Fatal breakthrough infection after anti-BCMA CAR-T therapy highlights suboptimal immune response to SARS-CoV-2 vaccination in myeloma patients
Author:
Aleman Adolfo, Van Oekelen OliverORCID, Upadhyaya Bhaskar, Agte Sarita, Kappes Katerina, Beach Katherine, Srivastava Komal, Gleason Charles R., Wang Bo, Mouhieddine Tarek H., Tuballes Kevin, Geanon Daniel, Khan Zenab, Gonzalez-Reiche Ana S., van Bakel HarmORCID, Simons Nicole W., Mouskas Konstantinos, Charney Alexander W., Rahman AdeebORCID, Kim-Schulze Seunghee, Sordillo Emilia M.ORCID, Krammer Florian, Cordon-Cardo Carlos, Bhardwaj Nina, Gnjatic Sacha, Merad Miriam, Brown Brian D., Sanchez Larysa, Chari Ajai, Jagannath Sundar, Simon Viviana, Wajnberg Ania, Parekh Samir,
Abstract
SUMMARYSevere 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.
Publisher
Cold Spring Harbor Laboratory
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