Clinical Characteristics and Outcomes of BCMA-Targeted CAR-T Cell Recipients with Coronavirus Disease 2019 during the Omicron Wave: A Retrospective Study

Background

Patients with relapsed/refractory multiple myeloma (R/R MM) are more susceptible to pathogens, including severe acute respiratory syndrome-coronavirus-2. And these patients are more likely to developing severe Coronavirus Disease 2019 (COVID-19) for their immunocompromised condition. Regardless the good response of B cell maturation antigen (BCMA)-targeted chimeric antigen receptor (CAR)-T cell therapy, the deficiency of humoral immunity after CAR-T cell infusion still threaten patients’ lives. However, with the decreasing of the COVID-19 severity and morality in Omicron wave, the characteristics and outcomes of BCMA-targeted CAR-T cell recipients with COVID-19 remain unknown. We conducted a comparative study to delineate the clinical characteristics and outcomes between recipients of BCMA-targeted CAR-T cell therapy who contracted COVID-19 and those who remained unaffected.

Methods

We retrospectively reviewed R/R MM patients who participated in BCMA-targeted CAR-T cell therapy at the First Affiliated Hospital of Zhejiang University School of Medicine (ChiCTR1800017404, NCT05430945). Patients who had performed antigen or quantitative polymerase chain reaction test for COVID-19 from November 2022 to February 2023 were included. The final follow-up time was on April 30, 2023, and patients should have been followed at least 60 days since COVID-19 diagnosis. The odds ratios for COVID-19 and severe COVID-19 were assessed using logistic regression analyses. The hazard ratios of COVID-19 survival and COVID-19 duration were estimated using Cox regression models.

Results

A total of 49 patients (30 male and 19 female) with R/R MM who had received BCMA-targeted CAR-T cell therapy at the First Affiliated Hospital of Zhejiang University School of Medicine were enrolled, consisting two cohorts: 17 patients without COVID-19 diagnosis, and 32 patients with COVID-19 diagnosis (including 26 with mild or moderate COVID-19 and 6 with severe COVID-19).

We found no significant factor associated with COVID-19 infection. Advanced age was regarded as a significant risk factor for developing severe COVID-19 (odds ratio (OR)=1.367, 95% confidence interval (CI)=1.017-1.838, P=0.038), while complete response (CR) after CAR-T cell therapy (OR=0.012, 95% CI=0.000-0.674, P=0.032) was a protective factor. In addition, male (hazard ratio (HR)=4.765, 95% CI=1.721-13.193, P=0.003) and CR after CAR-T cell therapy (HR=4.265, 95% CI=1.527-11.913, P=0.003) were associated with shorter duration of COVID-19. And CR after CAR-T cell therapy (HR=0.081, 95% CI=0.009-0.752, P=0.027) and non-CR stage of MM at the time of COVID-19 diagnosis (HR=4.610, 95% CI=1.259-16.879, P=0.003) were independent protective factor and risk factor for morality of COVID-19, respectively.

Conclusion

R/R MM patients who had received BCMA-targeted CAR-T cell therapy are more susceptible to COVID-19. However, COVID-19 severity and morality rate of this population reduced during Omicron pandemic. The risk factor for developing severe COVID-19 was older age and the protective factor was CR after CAR-T cell infusion. Moreover, male and CR after CAR-T cell therapy were significantly associated with shorter duration of COVID-19. And CR after CAR-T cell therapy was regarded as a protective factor, while non-CR stage of MM at the time of COVID-19 diagnosis was a risk factor. Thus, preventive strategies are vital for old, non-responsive patients with R/R MM.