COVID‐19 after hematopoietic cell transplantation and chimeric antigen receptor (CAR)‐T‐cell therapy

Abstract

More than 3 years have passed since Coronavirus disease 2019 (COVID‐19) was declared a global pandemic, yet COVID‐19 still severely impacts immunocompromised individuals including those treated with hematopoietic cell transplantation (HCT) and chimeric antigen receptor‐T‐cell therapies who remain at high risk for severe COVID‐19 and mortality. Despite vaccination efforts, these patients have inadequate responses due to immunosuppression, which underscores the need for additional preventive approaches. The optimal timing, schedule of vaccination, and immunological correlates for protective immunity remain unknown. Antiviral therapies used early during disease can reduce mortality and severity due to COVID‐19. The combination or sequential use of antivirals could be beneficial to control replication and prevent the development of treatment‐related mutations in protracted COVID‐19. Despite conflicting data, COVID‐19 convalescent plasma remains an option in immunocompromised patients with mild‐to‐moderate disease to prevent progression. Protracted COVID‐19 has been increasingly recognized among these patients and has been implicated in intra‐host emergence of SARS‐CoV‐2 variants. Finally, novel SARS‐CoV2‐specific T‐cells and natural killer cell‐boosting (or ‐containing) products may be active against multiple variants and are promising therapies in immunocompromised patients.

Impact of COVID‐19 monoclonal antibodies on outcomes of COVID‐19 infection in hematopoietic stem cell transplant and chimeric antigen receptor therapy recipients

“…Current approaches underway include targeting new portions of the virus' receptor binding site (such as with the new broadly neutralizing MCA S728-1157), targeting evolutionarily conserved motifs that are not as readily mutated, and cocktails combining MCA with different targets (such as AZD5156, a combination of AZD3152 and AZD1061). 22,18,[40][41][42] Regardless of the mechanism, the development of MCA with activity against COVID-19 remains an important component in the provision of passive immunity against COVID-19 for HSCT and CAR-T recipients that are not as robustly served by active immunization, and who are at greater risk of severe complications without it.…”

Human herpesvirus-6, HHV-8 and parvovirus B19 after allogeneic hematopoietic cell transplant: the lesser-known viral complications

“…Testing of pre-HCT blood samples (or any sample in the donor) can help confirm iciHHV-6 when specific testing is unavailable. Testing for iciHHV-6 is warranted in cases with atypical presentation, high viral loads (often >10 5 -10 6 copies/ml in cellular samples in the absence of cytopenia), HHV-6A species and/or persistent detection not responding to therapy (>3 weeks or no decrease of viral load after >2 weeks of therapy) [50].…”

SARS-CoV-2 vaccination in the first year after hematopoietic cell transplant or chimeric antigen receptor T cell therapy: A prospective, multicenter, observational study (BMT CTN 2101)

“…Therefore, guidelines recommended SARS-CoV-2 re-vaccination as early as three months post-cellular therapy in the absence of real-world data (34,35). While knowledge is rapidly accumulating (36–39), the optimal timing, schedule of vaccination, and immunological correlates for protective immunity after cellular therapy are unknown. To address these knowledge gaps, the Center for International Blood and Marrow Transplant Research (CIBMTR) and Blood and Marrow Transplant Clinical Trials Network (BMT CTN) conducted a multi-center, prospective, observational study of the safety and immunogenicity of SARS-CoV-2 vaccination within 12 months after autologous HCT, allogeneic HCT, and CAR-T cell therapy.…”