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

Abstract

Smoldering multiple myeloma (SMM) is an asymptomatic clonal plasma cell disorder that frequently progress to multiple myeloma (MM), a disease at high risk of pneumococcal infections. Moreover, if the polysaccharide vaccine is poorly immunogenic in MM, the 13-valent conjugated vaccine has never been tested in clonal plasma cell disorders. We evaluated its immunogenicity for 7 serotypes in 20 patients ≥ 50 years of age with smoldering multiple myeloma (SMM) pre and post routine-vaccination with PCV13.Concentrations of IgG specific for 7 serotypes were measured at baseline, 1, 6, and 12 months after vaccination by standardized ELISA and an Opsonophagocytic Assay (OPA). The primary endpoint was the proportion of patients responding to at least 5 of the 7 serotypes by ELISA at one month.At 1 month post vaccination, 12 patients (60%) were responders by ELISA, among whom 8 were also responders by OPA. At 6 months, 6 (30% of total) of the 12 responders had persistent immunity, and only 2 (10% of total) at 12 months. These results suggested a partial response in this population and a rapid decrease in antibody levels in the first months of vaccination.Although one injection of the 13-valent pneumococcal conjugate vaccine is immunogenic in some patients with SMM, the response is transient. Repeated injections are likely to be needed for effective and sustained protection.

Recommendations for vaccination in multiple myeloma: a consensus of the European Myeloma Network

“…In one study, a response to PV23 vaccination before ASCT was noted in 33% of patients, with a response rate of 73% in those who achieved a CR [54]. Similarly, in another trial, higher antibody responses were reported in patients with well-controlled disease, but antibody titers decreased within few months in most patients [52], an observation reported in another series as well [55]. In MGUS, a high response rate to a PCV13 vaccine was found [56], and in one of these studies, a reasonable correlation between IgG antibody response to four serotypes and opsonophagocytic capacity, but this correlation was not seen in patients with MM [57], where IgG antibodies without opsonophagocytic capacity were observed as well [10].…”

Immunogenicity and safety of the 13-valent pneumococcal conjugate vaccine in patients with immunocompromising conditions: a review of available evidence

“… No SAEs were observed. Bahuaud et al 37 Immunogenicity (serotypes 4, 6B, 9V, 14, 18C, 19F, 23F only) of one dose of PCV13 in patients with MM Prospective cohort; immunogenicity evaluated 1, 6, and 12 months postvaccination France/Community hospital Pneumococcal vaccine-naive 20 62 (50‒74) At 1 month post-vaccination,12 (60%) patients were responders by IgG GMCs (>2-fold increase from baseline and >1 µg/mL antibody concentration) and eight were responders by OPA (>4-fold increase from baseline and titer ≥LLOQ). At 6 and 12 months, only six and two responders, respectively, had persistent immunity by OPA responder criteria.…”

“…In the first, patients with MM undergoing autologous HCT were given PCV13: two patients received three doses (pretransplant and at 7–10 and 21–24 d following transplant); three patients received two doses (pretransplant and at d 21 post-transplant); and one patient received a single dose (pretransplant). 36 , 37 All patients who received pre- and post-transplant PCV13 vaccinations showed significantly greater IgG antibody responses against vaccine-specific serotypes compared with nonvaccine serotypes. There was a significant increase in serotype-specific IgG levels when compared with prevaccination levels for 6 of the 11 serotypes tested (3, 4, 6B, 9V, 18C, 23).…”

“…Immunogenicity was assessed for PCV7 serotypes (4, 6B, 9V, 14, 18C, 19F, 23F) at 1 month, 6 months, and 12 months post-vaccination. 37 One month post-PCV13, 12 patients responded based on IgG levels measured in an enzyme-linked immunosorbent assay (ELISA; i.e., >2-fold increase in IgG antibody concentration and concentration ≥1 µg/mL for more than five serotypes) and eight patients responded based on OPA (titer greater than or equal to the lower limit of quantitation and 4-fold increase from baseline for more than five serotypes). When persistent immunity was assessed at 6 months postvaccination, seven patients were responders based on the ELISA (IgG) criteria and six based on OPA.…”

Response to PCV13 vaccination in patients with multiple myeloma versus healthy controls

“…7 Despite the fact that existing guidelines recommend vaccinating MM patients with PCV13, 8 there is paucity of data for this vaccination strategy. 9 We therefore compared the immune response to PCV13 in patients with MM versus normal controls. Our understanding of vaccine response will be crucial in establishing a successful, tailored approach to infection prevention, thereby further addressing a leading complication in these patients, and potentially decreasing associated morbidity and mortality.…”