Fatal breakthrough infection after anti-BCMA CAR-T therapy highlights suboptimal immune response to SARS-CoV-2 vaccination in myeloma patients
Preprint
- 15 May 2021
- preprint
- Published by Cold Spring Harbor Laboratory
Abstract
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.Keywords
This publication has 15 references indexed in Scilit:
- Low neutralizing antibody responses against SARS-CoV-2 in older patients with myeloma after the first BNT162b2 vaccine doseBlood, 2021
- Suboptimal response to COVID-19 mRNA vaccines in hematologic malignancies patientsmedRxiv, 2021
- Idecabtagene Vicleucel in Relapsed and Refractory Multiple MyelomaThe New England Journal of Medicine, 2021
- SARS-CoV-2 Vaccines in Patients With Multiple MyelomaHemaSphere, 2021
- Cellular Immunity in COVID-19 Convalescents with PCR-Confirmed Infection but with Undetectable SARS-CoV-2–Specific IgGEmerging Infectious Diseases, 2021
- Safety and Efficacy of the BNT162b2 mRNA Covid-19 VaccineThe New England Journal of Medicine, 2020
- Correlates of protection against SARS-CoV-2 in rhesus macaquesNature, 2020
- Recommendations for vaccination in multiple myeloma: a consensus of the European Myeloma NetworkLeukemia, 2020
- How I vaccinate blood and marrow transplant recipientsBlood, 2016
- Executive Summary: 2013 IDSA Clinical Practice Guideline for Vaccination of the Immunocompromised HostClinical Infectious Diseases, 2014