Efficacy of COVID-19 Booster Vaccines in Patients with Hematologic Malignancies: Experiences in a Real-World Scenario

Abstract

Background: Two-dose COVID-19 vaccination often results in poor humoral response rates in patients with hematologic malignancies (HMs); yet responses to COVID-19 booster vaccines and the risk of COVID-19 infection post-booster are mostly uncertain. Methods: We included 200 outpatients with HMs and predominantly lymphoid neoplasms (96%, 191/200) in our academic center and reported on the humoral responses, which were assessed by measurement of anti-spike IgG antibodies in peripheral blood as early as 14 days after mRNA-based prime-boost vaccination, as well as factors hampering booster efficacy. Previous basic (double) immunization was applied according to the local recommendations with mRNA- and/or vector-based vaccines. We also report on post-booster COVID-19 breakthrough infections that emerged in the Omicron era and the prophylaxis strategies that were applied to poor and non-responders to booster vaccines. Results: A total of 55% (110/200) of the patients achieved seroconversion (i.e., anti-spike protein IgG antibody titer > 100 AU/mL assessed in median 48 days after prime-boost vaccination) after prime-boost vaccination. Multivariable analyses revealed age, lymphocytopenia, ongoing treatment and prior anti-CD20 B-cell depletion to be independent predictors for booster failure. With each month between anti-CD20-mediated B-cell depletion and booster vaccination, the probability of seroconversion increased by approximately 4% (p < 0.001) and serum−antibody titer (S-AbT) levels increased by 90 AU/mL (p = 0.011). Notably, obinutuzumab treatment was associated with an 85% lower probability for seroconversion after prime-boost vaccination compared to rituximab (p = 0.002). Of poor or non-responders to prime-boost vaccination, 41% (47/114) underwent a second booster and 73% (83/114) underwent passive immunization. COVID-19 breakthrough infections were observed in 15% (29/200) of patients after prime-boost vaccination with predominantly mild courses (93%). Next to seroconversion, passive immunization was associated with a significantly lower risk of COVID-19 breakthrough infections after booster, even in vaccine non-responders (all p < 0.05). In a small proportion of analyzed patients with myeloid neoplasms (9/200), the seroconversion rate was higher compared to those with lymphoid ones (78% vs. 54%, accordingly), while the incidence rate of COVID-19 breakthrough infections was similar (22% vs. 14%, respectively). Following the low frequency of myeloid neoplasms in this study, the results may not be automatically applied to a larger cohort. Conclusions: Patients with HMs are at a high risk of COVID-19 booster vaccine failure; yet COVID-19 breakthrough infections after prime-boost vaccination are predominantly mild. Booster failure can likely be overcome by passive immunization, thereby providing immune protection against COVID-19 and attenuating the severity of COVID-19 courses. Further sophistication of clinical algorithms for preventing post-vaccination COVID-19 breakthrough infections is urgently needed.

Keywords: COVID-19 booster vaccines; SARS-CoV-2; Sars-CoV-2 prophylaxis; hematologic malignancies; seroconversion.

Figure 1

Overview of all patients and entities included in this study. DLBCL, diffuse large cell B-cell lymphoma; HCL, hairy cell leukemia; SLL, small lymphocytic lymphoma; CLL, chronic lymphocytic leukemia; LPL, lymphoplasmocytic lymphoma; MCL, mantle cell lymphoma; MZL, marginal zone lymphoma; FL, follicular lymphoma.

Figure 2

Proportion of patients with and without seroconversion (anti-spike IgG antibodies to SARS-CoV-2 ≥ 100 AU/mL) after COVID-19 prime-boost vaccination.

Figure 3

(A) Seroconversion rates in relation to the time from last treatment (<3 months, 3–12 months, >12 months) in the anti-CD20 B-cell depletion group vs. the conventionally treated (cytotoxic treatment, targeted treatment, non-anti-CD20 immunotherapy) group. (B) Median antibody titer levels in accordance with the time from last treatment compared between the anti-CD20 lymphodepleted group vs. the conventionally treated (cytotoxic treatment, targeted treatment, non-anti-CD20 immunotherapy) group. (Seroconversion rate and median antibody titer levels of patients without treatment prior to prime-boost vaccination (watch and wait-strategy, n = 8) are not depicted.)

Figure 4

Comprehensive management of patients with hematologic malignancies according to serologic response (seroconversion) and anti-spike IgG titer levels after prime-boost vaccination.