Introduction.Active infection is a contraindication to CAR T-cell infusion (CAR-T). Our standard institutional practice (SOP) is to perform a respiratory virus panel (RVP) prior to CAR-T infusion; however, the risk of toxicity after CAR-T in the context of an asymptomatic, incidentally noted respiratory viral infection (+RVP) during pre-CAR-T testing is unclear. We report our institutional experience for asymptomatic patients (pts) with PCR evidence of viral respiratory presence who subsequently received CAR-T.

Methods.We retrospectively reviewed 306 pts with non-Hodgkin lymphomas who were treated at the Hospital of the University of Pennsylvania with commercial CAR-T products from 2018-2023. Per SOP, all pts had a PCR-based RVP test prior to lymphodepleting chemotherapy (LD); LD-CAR-T was delayed for at least 7 days for asymptomatic pts with +RVP. After 7 days, pts with continued +RVP can proceed to CAR-T if they remain asymptomatic. RVP included: adenovirus, non-SARS-CoV-2 coronavirus, human metapneumovirus, rhinovirus/enterovirus, influenza A/B, parainfluenza 1-4, respiratory syncytial virus A/B, with/without SARS-CoV-2. We selected pts who had a +RVP within 4 weeks of CAR-T and who were asymptomatic (without respiratory viral symptoms) at time of CAR-T infusion. Cytokine release syndrome (CRS) and neuro-toxicity domains defining immune effector cells (ICANS) were evaluated using ASTCT consensus grading. Any fever post-CAR-T without an alternative cause was considered CRS.

Results. We identified 15 pts with +RVP who were asymptomatic at the time of CAR-T: 12 (80%) were male; median age 54 years (range 38-75); 10 (67%) had large B-cell lymphoma; 4 (27%) follicular lymphoma; 1 (7%) mantle cell lymphoma; ECOG performance status (PS) ≤1 in 14 (93%); lactate dehydrogenase (LDH) elevated in 5 (33%); 14 (93%) received bridging therapy. Overall, 11 pts (73%) had rhinovirus/enterovirus, 1 (7%) had SARS-CoV-2, 1 (7%) had non-SARS-CoV-2 coronavirus, 1 (7%) had adenovirus, and 1 (7%) had RSV A.

Of these 15 pts with +RVP, 8 (53%) were asymptomatic at time of initial +RVP and 7 (47%) pts were symptomatic at time of +RVP. The median time of intial +RVP was 13 days before CAR-T; the median time of closest +RVP to CAR-T was 7 days prior to CAR-T. No patient who was asymptomatic with a +RVP developed symptoms between initial screening +RVP and CAR-T infusion. At the time of CAR-T infusion, all patients were asymptomatic and no patient required supplemental oxygen. CAR-T was administered outpatient in 9 pts (60%). Of 15 asymptomatic pts infused, 10 (67%) received tisagenlecleucel (tisa-cel), 2 (13%) axicabtagene ciloleucel (axi-cel), 2 (13%) lisocabtagene maraleucel (liso-cel), and 1 (7%) brexucabtagene autoleucel (brexu-cel). 8 of these 15 pts (53%) developed CRS (7 pts grades 1-2, one pt grade 3) and 4/15 (27%) ICANS (2 pts grades 1-2, 2 pts grades 3-4).

Of the 8 patients who remained asymptomatic and received CAR-T, 6 (75%) received tisa-cel, 1 (13%) axi-cel and 1 (13%) liso-cel. 5 of these 8 pts (63%) developed CRS (all grades 1-2) and 1/8 (13%) ICANS (grade 2). Of the 7 patients whose symptoms resolved prior to CAR-T but had +RVP, 4 (57%) received tisa-cel, 1 (14%) axi-cel, 1 (14%) liso-cel, and 1 (14%) brexu-cel. 3 of these 7 pts (43%) developed CRS (2 pts grades 1-2, 1 pt grade 3) and 3/7 (43%) ICANS (1 pts grades 1-2, 2 pts grades 3-4).

Discussion:In our experience, CAR-T in pts with PCR evidence of upper respiratory viral infection was generally safe in pts not requiring oxygen with a good PS who are asymptomatic or symptomatically resolved at time of CAR-T infusion. Rates of CRS and ICANS were comparable between asymptomatic pts and pts with resolved symptoms at time of CAR-T.

Landsburg:Morphosys: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; ADCT: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Epizyme: Membership on an entity's Board of Directors or advisory committees; Calithera: Membership on an entity's Board of Directors or advisory committees, Research Funding; Curis: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Other: Travel funding. Nasta:Ono Pharmaceutical: Research Funding; Genentech/Roche: Research Funding; Pharmacyclics: Research Funding; Accrotech: Honoraria; ADC Therapeutics: Honoraria; Merck-Data Safety Monitoring Committee: Membership on an entity's Board of Directors or advisory committees; Millennium Takeda: Research Funding; Loxo/Lilly: Research Funding; Raphael: Research Funding. Svoboda:SEAGEN: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; Incyte: Consultancy, Research Funding; Genmab: Consultancy; BMS: Consultancy, Research Funding; Atara: Consultancy; Astra Zeneca: Consultancy, Research Funding; Adaptive: Consultancy, Research Funding; ADCT: Consultancy; TG Therapeutics: Research Funding; Merck: Research Funding. Barta:Janssen: Consultancy; Acrotech: Consultancy; Affimed: Consultancy; Daiichi Sankyo: Consultancy. Ruella:GlaxoSmithKline: Consultancy; Beckman Coulter: Research Funding; AbClon: Consultancy, Research Funding; Bayer: Consultancy; viTToria biotherapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Scientific Founder, Research Funding; NanoString: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy. Frey:Sana Biotechnology: Consultancy; Kite Pharma: Consultancy. Porter:Angiocrine Bio: Membership on an entity's Board of Directors or advisory committees; Bluebird Bio: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Capstan Bio: Honoraria; DeCart: Membership on an entity's Board of Directors or advisory committees; Genentech: Current equity holder in publicly-traded company; Janssen: Membership on an entity's Board of Directors or advisory committees; Kite/Gilead: Membership on an entity's Board of Directors or advisory committees; Mirror Biologics: Membership on an entity's Board of Directors or advisory committees; National Marrow Donor Program: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding; Sana Therapeutics: Consultancy, Current equity holder in publicly-traded company; Tmunity: Patents & Royalties; Wiley and Sons Publishing: Honoraria. Schuster:Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Kite Pharmaceuticals: Consultancy; BeiGene: Consultancy, Honoraria; AstraZeneca: Consultancy, Honoraria; Janssen: Consultancy; Noardic Nanovector: Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria; Regeneron: Consultancy; Mustang Biotech: Consultancy; Morphosys: Consultancy; Loxo Oncology: Consultancy; Legend Biotech: Consultancy; Incyte: Consultancy, Honoraria; Genmab: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genentech/Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene/Juno Therapeutics: Consultancy, Research Funding; Caribou Biosciences: Consultancy, Membership on an entity's Board of Directors or advisory committees; AlloGene: Consultancy, Honoraria; Abbvie: Consultancy; viTToria biotherapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Fate Therapeutics: Membership on an entity's Board of Directors or advisory committees. Chong:MJH Healthcare Holdings, LLC: Honoraria; Genentech: Research Funding; Abbvie: Research Funding; Novartis: Honoraria; BMS: Honoraria; Beigene: Honoraria.

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