Poor Correlation between Pneumococcal IgG and IgM Titers and Opsonophagocytic Activity in Vaccinated Patients with Multiple Myeloma and Waldenstrom's Macroglobulinemia

Abstract

e Patients with multiple myeloma and other B cell disorders respond poorly to pneumococcal vaccination. Vaccine responsiveness is commonly determined by measuring pneumococcal serotype-specific antibodies by enzyme-linked immunosorbent assay (ELISA), by a functional opsonophagocytosis assay (OPA), or by both assays. We compared the two methods in vaccinated elderly patients with multiple myeloma, Waldenstrom's macroglobulinemia, and monoclonal gammopathy of undetermined significance (MGUS). Postvaccination sera from 45 patients (n ‫؍‬ 15 from each patient group) and 15 control subjects were analyzed by multiplexed OPA for pneumococcal serotypes 4, 6B, 14, and 23F, and the results were compared to IgG and IgM antibody titers measured by ELISA. While there were significant correlations between pneumococcal OPA and IgG titers for all serotypes among the control subjects (correlation coefficients [r] between 0.51 and 0.85), no significant correlations were seen for any of the investigated serotypes in the myeloma group (r ‫؍‬ ؊0.18 to 0.21) or in the group with Waldenstrom's macroglobulinemia (borderline significant correlations for 2 of 4 serotypes). The MGUS group resembled the control group by having good agreement between the two test methods for 3 of 4 serotypes (r ‫؍‬ 0.53 to 0.80). Pneumococcal postvaccination IgM titers were very low in the myeloma patients compared to the other groups and did not correlate with the OPA results. To summarize, our data indicate that ELISA measurements may overestimate antipneumococcal immunity in elderly subjects with B cell malignancies and that a functional antibody test should be used specifically for myeloma and Waldenstrom's macroglobulinemia patients.

Immunogenicity and persistence of the 13-valent Pneumococcal Conjugate Vaccine (PCV13) in patients with untreated Smoldering Multiple Myeloma (SMM): A pilot study

“…These nonfunctional antibodies may be able to bind to polysaccharide coated on a plate and thus be positive on ELISA, but are not able to opsonize whole bacteria [28] . Interestingly, a recent paper found a good correlation between ELISA and OPA after pneumococcal vaccine in MGUS but not in MM patients [24] . In our hands as in MGUS patients, we found a good correlation between ELISA and OPA in SMM patients (supplementary data), except for baseline with only 2 serotypes (14 and 18C) on the seven tested which had good correlations between the two tests ( Fig.…”

“…To our knowledge, this study is the first to evaluate the immunogenicity of pneumococcal vaccination in SMM patients. Pneumococcal vaccines have been evaluated in MGUS and in MM patients [ 24 , 25 ]. However, SMM patients differ from MM patients as they have no evidence of end-organ damage and/or other myeloma-defining events.…”

Managing hypogammaglobulinaemia secondary to haematological malignancies in Australia and New Zealand: a clinician survey

“…Criteria and guidelines for Ig replacement vary internationally . For example, British, but not Australian, criteria require a trial of prophylactic antibiotics and pneumococcal vaccination before Ig replacement, although no randomised trials prospectively assessing this strategy have been reported, and vaccine responses are impaired in secondary hypogammaglobulinaemia …”

Multiple Myeloma Baseline Immunoglobulin G Level and Pneumococcal Vaccination Antibody Response

“…8 Consistent with our pilot findings, Karlsson and colleagues showed that total IgG antibody response does not correlate with functional assays of pneumococcal killing. 5 Thus, from this limited data, it appears that clinicians should not rely on quantitation of IgGs nor their subclasses when deciding whether or not to vaccinate patients with MM. Circles -Controls Diamonds -Patients Our study has several limitations, for example, small sample size, sample dropouts and a heterogeneous subject population.…”

“…Antibody response of a doubling in immunoglobulin G (IgG) and immunoglobulin M antibody titers has been historically used as a metric of response, but in general this has not been clinically validated. 5 Many clinicians may not comply with recommendations for pneumococcal pneumonia vaccination (PV) because of a perception that MM and other cancers of the immune system inherently are accompanied by immunologic compromise, especially in the setting of reduced IgG levels. We hypothesized that total IgG levels and levels of IgG subclasses might predict responsiveness to PV.…”