SARS-CoV-2 vaccine safety and immunogenicity in patients with hematologic malignancies, transplantation, and cellular therapies

Abstract

Individuals with hematological malignancies and hematopoietic stem cell transplant (HCT) recipients are immunologically heterogenous groups with varying degrees of immunosuppression at increased risk of severe disease and mortality from SARS-CoV-2 infection. SARS-CoV-2 vaccines are key interventions to preventing severe COVID-19 and its complications. While these individuals were excluded from initial vaccine trials, there is now a growing body of acceptable safety and immunogenicity data among these individuals. A consistent signal for new or worsening graft versus host disease in allogeneic HCT recipients has not been demonstrated post-vaccination. Immunogenicity in these populations is variable depending on disease and treatment factors. However, serological responses may not accurately reflect vaccine protection as correlates of protection within these populations are not yet established. Large-scale studies powered to identify rare serious events, resolve differences in vaccine responses between different vaccination strategies, and identify immune correlates of protection within these populations are needed.

Keywords: COVID-19; Hematologic malignancies; SARS-CoV-2; Stem cell transplantation; Vaccines.

Fig. 1

Seropositivity frequency following SARS-CoV-2 vaccination in individuals with hematologic malignancy. Seropositivity frequencies in individuals with hematologic malignancy following one dose of ChAdOx1 or an mRNA-based SARS-CoV-2 vaccine (black bars) and after two doses of an mRNA-based or a single dose of Ad26.COV2.S vaccine (gray bars). Abbreviations: MM-multiple myeloma; HM-hematologic malignancy; CML-chronic myeloid leukemia; CLL-chronic lymphoid leukemia; MPM-myeloproliferative malignancy.

Fig. 2

Seropositivity frequency following SARS-CoV-2 vaccination in individuals with autologous or allogeneic stem cell transplant. Seropositivity frequencies in autologous stem cell (light gray) and allogeneic stem cell transplant (dark gray) recipients after SARS-CoV-2 vaccination. “1 dose” indicates seropositivity after a single dose of an mRNA-based vaccine or ChAdOx1 and “booster” indicates an mRNA-based vaccine following two doses of mRNA-based vaccine or two doses of ChAdOx1. All others are seropositivity following two doses of ChAdOx1 or mRNA-based vaccine, or single dose AD26COV2.S. Sherman et al. saw seropositivity as high as 80% depending on testing platform.

Fig. 3

Frequency of T-cell responses following SARS-CoV-2 vaccination in individuals with hematologic malignancy and cellular therapies. Frequencies of T-cell responses in individuals with hematologic malignancy (HM), allogeneic stem cell transplant (Allo), autologous stem cell transplant (Auto), or CAR-T cell therapy following SARS-CoV-2 vaccination. “After 1 dose” indicates T-cell response frequency after a single dose of BNT162b2 or ChAdOx1 and “after 2 doses” indicates T-cell response frequency after two doses of mRNA-based vaccine, ChAdOx1, or ChAdOx1 followed by BNT162b2. Lindemann et al. observed T-cell responses ranging from 12 to 29% depending on the spike protein peptide used in the assay.

Fig. 4

Seropositivity frequency following SARS-CoV-2 vaccination in individuals with CAR-T cell therapy. Seropositivity frequencies in individuals undergoing CAR-T cell therapy following vaccination with two doses of an mRNA-based vaccine (BNT162b2 or mRNA-1273) or one dose of Ad26.COV2.S.