Disease- and Therapy-Specific Impact on Humoral Immune Responses to COVID-19 Vaccination in Hematologic Malignancies

Abstract

Coronavirus disease-19 (COVID-19) vaccine response data for patients with hematologic malignancy, who carry high risk for severe COVID-19 illness, are incomplete. In a study of 551 hematologic malignancy patients with leukemia, lymphoma, and multiple myeloma, anti–SARS-CoV-2 spike IgG titers and neutralizing activity were measured at 1 and 3 months from initial vaccination. Compared with healthy controls, patients with hematologic malignancy had attenuated antibody titers at 1 and 3 months. Furthermore, patients with hematologic malignancy had markedly diminished neutralizing capacity of 26.3% at 1 month and 43.6% at 3 months, despite positive seroconversion rates of 51.5% and 68.9% at the respective time points. Healthy controls had 93.2% and 100% neutralizing capacity at 1 and 3 months, respectively. Patients with leukemia, lymphoma, and multiple myeloma on observation had uniformly blunted responses. Treatment with Bruton tyrosine kinase inhibitors, venetoclax, phosphoinositide 3-kinase inhibitors, anti-CD19/CD20–directed therapies, and anti-CD38/B-cell maturation antigen–directed therapies substantially hindered responses, but single-agent immunomodulatory agents did not. Significance: Patients with hematologic malignancy have compromised COVID-19 vaccine responses at baseline that are further suppressed by active therapy, with many patients having insufficient neutralizing capacity despite positive antibody titers. Refining vaccine response parameters is critical to guiding clinical care, including the indication for booster vaccines, for this vulnerable population. See related article by Tamari et al., p. 577. This article is highlighted in the In This Issue feature, p. 549

How to Provide the Needed Protection from COVID-19 to Patients with Hematologic Malignancies

“…We reviewed the literature to gather information on the seroconversion rates after receiving a COVID-19 vaccine in patients with hematologic malignancies. We selected 18 series that provided anti-SARS-CoV-2 spike protein IgG seroconversion rates after full COVID-19 vaccination detailed by hematologic malignancy diagnosis, with at least 20 patients per group (Figure 1 and Supplemental Table 1) (2,(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19). The literature review also included six additional series that are not included in Figure 1, three due to sampling of serum antibodies before achieving full vaccination as evidenced by lower seroconversions in the healthy control group compared to the rest of the series (20,21), and three that did not provide breakdown of the data according to different histological diagnoses (22,23).…”

“…Important variables related to the hematologic malignancy, including being on active therapy, the type of therapy, being on watchful waiting before therapy, or having completed therapy, varied among the series and diagnoses. As a comparison, we provide the rates of seroconversion of healthy subjects from the series that included concomitant testing, which in some cases were age-matched controls (4,6,10,12,13,15,17,19,24). The combined healthy subjects group adds to 729 individuals, with seroconversion rates between 98-100% (Figure 1 and Supplemental Table 1), suggesting that these series adequately tested for anti-SARS-CoV-2 spike protein seroconversion at the time that healthy subjects would have responded to the vaccine.…”

“…Patients with chronic lymphocytic leukemia (CLL) have a particularly low rate of seroconversion after COVID-19 vaccination, ranging from 39% to 71% in the reported series (2,(5)(6)(7)(8)(9). A similarly low rate of seroconversion is evident in series reporting on patients with non-Hodgkin lymphoma (NHL), ranging from 42% to 75% (2,4,8,13,14,(16)(17)(18)(19)24). One series reported on patients with Waldenstrom macroglobulinemia (WM) with a 74% seroconversion rate (2).…”

“…One series reported on patients with Waldenstrom macroglobulinemia (WM) with a 74% seroconversion rate (2). These results of low seropositivity in some series while higher in others are likely to be related to the treatments that the patients were receiving at the time of analysis, and in particular the time since receiving therapy for the hematologic malignancy (13,25). For example, patients with NHL recently treated with anti-CD20 were less likely to develop serologic response to a COVID-19 vaccine, with the rate of seropositivity in one series being 3% in patients vaccinated within 45 days from the last anti-CD20 administration, increasing to 80% in patients vaccinated over one year after stopping this therapy (18).…”

“…Patients with multiple myeloma (MM) were reported to have a seroconversion rate between 65% and 95% (2,4,8,10,(12)(13)(14)(15). Variability in these series may be related to patient's age, level of hypogammaglobulinemia, number of lines of therapy for myeloma, and in particular being on treatment with an anti-CD38 antibody, anti-BCMA therapy, or corticosteroid therapy, all of which were significant factors resulting in lower seroconversion rates in the different series (8,10,12,13,15). Rates of COVID-19 vaccination response were close to healthy subjects in patients with acute leukemia, chronic myelogenous leukemia (CML), and myelodysplastic syndrome (MDS) (2,4,10).…”