$Tisagenlecleucel infusion in patients with relapsed/refractory ALL and concurrent serious infection$
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Tisagenlecleucel infusion in patients with relapsed/refractory ALL and concurrent serious infection

Background Tisagenlecleucel, an anti-CD19 chimeric antigen receptor T (CAR-T) cell therapy, has demonstrated durable efficacy and a manageable safety profile in pediatric and young adult patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) in the ELIANA pivotal trial and rea...

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Autores principales:	Weijie Li, Keith J August, Erin M Hall, Dwight E Yin, Rakesh K Goyal, Atif A Ahmed, Grace S Mitchell, Shawn D St. Peter, Terrie G Flatt, Ibrahim A Ahmed, Richard J Hendrickson, G Doug Myers
Formato:	article
Lenguaje:	EN
Publicado:	BMJ Publishing Group 2021
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/ebd8b85ed1f64889854a9550a505497f
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spelling	oai:doaj.org-article:ebd8b85ed1f64889854a9550a505497f2021-11-15T22:00:04ZTisagenlecleucel infusion in patients with relapsed/refractory ALL and concurrent serious infection10.1136/jitc-2020-0012252051-1426https://doaj.org/article/ebd8b85ed1f64889854a9550a505497f2021-01-01T00:00:00Zhttps://jitc.bmj.com/content/9/1/e001225.fullhttps://doaj.org/toc/2051-1426Background Tisagenlecleucel, an anti-CD19 chimeric antigen receptor T (CAR-T) cell therapy, has demonstrated durable efficacy and a manageable safety profile in pediatric and young adult patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) in the ELIANA pivotal trial and real-world experience. Experience from investigator-led studies prior to ELIANA suggests that infections and inflammatory conditions may exacerbate the severity of cytokine release syndrome (CRS) associated with CAR-T cell therapy, leading to extreme caution and strong restrictions for on-study and commercial infusion of tisagenlecleucel in patients with active infection. CRS intervention with interleukin (IL)-6 blockade and/or steroid therapy was introduced late in the course during clinical trials due to concern for potential negative effect on efficacy and persistence. However, earlier CRS intervention is now viewed more favorably. Earlier intervention and consistency in management between providers may promote broader use of tisagenlecleucel, including potential curative therapy in patients who require remission and recovery of hematopoiesis for management of severe infection.Main body Patient 1 was diagnosed with B-ALL at 23 years old. Fourteen days before tisagenlecleucel infusion, the patient developed fever and neutropenia and was diagnosed with invasive Mucorales infection and BK virus hemorrhagic cystitis. Aggressive measures were instituted to control infection and to manage prolonged cytopenias during CAR-T cell manufacturing. Adverse events, including CRS, were manageable despite elevated inflammatory markers and active infection. The patient attained remission and recovered hematopoiesis, and infections resolved. The patient remains in remission ≥1 year postinfusion.Patient 2 was diagnosed with pre–B-ALL at preschool age. She developed severe septic shock 3 days postinitiation of lymphodepleting chemotherapy. After receiving tisagenlecleucel, she experienced CRS with cardiac dysfunction and extensive lymphadenopathy leading to renovascular compromise. The patient attained remission and was discharged in good condition to her country of origin. She remained in remission but expired on day 208 postinfusion due to cardiac arrest of unclear etiology.Conclusions Infusion was feasible, and toxicity related to tisagenlecleucel was manageable despite active infections and concurrent inflammation, allowing attainment of remission in otherwise refractory pediatric/young adult ALL. This may lead to consideration of tisagenlecleucel as a potential curative therapy in patients with managed active infections.Weijie LiKeith J AugustErin M HallDwight E YinRakesh K GoyalAtif A AhmedGrace S MitchellShawn D St. PeterTerrie G FlattIbrahim A AhmedRichard J HendricksonG Doug MyersBMJ Publishing GrouparticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENJournal for ImmunoTherapy of Cancer, Vol 9, Iss 1 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Weijie Li Keith J August Erin M Hall Dwight E Yin Rakesh K Goyal Atif A Ahmed Grace S Mitchell Shawn D St. Peter Terrie G Flatt Ibrahim A Ahmed Richard J Hendrickson G Doug Myers Tisagenlecleucel infusion in patients with relapsed/refractory ALL and concurrent serious infection
description	Background Tisagenlecleucel, an anti-CD19 chimeric antigen receptor T (CAR-T) cell therapy, has demonstrated durable efficacy and a manageable safety profile in pediatric and young adult patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) in the ELIANA pivotal trial and real-world experience. Experience from investigator-led studies prior to ELIANA suggests that infections and inflammatory conditions may exacerbate the severity of cytokine release syndrome (CRS) associated with CAR-T cell therapy, leading to extreme caution and strong restrictions for on-study and commercial infusion of tisagenlecleucel in patients with active infection. CRS intervention with interleukin (IL)-6 blockade and/or steroid therapy was introduced late in the course during clinical trials due to concern for potential negative effect on efficacy and persistence. However, earlier CRS intervention is now viewed more favorably. Earlier intervention and consistency in management between providers may promote broader use of tisagenlecleucel, including potential curative therapy in patients who require remission and recovery of hematopoiesis for management of severe infection.Main body Patient 1 was diagnosed with B-ALL at 23 years old. Fourteen days before tisagenlecleucel infusion, the patient developed fever and neutropenia and was diagnosed with invasive Mucorales infection and BK virus hemorrhagic cystitis. Aggressive measures were instituted to control infection and to manage prolonged cytopenias during CAR-T cell manufacturing. Adverse events, including CRS, were manageable despite elevated inflammatory markers and active infection. The patient attained remission and recovered hematopoiesis, and infections resolved. The patient remains in remission ≥1 year postinfusion.Patient 2 was diagnosed with pre–B-ALL at preschool age. She developed severe septic shock 3 days postinitiation of lymphodepleting chemotherapy. After receiving tisagenlecleucel, she experienced CRS with cardiac dysfunction and extensive lymphadenopathy leading to renovascular compromise. The patient attained remission and was discharged in good condition to her country of origin. She remained in remission but expired on day 208 postinfusion due to cardiac arrest of unclear etiology.Conclusions Infusion was feasible, and toxicity related to tisagenlecleucel was manageable despite active infections and concurrent inflammation, allowing attainment of remission in otherwise refractory pediatric/young adult ALL. This may lead to consideration of tisagenlecleucel as a potential curative therapy in patients with managed active infections.
format	article
author	Weijie Li Keith J August Erin M Hall Dwight E Yin Rakesh K Goyal Atif A Ahmed Grace S Mitchell Shawn D St. Peter Terrie G Flatt Ibrahim A Ahmed Richard J Hendrickson G Doug Myers
author_facet	Weijie Li Keith J August Erin M Hall Dwight E Yin Rakesh K Goyal Atif A Ahmed Grace S Mitchell Shawn D St. Peter Terrie G Flatt Ibrahim A Ahmed Richard J Hendrickson G Doug Myers
author_sort	Weijie Li
title	Tisagenlecleucel infusion in patients with relapsed/refractory ALL and concurrent serious infection
title_short	Tisagenlecleucel infusion in patients with relapsed/refractory ALL and concurrent serious infection
title_full	Tisagenlecleucel infusion in patients with relapsed/refractory ALL and concurrent serious infection
title_fullStr	Tisagenlecleucel infusion in patients with relapsed/refractory ALL and concurrent serious infection
title_full_unstemmed	Tisagenlecleucel infusion in patients with relapsed/refractory ALL and concurrent serious infection
title_sort	tisagenlecleucel infusion in patients with relapsed/refractory all and concurrent serious infection
publisher	BMJ Publishing Group
publishDate	2021
url	https://doaj.org/article/ebd8b85ed1f64889854a9550a505497f
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Tisagenlecleucel infusion in patients with relapsed/refractory ALL and concurrent serious infection

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