Predictors of Humoral Response to SARS-CoV-2 Vaccination after Hematopoietic Cell Transplantation and CAR T-cell Therapy

Abstract

Cellular therapies including allogeneic hematopoietic cell transplant (allo-HCT) and autologous hematopoietic cell transplant (auto-HCT) and chimeric antigen receptor (CAR) T-cell therapy render patients severely immunocompromised for extended periods after therapy, and data on responses to COVID-19 vaccines are limited. We analyzed anti-SARS-CoV-2 spike IgG Ab (spike Ab) titers and neutralizing Ab among 217 recipients of cellular treatments (allo-HCT, n = 149; auto-HCT, n = 61; CAR T-cell therapy, n = 7). At 3 months after vaccination, 188 patients (87%) had positive spike Ab levels and 139 (77%) had positive neutralization activity compared with 100% for both in 54 concurrent healthy controls. Time from cellular therapy to vaccination and immune recovery post-cellular therapy were associated with response. Vaccination against COVID-19 is an important component of post-cellular therapy care, and predictors of quantitative and qualitative response are critical in informing clinical decisions about optimal timing of vaccines and the requirement for booster doses.

Significance: Identifying predictors of response to vaccination against SARS-CoV-2 in patients following cellular therapy is critical to managing this highly vulnerable patient population. To date, this is the most comprehensive study evaluating quantitative and qualitative responses to vaccination, providing parameters most predictive of response and potentially informing booster vaccination strategies.See related article by Chung et al., p. 568. This article is highlighted in the In This Issue feature, p. 549.

Figure 1.

A, Scatter plot of anti–SARS-CoV-2 spike IgG Ab titers and neutralizing Abs. The red lines denote the thresholds for positive assays (anti–SARS-CoV-2, 50 AU/mL, neutralization Abs: 30% inhibition). The three groups of allo-HCT, auto-HCT, and chimeric antigen receptor (CAR) T-cell therapy are represented in this graph. B, Ab responses to COVID-19 vaccines according to type of cellular therapy and timing posttreatment. Anti–SARS-CoV-2 spike IgG and neutralizing Ab titers were measured at 3 months after initial COVID-19 vaccination and summarized using scatter plots with median and IQR. Left, plots comparing anti–SARS-CoV-2 spike IgG categorized according to time for cellular treatment and type of cellular treatment (auto-HCT, allo-HCT, CAR T) compared with healthy controls (HC). Green dashed line denotes the threshold for a positive result (50.0 AU/mL). Right, circulating neutralizing Abs against SARS-CoV-2 were assessed at 3 months after initial COVID-19 vaccination. Plots comparing neutralizing Abs categorized according to time for cellular treatment and type of cellular treatment (auto-HCT, allo-HCT, CAR T cell) compared with healthy controls. Green dashed line denotes the threshold for a positive result (30% inhibition). *, P < 0.05; **, P < 0.01; ***, P < 0.001. ns, not significant. Early allo, first year; mid-allo, 1 to 3 years; late allo, >3 years; early auto, first year; late auto, >1 year. The number of patients is reported for spike Ab (S) and neutralizing Ab (N) for each group: healthy control (S:63/N25), early auto (S:20/N15), late auto (S:41/N37), early allo (S:19/N14), mid-allo (S:55/N49), late allo (S:75/N61), and CAR (S:7/N2). C, Ab responses to COVID-19 vaccines according to immune recovery. Anti–SARS-CoV-2 spike IgG and neutralizing Ab titers were measured at 3 months after initial COVID-19 vaccination and summarized using scatter plots with median and IQR. Left, plots comparing anti–SARS-CoV-2 spike IgG among patients meeting immune recovery posttreatment (green) versus patients not meeting criteria (red). Green dashed line denotes the threshold for a positive result (50.0 AU/mL). Right, circulating neutralizing Abs against SARS-CoV-2 were assessed at 3 months after initial COVID-19 vaccination. Plots comparing neutralizing Abs among patients meeting immune recovery posttreatment (green) versus patients not meeting criteria (red). Green dashed line denotes the threshold for a positive result (30% inhibition). **, P < 0.01; ***, P < 0.001. Pos, meeting all criteria, i.e., CD4⁺ T-cell count >200 cells/μL, CD19⁺ B-cell count >50 cells/μL, IgG >500 mg/dL, and PHA mitogen proliferation >40%). Neg S:52/N43, Pos S:52/N52.