Nadarevic, Ella

Abstract Background Chimeric antigen receptor T-cell therapy (CAR-T) has transformed care for relapsed or refractory B-cell malignancies. Cytokine-release syndrome (CRS) complicates most infusions, yet the ensuing infection risk is ill-defined.Table 1Profile of 230 patients undergoing with CRS following CAR-T therapyTable 2Cytokine Release Syndrome Severity, Management, and Early Outcomes by 90-Day Infection Status Methods CAR-T recipients who developed CRS at our institution from 1 Jan 2018 to 3 June 2024 were retrospectively reviewed. Variables were abstracted into REDCap. CRS was graded with American Society for Transplantation and Cellular Therapy (ASTCT) criteria. All infections occuring after CRS onset to day 90 were adjudicated. Continuous data are reported as medians with interquartile ranges (IQR); categorical data as counts and percentages. Table 2 comparisons used Mann-Whitney U for continuous and χ² or Fisher exact tests for categorical variables (two sided, P < 0.05). Multivariable logistic regression was used to identify independent predictors of infection.Table 3Infectious Syndromes, Pathogens, and Timing of First Infection Following CRS Onset Results Among 230 CRS cases, median age was 64 yr (IQR 57–70) and 59% were male. Non-Hodgkin lymphoma accounted for 62% and multiple myeloma for 38%. Median prior therapy lines were 3. CRS was grade 1–2 in 97%. CAR-HEMATOTOX was low in 156 (68%) (Table 1). Within 90 days, 51 patients (22%) developed infection; median onset was 15 days (IQR 5–26). Infected patients more often received anakinra (22% vs 8%, p = 0.02) and required ICU care (18% vs 7%, p = 0.05); grade ≥3 CRS trended higher (10% vs 3%, p = 0.06). In multivariable analysis adjusting for age, CAR-HEMATOTOX, ICU admission, and anakinra, both ICU admission (aOR 2.06; 95% CI 0.70–5.81; p = 0.18) and anakinra use (aOR 2.18; 95% CI 0.83–5.53; p = 0.10) were associated with higher infection odds, though not statistically significant. 90-day survival was 88% with infection versus 96% without (p = 0.09) (Table 2). 51 infectious episodes were documented: bacteremia 22; gastrointestinal 9; central line–associated bloodstream infection 7; other sites 22. Bacteria caused 59%, viruses 37% (15 CMV, 4 SARS-CoV-2), and fungi 4%. No infection-related deaths occurred (Table 3). Conclusion Infection was common after CRS, but did not alter early survival. Anakinra exposure and ICU admission were associated with a higher likelihood of infection, though not statistically significant. Targeted surveillance should focus on patients requiring intensified CRS management. Disclosures Yi Lin, M.D., BMS: Board Member|Caribou: Advisor/Consultant|Genentech: Board Member|Jassen: Board Member|Jassen: Steering Committee|Kite/Gilead: Steering Committee|Legend: Board Member|NexImmune: Advisor/Consultant|NexT Therapeutics: Board Member|Pfizer: Board Member|Regeneron: Board Member|Sanofi: Board Member|Tessera: Board Member Paschalis Vergidis, MD, MSc, Current Fungal Infection Reports: Honoraria|F2G: Grant/Research Support|Merck Manuals: Honoraria|Mundipharma: Grant/Research Support|Scynexis: Advisor/Consultant|Scynexis: Grant/Research Support

We report a case of a triazole and echinocandin-resistant C. glabrata right shoulder prosthetic joint infection in a 60-year-old woman. The patient underwent surgery and received the novel triterpenoid antifungal agent ibrexafungerp. She initially improved, but relapsed four months post-treatment. This case highlights the potential role of ibrexafungerp in multidrug-resistant Candida infections.

Abstract Background Invasive mold infections (IMI) lead to significant morbidity and mortality in patients with hematologic malignancies. We provide patients deemed at higher risk mold active prophylaxis but still observe breakthrough IMIs. The purpose of this study was to evaluate risk factors associated with these breakthrough infections. Methods We conducted a retrospective cohort study of adult hematologic patients at 3 tertiary care medical centers from November 19, 2011 - August 6, 2021. Only IMI cases defined as proven or probable per EORTC/MSG criteria were included. Patients with IMIs who received a minimum of 7 days of mold active prophylaxis were classified as breakthrough infection. We performed logistical regression analysis to identify risk factors associated with breakthrough IMI. Results Majority of cases were probable IMIs, with 16 (28.6%) and 25 (15.7%) proven cases amongst breakthrough and non-breakthrough IMIs, respectively. Many variables indicative of weakened host immune system, including neutropenia and hypogammaglobulinemia, were associated with breakthrough IMIs, albeit not statistically significant (Table 1). Multivariate analysis revealed history of AML (OR 4.20, 95% CI 2.03-8.88; p < 0.001) and receipt of HCT (OR 3.37, 95% CI 1.46-8.11; p = 0.003) to be independent host risk factors for breakthrough IMI. Of all the pathogens, Fusarium (OR 4.38, 95% CI 1.56-12.56; p = 0.005) and Mucorales (OR 5.59, 95% CI 2.11-15.61; p < 0.001) were significantly likely to lead to breakthrough IMIs. 26 (47.3%) of the breakthrough IMIs were on appropriately dosed prophylaxis at the time of infection, with only 9 (16.4%) found to be subtherapeutic (Table 2). Overall, mortality was slightly higher amongst the breakthrough IMIs (51.8% vs 45.9%) but not significantly different (Figure 1). Conclusion In our cohort of probable/proven IMIs, we did not observe any significant difference in mortality between patients with breakthrough IMIs and those not on mold active prophylaxis. Even with appropriate prophylactic dosing, breakthrough infections occurred, irrespective of agent. Our study demonstrates that host risk factors and the causative pathogen are clinically more pertinent than the prophylaxis regimen in breakthrough IMIs. Disclosures Paschalis Vergidis, MD, MSc, AbbVie: Advisor/Consultant|Ansun Biopharma: Grant/Research Support|Cidara Therapeutics: Grant/Research Support|F2G: Grant/Research Support|Scynexis: Advisor/Consultant|Scynexis: Grant/Research Support