Weaker Response to COVID-19 Vaccines After Hematopoietic Cell Transplantation or CAR T-Cell Therapy

The development of effective vaccines has been critical in limiting the transmission of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), and the importance of continued global vaccination programs cannot be overstated. Findings from several randomized trials have confirmed that vaccines are safe and effective in preventing severe coronavirus disease (COVID-19) in 66% to 95% of recipients. Since patients with hematological cancers, in particular those receiving hematopoietic cell transplantation (HCT) or chimeric antigen receptor T-cell (CAR-T) therapy are heavily immunocompromised, they are at an increased risk of severe and life-threatening COVID-19. Thus, they are considered as a high priority group for vaccination. According to the American Society of Hematology (ASH) and the American Society for Transplantation and Cellular Therapy (ASTCT) guidelines these patients could be offered the COVID-19 vaccine as early as three months after HCT or CAR-T therapy, although in general most vaccinations are recommended approximately 6 months after therapy to allow recovery of the immune system. However, the extent of the immune response to vaccines in these patients is unclear.

In an interesting, recently published ‘Letter to the Editor’ in Blood, findings from a single institution retrospective analysis of the serological response to COVID-19 vaccination in HCT and CAR-T therapy recipients were reported. The analysis included 130 patients with hematological cancers (45 had received autologous-[auto]-HC, 71 allogeneic [allo]-HCT, and 14 CAR-T therapy) who completed COVID-19 vaccination at least two weeks before their SARS-CoV-2 antibody levels were determined. An enzyme immunoassay (EUROIMMUN) was used to detect antibodies to the S1 domain of the SARS-CoV-2 spike protein in patients’ blood samples. Among 130 patients, 79 (60%) tested positive for SARS-CoV-2 antibodies, with a positivity rate of 60% for recipients of auto-HCT, 69% for allo-HCT and 21% for CAR-T therapy. Subgroup analysis showed no difference in seropositivity rates based on age, time between HCT and vaccination, disease type and IgG level in patients who had received auto-HCT. Similarly, in allo-HCT patients, the positivity rate was consistent across patient age, the interval between allo-HCT and vaccination, immunosuppression status, presence of active graft-versus-host-disease (GVHD), and recipient CD4 and CD8 counts at the time of vaccination. However, IgG levels were higher among allo-HCT seropositive patients than in those who were seronegative.  In addition, patients who had received corticosteroids for the treatment of GVHD had significantly lower seropositivity rates than those who had not received corticosteroids (31% versus 69%; P=0.001). Of note, for the minority of patients who had received vaccination less than 6 months post-therapy (n=19), seropositivity rates were 50%, 37% and 0% for auto-HCT, allo-HCT and CAR-T therapy, respectively.

Based on findings of weaker immune response in approximately one-third of patients who had received HCT and in 79% of patients after CAR-T therapy, the investigators concluded that these patients may be at a high risk of COVID-19 despite being vaccinated. Furthermore, it appears, although the data are limited, that response to vaccination is lower in patients who are vaccinated within 6 months of receiving HCT or CAR-T therapy. Therefore, additional measures, such as wearing masks, social distancing and vaccination of family members/households are vital.  Finally, they emphasize that further research is ongoing to elucidate the immunological response and the possible role of booster doses or revaccination for patients who fail to achieve an optimal immune response.

Dhakal B, et al. Blood 2021; Aug 4 [Online ahead of print].