COVID-19 and hematopoietic stem cell transplantation and immune effector cell therapy: a US cancer center experience

Maurer, Katie; Saucier, Anna; Kim, Haesook T.; Acharya, Utkarsh; Mo, Clifton C.; Porter, Julie; Albert, Cindy; Cutler, Corey; Antin, Joseph H.; Koreth, John; Gooptu, Mahasweta; Romee, Rizwan; Wu, Catherine J.; Soiffer, Robert J.; Nikiforow, Sarah; Jacobson, Caron A.; Ho, Vincent T.

doi:10.1182/bloodadvances.2020003883

Cited by 27 publications

(33 citation statements)

References 30 publications

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“…Another study from Dana-Farber Cancer Institute examined outcomes in 127 cell therapy patients treated during the initial COVID-19 surge, including 27 CAR-T recipients. During the study period, 1 patient with DLBCL contracted COVID-19 fifty-one days after receiving tisa-cel and died due to COVID-19–related complications 121 days after CAR-T infusion 24 .…”

Section: Covid-19 Outcomes In Cellular Therapy Recipientsmentioning

confidence: 99%

State of the CAR-T: Risk of Infections with Chimeric Antigen Receptor T-Cell Therapy and Determinants of SARS-CoV-2 Vaccine Responses

Meir

Abid

2021

Transplantation and Cellular Therapy

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Chimeric antigen receptor T-cell (CAR-T) therapy has shown unprecedented response rates in patients with relapsed/refractory (R/R) hematological malignancies. While CAR-T therapy renders hope to heavily pre-treated patients, the rapid commercialization and cumulative immunosuppression predispose patients to infections for a prolonged period. CAR-T poses distinctive short- and long-term toxicities and infection risks among patients who receive CAR-T after multiple prior treatments, often including hematopoietic cell transplantation. The acute toxicities include cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome. The long-term B-cell depletion, hypogammaglobulinemia, and cytopenia further predispose patients to severe infections and abrogate the remission success achieved by the living drug. These on-target-off-tumor toxicities deplete B-cells across the entire lineage and further diminish immune responses to vaccines. Early observational data suggest that patients with hematologic malignancies may not mount an adequate humoral and cellular response to SARS-CoV-2 vaccines. In this review, we summarize the immune comprising factors indigenous to CAR-T recipients. We discuss the immunogenic potential of different SARS-CoV-2 vaccines based on the differences in the manufacturing platforms among CAR-T recipients. Given the lack of data related to the safety and efficacy of SARS-CoV-2 vaccines in this distinctively immunosuppressed cohort, we summarize the infection risks associated with FDA-approved CAR-T constructs and the potential determinants of vaccine responses. The review further highlights the potential need for booster vaccine dosing and the promise for heterologous prime-boosting in CAR-T recipients.

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Section: Covid-19 Outcomes In Cellular Therapy Recipientsmentioning

confidence: 99%

State of the CAR-T: Risk of Infections with Chimeric Antigen Receptor T-Cell Therapy and Determinants of SARS-CoV-2 Vaccine Responses

Meir

Abid

2021

Transplantation and Cellular Therapy

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“…Nonetheless, in certain clinical scenarios, postponing transplantation or cellular therapy can negatively affect the prognosis of the malignancy [ 15 , 16 ]. Therefore, even though health systems are overwhelmed with COVID-19 patients and despite the increased risk of complications with cellular therapies, HCT and CAR-T therapy have continued to be performed around the globe [ 17 , 18 ]. Patients undergoing HCT/CAR-T are required to be asymptomatic and to test negative for SARS-CoV-2 before conditioning chemotherapy [19] .…”

Section: Introductionmentioning

confidence: 99%

Impact of SARS-CoV-2 in Hematopoietic Stem Cell Transplantation and Chimeric Antigen Receptor T Cell Therapy Recipients

Mushtaq

Shahzad

Chaudhary

et al. 2021

Transplantation and Cellular Therapy

103

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Coronavirus disease 2019 (COVID-19), a respiratory illness caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was declared a pandemic in March 2020, and has caused more than 600,000 deaths in the United States at the time of this report. Hematopoietic stem cell transplantation (HCT) or chimeric antigen receptor T cell (CAR-T) therapy recipients have a higher risk of mortality with COVID-19 owing to profound immune dysregulation. In this study, we investigated the impact of SARS-CoV-2 in HCT/CAR-T therapy recipients. This single-center prospective study included all (n = 58) adult HCT/CAR-T recipients who were diagnosed with COVID-19 at the University of Kansas Medical Center between March 2020 and May 2021. Baseline and disease-related characteristics were ascertained from medical records. Data were analyzed using SPSS version 21 (IBM, Armonk, NY). Bivariate analyses, using the chi-square and t-test, and logistic regression analyses were conducted. The study included 58 HCT/CAR-T patients who acquired SARS-CoV-2 infection, including recipients of allogeneic HCT (n = 32), autologous HCT (n = 23), and CAR-T therapy (n = 3). The median patient age was 58 years (range, 24 to 77 years), and 64% were males. The median time from HCT/CAR-T therapy to SARS-CoV-2 infection was 17.7 months (range, 0.2 to 201.9 months), and 22% of the patients acquired SARS-CoV-2 within the first 100 days post-HCT/CAR-T therapy. The primary hematologic disorders were plasma cell (36%), myeloid (38%), and lymphoid (26%) malignancies. Myeloablative conditioning was performed in 62% of patients. Donors were autologous (45%), matched sibling (15%), matched unrelated (21%), and haploidentical (19%). Prior history of grade II-IV acute graft-versus-host disease (GVHD), active GVHD, and current immunosuppressive therapy (IST) was noted in 22%, 31%, and 36% of patients, respectively. Concurrent infections were observed in 19%. Lymphopenia ( P = .049) and high serum ferritin concentration ( P = .020) were associated with mortality. COVID-19 severity was mild in 50% of the patients, moderate in 22%, and severe in 28%. Clinical findings included pneumonia or abnormal chest imaging (in 50%), hypoxia (28%), intensive care unit admission (19%), and mechanical ventilation (10%). Therapies included remdesivir (in 41%), convalescent plasma (35%), dexamethasone (22%), monoclonal antibodies (19%), and tocilizumab (3%). The median duration of viral shedding (positive SARS-CoV-2 PCR) was 7.7 weeks (range, 2 to 18.7 weeks), and 2 patients had a persistent infection for >5 months post-CAR-T therapy. After a median follow-up of 6.1 months (range, 0.5-13.6 months), the mortality rate was 16% in all patients and 28% in allogeneic HCT recipients. Among 9 patients who died, the median survival after SARS-CoV-2 infection was 23 days (range, 14 to 140 days). In survivors with moderate-severe COVID-19, the median time to recovery was 4.2 weeks (range, 1.1 to 24.7 weeks). Among allogeneic HCT...

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“…Apart from this incident, Maurer et al . 21 did not find any differences in 100-day overall survival, progression-free survival, and rates of non–COVID-19 infections when compared with patients from the pre-pandemic era. Due to these positive results, Maurer et al .…”

Section: Available Literaturementioning

confidence: 63%

A review on recipients of hematopoietic stem cell transplantation patients with COVID-19 infection

Sahu

Siddiqui

2021

Therapeutic Advances in Infection

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For the last few months, various geographical regions and health sectors have been facing challenges posed by the current COVID-19 pandemic. COVID-19 has led to significant disruption in the normal functioning of potentially life-saving therapies of hematopoietic cell transplant and chimeric antigen receptor therapy. As transplant physicians are gaining more information and experience regarding the undertaking of these complex procedures during the ongoing COVID-19 pandemic, we believe it is important to discuss the challenges faced, prognostic risk factors, and outcomes of COVID-19 in post-hematopoietic stem cell transplantation patients based on the available real-world data.

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COVID-19 and hematopoietic stem cell transplantation and immune effector cell therapy: a US cancer center experience

Cited by 27 publications

References 30 publications

State of the CAR-T: Risk of Infections with Chimeric Antigen Receptor T-Cell Therapy and Determinants of SARS-CoV-2 Vaccine Responses

State of the CAR-T: Risk of Infections with Chimeric Antigen Receptor T-Cell Therapy and Determinants of SARS-CoV-2 Vaccine Responses

Impact of SARS-CoV-2 in Hematopoietic Stem Cell Transplantation and Chimeric Antigen Receptor T Cell Therapy Recipients

A review on recipients of hematopoietic stem cell transplantation patients with COVID-19 infection

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