Shift from widespread to tailored antifungal prophylaxis in lymphoma patients treated with CD19 CAR T cell therapy: Results from a large retrospective cohort Journal Article
| Authors: | Melica, G.; Luna de Abia, A.; Shah, G. L.; Devlin, S.; Corona, M.; Fein, J.; Dahi, P. B.; Giralt, S. A.; Lin, R. J.; Palomba, M. L.; Parascondola, A.; Park, J.; Salles, G.; Saldia, A.; Scordo, M.; Shouval, R.; Perales, M. A.; Seo, S. K. |
| Article Title: | Shift from widespread to tailored antifungal prophylaxis in lymphoma patients treated with CD19 CAR T cell therapy: Results from a large retrospective cohort |
| Abstract: | Patients undergoing CD19 chimeric antigen receptor (CAR)–T cell therapy exhibit multiple immune deficits that may increase their susceptibility to infections. Invasive fungal infections (IFIs) are life-threatening events in the setting of hematologic diseases. However, there is ongoing debate regarding the optimal role and duration of antifungal prophylaxis in this specific patient population. The objective of this study was to provide a comprehensive overview of the evolution of IFI prophylactic strategies over time and to assess IFI incidence rates in a cohort of patients with relapsed or refractory (R/R) lymphoma treated with CAR-T cell therapy. A single-center retrospective study was conducted on a cohort of patients with R/R B cell lymphoma treated with CD19 CAR-T cell therapy between April 2016 and March 2023. Group A (April 2016–August 2020) consisted of patients primarily treated with fluconazole, irrespective of their individual IFI risk profile. In Group B (September 2020–March 2023) antifungal prophylaxis was recommended only for high-risk patients. Overall, 330 patients were included. Antifungal prophylaxis was prescribed to 119/142 (84%) patients in Group A and 58/188 (31%) in Group B (P < .001). Anti-mold azoles were prescribed to 8 (5.6%) patients in Group A and 21 (11.2%) patients in Group B. In Group A, 42 (29%) patients were switched to another antifungal, 9 (21%) because of toxicity, with 6 cases of transaminitis and 3 cases of prolonged QTc. In Group B, 21 (11.2%) patients were switched to the antifungal drug, mainly from fluconazole or micafungin to a mold-active agent following revised guidelines. No difference was found in liver toxicity between the two groups at infusion, day 10, and day 30. No significant differences were observed between the groups. IFIs following CAR-T cell therapy were rare, with 1 case of cryptococcal meningoencephalitis in group A (.7%) and 1 case of invasive aspergillosis in Group B (.5%), both occurring in patients on micafungin prophylaxis. In this large single-center cohort of patients with R/R lymphoma treated with CAR-T cells, we show that individualized prophylaxis, alongside careful management of CAR-T cell–related toxicities such as CRS, was associated with a very low IFI rate, avoiding the risk of unnecessary toxicities, drug–drug interactions, and high costs. © 2024 The American Society for Transplantation and Cellular Therapy |
| Keywords: | adult; aged; middle aged; retrospective studies; major clinical study; prednisone; neutropenia; cancer recurrence; drug withdrawal; treatment duration; follow up; cancer grading; c reactive protein; incidence; qt prolongation; cohort analysis; antifungal agent; retrospective study; high risk patient; alanine aminotransferase; alkaline phosphatase; aspartate aminotransferase; bilirubin; b cell lymphoma; immunology; prophylaxis; lymphoma; risk stratification; drug therapy; drug substitution; cotrimoxazole; adverse drug reaction; fluconazole; therapy; posaconazole; voriconazole; antifungal agents; adoptive immunotherapy; immunotherapy, adoptive; lung aspergillosis; cd19 antigen; antigens, cd19; autologous hematopoietic stem cell transplantation; micafungin; fibrinogen; prevention and control; pyrrole derivative; antifungal activity; adverse event; complication; hypertransaminasemia; demographics; systemic mycosis; diffuse large b cell lymphoma; pneumocystosis; antifungal prophylaxis; tocilizumab; Common Terminology Criteria for Adverse Events; ibrutinib; humans; human; male; female; article; absolute neutrophil count; tisagenlecleucel t; chimeric antigen receptor t-cell immunotherapy; invasive fungal infections; axicabtagene ciloleucel; lisocabtagene maraleucel; isavuconazole; brexucabtagene autoleucel; treatment switching; bridging therapy; car-t cell toxicity; r/r b cell lymphoma; cryptococcal meningoencephalitis |
| Journal Title: | Transplantation and Cellular Therapy |
| Volume: | 31 |
| Issue: | 1 |
| ISSN: | 2666-6375 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2025-01-01 |
| Start Page: | 36 |
| End Page: | 44 |
| Language: | English |
| DOI: | 10.1016/j.jtct.2024.10.010 |
| PUBMED: | 39448032 |
| PROVIDER: | scopus |
| PMCID: | PMC11780678 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PubMed record and PDF. Corresponding MSK author is Susan Seo -- Source: Scopus |
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