Impact of Pneumococcal Vaccination on Multiple Myeloma

Background. Streptococcus pneumoniae causes substantial morbidity and mortality from pneumonia, septicaemia and meningitis in myeloma primarilyrelated to severe hypogammaglobulinemia. In immunocompromised patients, pneumococcal vaccination is recommended as primeboost 13-valent conjugated vaccine (Prevnar13 ®) followed by 23-valent Pneumococcal polysaccharide (PS) vaccine (Pneumo23 ®) 1 to 2 months apart. However, there is a paucity of data in multiple myeloma (MM) to validate this approach.

We aimed at analyzing subclass and isotype (IgG, IgG2, IgA and IgM) specific responses to pneumococcal vaccination.

Method. We have prospectively included 28 NDMM. Serum was collected prior to vaccination and any treatment, then were sequentially collected at day 1 of each further cycle until treatment ended. 15 patients received both vaccinations Prevnar13® and Pneumo23® at the same time and 13 the prime boost. To assess the response to vaccination,VaccZyme™ (Binding Site) PCP anti-PS23 IgG, IgG2, IgA and IgM test was performed on every sample. In parallel, adverse events of infectious type were collected, with a particular attention topneumococcal infections.

Results. The median age was 66, the M/F ratio was 0.6. All patients, but one, presented with hypogammaglobulinemia at diagnosis, of whom 21 had severe hypogammaglobulinemia < 4g/L. Serum titers of IgG, IgG2, IgM and IgA anti-PS23 increased for 70%, 85%, 80% and 85% of the patients, respectively following vaccination, within a week response after vaccination for the majority of MM. Overall, 80% of the patient obtained significant antibody titres on at least one subtype and 55% for at least three subtypes. Ten patients underwent ASCT among whom eight had serum collected before and after ASCT. The anti-PS23 geometric mean titers significantly decreased when compared prior and after ASCT for IgG2 (49.4 to 11.7), IgA (56.3 to 2.9) and IgM (55.3 to 10.1) subtypes.

Among the 20 patients included into this study, 5 reached CR, 7 VGPR, 4 PR, 3 SD and 1 had PD. Our data showed that pneumococcal vaccine responses occurred independently of the degree of disease control, and thus did not correlate with the depth of response rate

Severe infection was observed in 5 patients, including two streptococcus oralis and one streptococcus salivarus septicemia (including one pneumonia and septicemia with S.oralis at diagnosis). No patient has presented Streptococcus pneumoniae infection.

Conclusion . Most patients respond to pneumococcal vaccination in MM, independently of depth of hypogammaglobulinemia, vaccine schemas, with no difference according to the disease control. However, there was a clear drop in serum vaccine titers following ASCT. This data tends to confirm that MM can respond to vaccination at diagnosis and relapse, but not if the patients are further immunocompromised with a myeloablative treatment approach.