Acquired Immunity in Patients with Multiple Myeloma Undergoing Maintenance Therapy Post-Autologous Hematopoietic Cell Transplantation

Maintenance therapy post-HCT for multiple myeloma is aimed to avoid relapse or delay disease progression. Immunizations are common practice to confer protection against vaccine-preventable infections during both early and late phases post-HCT. However, limited data on efficacy exist for patients undergoing maintenance therapy post-HCT.We performed this study to characterize the humoral and cellular responses to pneumococcal (PCV13) immunization post-HCT in patients undergoing maintenance therapy for multiple myeloma. Sixty patients, of which 52 received maintenance with an immunomodulatory (IMID) agent while 18 received a combination of an IMID and a proteasome inhibitor (PI), were immunized with PCV13 at 6, 8 and 12 months (mo.). Serotype-specific pneumococcal antibody concentrations as well as B- and T-cell distributions were determined pre-vaccination at 2, 6 mo. post-HCT and, 8, 12, and 14 mo. thereafter.Patients in both cohorts (IMID and IMID+PI) mounted a humoral response with a statistically significant difference between concentrations at 8, 12, and 14 mo. vs pre-vaccination baseline for all analyzed serotypes. No significant differences were observed in concentrations across all serotypes or in a time-dependent manner between the two cohorts. There were significant increases in concentrations over time from 8 to 14 mo. for serotypes 4, 23, and 26, while a significant decrease over time was observed for serotype 5. We did not observe a significant difference between arms at any time point in the proportion of patients protected against invasive or non-invasive pneumococcal disease. However, protective titers at 14 mo. were achieved in a significantly higher number of patients in the IMID cohort. No patients developed pneumococcal disease by 14 mo. after transplant. We observed no significant difference in the B effector and memory cell acquisition kinetics between treatment groups. Plasmablasts and activated memory B cell blood content peaked at 8 and 12 mo., respectively. Memory cell retention was the only marked difference between treatment arms with only IMID patients retaining circulating switched memory B cell (resting or activated) at 14 mo. (p=0.022). This suggests that while the type of maintenance therapy regimen might not affect acquisition of protective immunity in response to PCD13 vaccination, it may affect immunity retention. Immunization with PCV13 did not significantly alter effector and memory T cell compartments.Our study suggests that at both humoral and cellular levels, IMID +/- PI maintenance therapy post-HCT in multiple myeloma does not interfere with acquisition of protective immunity to PCV13. Past one year of maintenance though, doublet IMID+PI may limit retention of protective immunity to PCV13 compared to IMID only. This would need to be confirmed with a larger cohort of patients and potentially across other acellular vaccines.