tetano
Editor, Senior Moderator
Pediatr Hematol Oncol
. 2022 Feb 9;1-9.
doi: 10.1080/08880018.2022.2035864. Online ahead of print.
Robust immune responses to SARS-CoV-2 in a pediatric patient with B-Cell ALL receiving tisagenlecleucel
Oren M Gordon[SUP] 1 [/SUP], Madeline Terpilowski[SUP] 2 [/SUP], Robin Dulman[SUP] 3 [/SUP], Michael D Keller[SUP] 1 2 [/SUP], Peter D Burbelo[SUP] 4 [/SUP], Jeffrey I Cohen[SUP] 5 [/SUP], Catherine M Bollard[SUP] 1 2 [/SUP], Hema Dave[SUP] 1 2 [/SUP]
Affiliations
Abstract
Recipients of anti-CD19 targeted therapies such as chimeric antigen receptor (CAR)-T cell are considered at high risk for complicated Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) infection due to prolonged B cell aplasia and immunosuppression. These patients represent a unique cohort and so far, immune responses to SARS-CoV-2 have not been well characterized in this setting. We report a pediatric patient with B-cell acute lymphoblastic leukemia (B-ALL) who had asymptomatic SARS-CoV-2 infection while receiving blinatumomab, followed by lymphodepletion (LD) and tisagenlecleucel, a CD19 targeting CAR-T therapy. The patient had a complete response to tisagenlecleucel, did not develop cytokine release syndrome, or worsening of SARS-CoV-2 during therapy. The patient had evidence of ongoing persistence of IgG antibody responses to spike and nucleocapsid after LD followed by tisagenlecleucel despite the B-cell aplasia. Further we were able to detect SARS-CoV-2 specific T-cells recognizing multiple viral structural proteins for several months following CAR-T. The T-cell response was polyfunctional and predominantly CD4 restricted. This data has important implications for the understanding of SARS-CoV-2 immunity in patients with impaired immune systems and the potential application of SARS-CoV-2-specific T-cell therapeutics to treat patients with blood cancers who receive B cell depleting therapy.
Keywords: CD19 directed therapy; SARS-CoV-2; T-cell response; chimeric antigen receptor; tisagenlecleucel.
. 2022 Feb 9;1-9.
doi: 10.1080/08880018.2022.2035864. Online ahead of print.
Robust immune responses to SARS-CoV-2 in a pediatric patient with B-Cell ALL receiving tisagenlecleucel
Oren M Gordon[SUP] 1 [/SUP], Madeline Terpilowski[SUP] 2 [/SUP], Robin Dulman[SUP] 3 [/SUP], Michael D Keller[SUP] 1 2 [/SUP], Peter D Burbelo[SUP] 4 [/SUP], Jeffrey I Cohen[SUP] 5 [/SUP], Catherine M Bollard[SUP] 1 2 [/SUP], Hema Dave[SUP] 1 2 [/SUP]
Affiliations
- PMID: 35135442
- DOI: 10.1080/08880018.2022.2035864
Abstract
Recipients of anti-CD19 targeted therapies such as chimeric antigen receptor (CAR)-T cell are considered at high risk for complicated Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) infection due to prolonged B cell aplasia and immunosuppression. These patients represent a unique cohort and so far, immune responses to SARS-CoV-2 have not been well characterized in this setting. We report a pediatric patient with B-cell acute lymphoblastic leukemia (B-ALL) who had asymptomatic SARS-CoV-2 infection while receiving blinatumomab, followed by lymphodepletion (LD) and tisagenlecleucel, a CD19 targeting CAR-T therapy. The patient had a complete response to tisagenlecleucel, did not develop cytokine release syndrome, or worsening of SARS-CoV-2 during therapy. The patient had evidence of ongoing persistence of IgG antibody responses to spike and nucleocapsid after LD followed by tisagenlecleucel despite the B-cell aplasia. Further we were able to detect SARS-CoV-2 specific T-cells recognizing multiple viral structural proteins for several months following CAR-T. The T-cell response was polyfunctional and predominantly CD4 restricted. This data has important implications for the understanding of SARS-CoV-2 immunity in patients with impaired immune systems and the potential application of SARS-CoV-2-specific T-cell therapeutics to treat patients with blood cancers who receive B cell depleting therapy.
Keywords: CD19 directed therapy; SARS-CoV-2; T-cell response; chimeric antigen receptor; tisagenlecleucel.