Safety of CAR-T Cell Therapy in Asymptomatic Patients with Positive Respiratory Viral Testing Prior to CAR-T Infusions
Authors: Muenzen Reid M. , Chong Emeline R. , Therwhanger Dylan , Landsburg Daniel J. , Nasta Sunita D. , Svoboda Jakub , Barta Stefan K. , Hughes Mitchell E. , Weber Elizabeth , Ruella Marco , Frey Noelle V. , Porter David L. , Schuster Stephen J. , Chong Elise A. 
Published: December 2023

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.