Fatal breakthrough infection after anti-BCMA CAR-T therapy

 

Fatal COVID-19 breakthrough infection case after unspecified mRNA vaccine


Fatal breakthrough infection after anti-BCMA CAR-T therapy highlights suboptimal immune response to SARS-CoV-2 vaccination in myeloma patients

Adolfo Aleman, Oliver Van Oekelen, Bhaskar Upadhyaya, Sarita Agte, Katerina Kappes, Katherine Beach, Komal Srivastava, Charles R. Gleason, PVI study group, Bo Wang, Tarek H. Mouhieddine, Kevin Tuballes, Daniel Geanon, Zenab Khan, Ana S. Gonzalez-Reiche, View ORCID ProfileHarm van Bakel, Nicole W. Simons, Konstantinos Mouskas, Alexander W. Charney, View ORCID ProfileAdeeb Rahman, Seunghee Kim-Schulze, VEmilia M. Sordillo, Florian Krammer, Carlos Cordon-Cardo, Nina Bhardwaj, Sacha Gnjatic, Miriam Merad, Brian D. Brown, Larysa Sanchez, Ajai Chari, Sundar Jagannath, Viviana Simon, Ania Wajnberg, Samir Parekh
Mount Sinai Hospital 78 Icahn School of Medicine 79 One Gustave L. Levy Place, Box 1185 80 New York, NY 10029
doi: https://doi.org/10.1101/2021.05.15.21256814

SUMMARY


Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are highly effective in healthy individuals. Patients with multiple myeloma (MM) are immunocompromised due to defects in humoral and cellular immunity as well as immunosuppressive therapies. The efficacy after two doses of SARS-CoV-2 mRNA vaccination in MM patients is currently unknown. Here, we report the case of a MM patient who developed a fatal SARS-CoV-2 infection after full vaccination while in remission after B cell maturation antigen (BCMA)-targeted chimeric antigen receptor (CAR)-T treatment. We show that the patient failed to generate antibodies or SARS-CoV-2-specific B and T cell responses, highlighting the continued risk of severe coronavirus disease 2019 (COVID-19) in vaccine non-responders. In the largest cohort of vaccinated MM patients to date, we demonstrate that 15.9% lack SARS-CoV-2 spike antibody response more than 10 days after the second mRNA vaccine dose. The patients actively receiving MM treatment, especially on regimens containing anti-CD38 and anti-BCMA, have lower antibody responses compared to healthy controls. Thus, it is of critical importance to monitor this patient population for serological responses. Non-responders may benefit from ongoing public health measures and from urgent study of prophylactic treatments to prevent SARS-CoV-2 infection.


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In another study of patients from Cleveland clinic, of 1696 IMIDS patients on B cell depleting therapies 74 developed breakthrough COVID-19. Outcomes were severe with 24 (35%) hospitalized, 11 (15%) patients requiring critical care and 6 (8 %) deaths.

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