Assessment of Anti-Bacterial Antibodies in Multiple Myeloma Patients at Disease Presentation and in Response to Therapy: Implication for Patient Management

Introduction

Multiple myeloma is associated with severe immunodeficiency and immunoparesis (a reduction in normal polyclonal immunoglobulin levels below the lower limit of normal) is a well-established feature of this haematological malignancy. Bacterial infections are a major cause of the high early death rate that occurs in newly diagnosed myeloma patients. In particular, patients are more likely to contract a pneumococcal infection than the healthy population. Immunoparesis may contribute to increased susceptibility to bacterial infections; however, the prevalence and depth of suppression of specific antibodies against common bacterial pathogens has yet to be characterised in a large myeloma patient cohort. This study investigated functional antibodies levels at disease presentation and in response to induction treatment in the UK Tackling Early Morbidity and Mortality in Myeloma trial (TEAMM).

Method

Serum samples at disease presentation and after 12 weeks of induction therapy from 890 multiple myeloma patients (aged 35-90 years old) enrolled in TEAMM were analysed by Multiplex Luminex assay for IgG antibody levels against 19 bacterial antigens: 12 pneumococcal (Pn), 4 meningococcal (Men), haemophilus influenza b (HiB) polysaccharide, and diphtheria and tetanus toxoids. Protective antibody levels were: 0.35 μg/mL for Pn serotypes, 2 μg/mL for Men serotypes, 1 μg/mL for HiB polysaccharide, and 0.1 IU/mL for diphtheria and tetanus. Antibody levels from patients with myeloma were compared to healthy blood donors (n = 193, aged <65 years).

Results

A significantly lower proportion of myeloma patients demonstrated protective levels against all bacterial antigens compared to the healthy donors (p < 0.05) (see Table attached). At disease presentation, less than 6% of multiple myeloma patients had serum IgG antibodies above the WHO 0.35µg/ml protective threshold for at least 8 of the 12 investigated Pn serotypes. Additionally, before treatment, < 20%, 21%, 40% and 13% of patients exhibited protective levels of anti-Men serotypes, HiB polysaccharide, tetanus and diphtheria antibodies respectively.

A higher proportion of patients aged < 65 years old were protected against Men serotypes, HiB and tetanus compared to those aged ≥ 65 years. Conversely, a higher proportion of patients in the ≥ 65 age group were protected against Pns serotypes compared to those aged < 65, reflecting the polysaccharide Pn vaccination (PPV23) programme in the UK for those aged 65 or over (see Table attached).

Following induction therapy, serum IgGs levels against all investigated bacteria were significantly lower than presentation levels (p < 0.01) (see Figure attached).

Discussion

This is the first study to show anti-bacterial antibody levels are severely compromised in a large population of multiple myeloma patients. The investigation based on age revealed valuable insights into the efficacy of the current UK Pn vaccination programme in older adults, with over 65 years old vaccinated patients demonstrating higher anti-Pn antibody levels compared to their younger unvaccinated counterparts. However, the overwhelming majority of patients still failed to meet protective levels. Additionally, 12 weeks of anti-myeloma treatment significantly reduced antibody levels against bacterial pathogens even further. These findings highlight the importance of protecting patients from bacterial infection during induction therapy, using strategies such as antibiotic prophylaxis, and provide evidence on the need for an immunisation programme for myeloma patients during remission.

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