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

  1. Adolfo Aleman
  2. Oliver Van Oekelen
  3. Bhaskar Upadhyaya
  4. Sarita Agte
  5. Katerina Kappes
  6. Katherine Beach
  7. Komal Srivastava
  8. Charles R. Gleason
  9. PVI study group
  10. Bo Wang
  11. Tarek H. Mouhieddine
  12. Kevin Tuballes
  13. Daniel Geanon
  14. Zenab Khan
  15. Ana S. Gonzalez-Reiche
  16. Harm van Bakel
  17. Nicole W. Simons
  18. Konstantinos Mouskas
  19. Alexander W. Charney
  20. Adeeb Rahman
  21. Seunghee Kim-Schulze
  22. Emilia M. Sordillo
  23. Florian Krammer
  24. Carlos Cordon-Cardo
  25. Nina Bhardwaj
  26. Sacha Gnjatic
  27. Miriam Merad
  28. Brian D. Brown
  29. Larysa Sanchez
  30. Ajai Chari
  31. Sundar Jagannath
  32. Viviana Simon
  33. Ania Wajnberg
  34. Samir Parekh

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Abstract

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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    SciScore for 10.1101/2021.05.15.21256814: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    No key resources detected.

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: Please consider improving the rainbow (“jet”) colormap(s) used on pages 32 and 29. At least one figure is not accessible to readers with colorblindness and/or is not true to the data, i.e. not perceptually uniform.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

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  2. Version published to 10.1101/2021.05.15.21256814v1 on medRxiv