Early immunomodulators with CAR T-cell immunotherapy in the COVID-19 era

Abstract

adjustment for all other known clinical risk factors did not affect the main outcome. Most importantly, the study presents a new locus with overt molecular relevance. However, the data must be verified in independent studies using a similar approach, and ideally in prospectively designed cohort studies. Further functional experiments using genetically modified animals could shed light on the protective role of rs708113 in WNT3A-WNT9A in hepatocarcinogenesis. Also, integrating the novel locus with previously known loci in PNPLA3, TM6SF2, and HSD17B13 to generate a polygenic risk score would be an attractive approach to test its utility in supporting clinical decisions. For that, it could be interesting to calculate the populationattributable risk of each locus individually, and in combination. This study is highly laudable and the key finding should stimulate others to address questions unanswered so far.We declare no competing interests.

Efficacy of a third SARS-CoV-2 mRNA vaccine dose among hematopoietic cell transplantation, CAR T cell, and BiTE recipients

“…Several factors, indigenous to CAR T recipients, may account for consistently blunted vaccine responses, including pre-existing, profound immunosuppression. Heavily pretreated status, often including prior HCT, lymphodepletion chemotherapy, bridging chemotherapy, prolonged B cell aplasia, preceding on-target off-tumor toxicities such as cytokine release syndrome, and immune effector cell-associated neurotoxicity syndrome requiring corticosteroids and tocilizumab may contribute to blunted vaccine responses ( Meir et al., 2021 , Abid, 2022 ).…”

Efficacy of SARS-CoV-2 primary and booster vaccine doses in CAR-T recipients – targeting the target antigen

“…The consequences of prolonged corticosteroids (cumulative exposure) on SARS-CoV-2 vaccine responses have been reported in patients with HM and those undergoing HCT (Supplementary Materials S10 ) [ 4 , 6 ]. Both corticosteroid and immunomodulator usage has consistently been demonstrated to increase the risk of infections while diminishing vaccine responses [ 12 ].…”

Immunologic responses to the third and fourth doses of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in cell therapy recipients: a systematic review and meta-analysis

“…Potential explanations for the persistently compromised immune responses to SARS-CoV-2 vaccines among CAR-T cell therapy recipients include pre-existing and robust immunosuppression, extended B cell aplasia, prior toxicities including cytokine release syndrome, and neurotoxicity syndrome requiring corticosteroids and tocilizumab. These conditions may contribute to the failure of the vaccines [51,52].…”