Electronic Medical Record, we extracted a cohort of patients who underwent CAR T-cell therapy between 2016 and 2022. From this cohort, we identified those who had a diagnosis of AF at any point. We then defined the endpoint of interest as the first episode of new or recurrent AF during or after CAR T-cell infusion. Fine and Gray subdistribution hazard modeling was used to calculate the association of patient characteristics to the endpoint of interest. Variables with P&lt;0.20 in univariate modeling were chosen for the multivariate model. Significance was defined as P&lt;0.05. Results There were 328 patients who underwent CAR T-cell therapy between 2016 and 2022. Of this cohort, 27 (8.2%) patients had a pre-existing diagnosis of AF, of which 6 had recurrence of AF after CAR T (22.2%), while 21 (77.8%) did not. Of the 301 patients without a prior history of AF, 8 (2.7%) patients developed new-onset AF after CAR T. The majority of the 14 new or recurrent AF events (4.3% overall incidence) occurred within 30 days of receiving CAR T (N=10, 71.4%), the remainder after 180 days (Figure 1). No trend in declining incidence over time was noted. Prior AF, neurotoxicity, and inflammation (cytokine release syndrome and macrophage activating syndrome-like (MAS-L)) were strongly associated with the risk of developing new or recurrent AF (Table 1). Only presence of MAS-L remained an independent predictor in the multivariate model (HR 15.4, 95% CI 3.9-61.2, P&lt;0.001). Conclusion AF is mainly seen early following CAR T-cell therapy, and mainly in association with severe inflammatory responses. Early and aggressive treatment of CRS and MAS-L may be recommendable for patients undergoing CAR-T therapy, especially for those with a prior history of AF.