Invasive Pneumococcal Disease May Unmask Undiagnosed Blood Cancers, Antibody Deficiencies in Adults

A severe pneumococcal infection may be the first clinical clue to an undiagnosed B-cell malignancy or antibody deficiency in adults, according to a prospective, multicenter study published in Scientific Reports. Among 156 adults hospitalized with invasive pneumococcal disease (IPD) in Sweden, 7 were subsequently diagnosed with a hematologic cancer and 12 with monoclonal gammopathy of undetermined significance (MGUS).^1,2

Immunoglobulins (Ig) are essential for clearing invading pneumococci, but serum protein and Ig testing is not routinely performed after a single IPD episode, according to the investigators from the University of Gothenburg. As a result, patients with an underlying B-cell disorder or immunodeficiency are rarely identified in this setting.^1,2

The investigators enrolled adults with culture- or PCR-confirmed IPD at 3 hospitals in Region Västra Götaland between 2018 and 2023. Patients had a median age of 70 years, and pneumonia was the most common manifestation (84%), followed by meningitis (11%). Blood samples were collected during acute infection (n = 153) and again 2 to 4 months later in the convalescent phase (n = 76). A total of 64 age- and sex-matched individuals without IPD served as controls.¹

M Protein Detected in 1 in 4 Patients During Infection

Monoclonal Ig, or M protein, was detected in 27% of patients (41 of 153) during acute infection compared with 4.7% of controls (P < .001). After excluding 10 patients with a previously known hematologic malignancy, M protein remained present in 22% of patients (31 of 141; P = .002). After adjustment for age, sex, and predisposing conditions, patients with IPD had nearly 8-fold higher odds of M protein detection than controls (adjusted OR, 7.96; 95% CI, 2.22-28.52).¹

In 7 patients, the M protein was transient and no longer detectable during convalescence. Among the 19 patients with persistent M protein, 7 were diagnosed with a B-cell malignancy, including multiple myeloma (n = 4), Waldenström macroglobulinemia (n = 2), and mantle cell lymphoma (n = 1). The remaining 12 patients were diagnosed with MGUS, a prevalence of 8.3% among those without a known malignancy compared with 4.7% among controls.¹

Tor Härnqvist, a doctoral student at the University of Gothenburg, infectious disease physician at NU Hospital Group, and co-lead author, noted that because these tests are not standard after severe pneumococcal infection, "we may miss patients with undiagnosed blood cancer or immunodeficiency," along with the opportunity to begin treatment.²

Antibody Deficiencies Persist After Recovery

Nearly half of patients (44%) sampled during acute infection and 34% sampled during convalescence had at least 1 Ig isotype or IgG subclass below the lower limit of the reference interval, compared with 16% of controls. During convalescence, levels of IgA, IgG2, or IgG4 were low in 16% to 20% of patients vs 0% to 2% of controls. IgG2 is of particular concern, as it makes up a major share of the antibodies that target encapsulated bacteria such as pneumococci.¹

Follow-up evaluation identified primary Ig deficiency in 3 patients, and 7 patients started Ig replacement therapy, including several with secondary immunodeficiency related to a known hematologic malignancy or prior rituximab treatment. Circulating B-cell counts also remained below the reference interval in 40% of patients 2 to 4 months after infection, compared with 13% of controls. Because Ig levels can drop during acute infection, the authors noted that low values in this phase should be confirmed after recovery.¹

The investigators acknowledged several limitations. Only 37% of eligible patients enrolled, about half provided convalescent samples, and controls were not hospitalized and had fewer comorbidities. Serum free light chains were also not assessed, which may have led to underdetection of light-chain MGUS.1

Implications for Vaccination and Pharmacy Practice

The findings carry implications for pneumococcal immunization. Pneumococcal vaccination is recommended for patients with MGUS, but high M protein concentrations are associated with weaker vaccine responses, underscoring the value of earlier MGUS diagnosis.¹

The CDC currently recommends a pneumococcal conjugate vaccine (PCV15, PCV20, or PCV21) for all adults aged 50 years or older who have never received a conjugate vaccine or whose history is unknown. If PCV15 is used, a dose of PPSV23 should follow 1 year later, with a minimum 8-week interval considered for adults with immunocompromising conditions.³

Co-lead author Karin Bergman, a doctoral student and infectious disease physician at Södra Älvsborg Hospital, noted that serotypes covered by the Swedish childhood vaccine have declined sharply but have been largely replaced by nonvaccine serotypes. These frequently affect older adults and those with cancer or compromised immune systems. Bergman said adult vaccine recommendations should account for which vaccines are used in children and which serotypes circulate as a result.²

For pharmacists, the study reinforces the importance of reviewing pneumococcal vaccination status in older adults and in patients with known or suspected immunocompromising conditions. The study authors concluded that M protein and Ig assessment could be considered after an IPD episode, though larger studies are needed to confirm which patients benefit most.¹

REFERENCES

1. Härnqvist T, Bergman K, Mellgren Å, et al. Invasive pneumococcal disease unmasks monoclonal immunoglobulins and antibody deficiencies: a multicenter prospective study in adults. Sci Rep. 2026;16:23203. doi:10.1038/s41598-026-61992-8

2. Pneumonia can reveal undiagnosed blood cancer. News release. EurekAlert! September 30, 2026. Accessed October 1, 2026. https://www.eurekalert.org/news-releases/1146014

3. Pneumococcal vaccine recommendations. CDC. Updated February 25, 2026. Accessed October 1, 2026. https://www.cdc.gov/pneumococcal/hcp/vaccine-recommendations/index.html