Vaccination Remains Essential in Multiple Myeloma Despite Impaired Responses

Infections remain one of the leading causes of morbidity and mortality in patients with multiple myeloma (MM), largely due to the profound immunosuppression caused by both the disease and its treatments. A recent review published in the European Journal of Haematology highlights that although vaccine responses are often impaired, immunization still provides measurable benefits, reducing respiratory infections, hospitalizations, and pneumonia in patients with MM.¹

Underlying immune dysfunction is central to infection risk. MM leads to hypogammaglobulinemia, impaired T- and B-cell function, and defects in dendritic and natural killer cells. High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) deepens this vulnerability, producing long-lasting lymphodepletion. B-cell recovery may take more than a year, and CD4+ T-cell reconstitution is often slower, leaving patients unable to mount effective immune responses to pathogens or vaccines.

A Swedish study of 9253 patients confirmed infections to be a leading cause of morbidity and mortality in MM. Another study found nearly half of patients experienced at least 1 infection in the year before therapy, and 2 in 5 developed another within the first 6 months of treatment. Respiratory infections, most commonly due to influenza and Streptococcus pneumoniae, were consistently linked to hospitalization, clinical decline, and treatment delays.

Despite impaired immunogenicity, studies show vaccination still provides protection. In one study, influenza immunization in MM patients on chemotherapy reduced lower respiratory infections by 61% and hospitalizations by 83%. High-dose and adjuvanted formulations further improve immune responses and have been associated with more durable protection.^2,3

Pneumococcal disease remains a particularly severe threat in patients with MM. In a Canadian study, the annual incidence of invasive pneumococcal disease (IPD) was 673.9 per 100,000 in MM compared with 11.0 per 100,000 in the general population (OR, 62.8; 95% CI, 39.6-99.8; P < .001). The 13-valent pneumococcal conjugate vaccine (PCV13) and the 23-valent polysaccharide vaccine (PPSV23) remain standard in MM, although protective antibodies develop in only about 33% to 40% of patients with PPSV23 and up to 58% with a 3-dose PCV13 regimen post-transplant. Responses are strongest when vaccination is done before ASCT or during remission.

A recent expert consensus panel strongly endorsed sequential use of PCV13 followed by PPSV23 to maximize serotype coverage and improve immunogenicity, noting that vaccines should be tailored "to the patient's treatment phase and immune status, while promoting greater awareness among healthcare providers to overcome barriers to vaccine uptake." An overall response rate of 44.4% has been reported with the 3-dose PCV20 in transplant patients, noting that PCV20 was associated with stronger immunogenicity against several serotypes regardless of baseline immune status or treatment, while PCV21, approved in 2024, demonstrated robust immunogenicity across 21 serotypes, including 11 not previously covered.

Other key vaccines include recombinant zoster (Shingrix, RZV), recommended particularly in patients receiving proteasome inhibitors or after ASCT, and has demonstrated durable efficacy in immunocompromised populations. Hepatitis B vaccination is recommended for all seronegative patients. However, because seroconversion rates are often below 50%, high-dose regimens and repeated vaccine dosing may be required. Other inactivated vaccines, including those for Haemophilus influenzae type B, tetanus, diphtheria, pertussis, and meningococcus, are considered safe and appropriate in MM, especially around transplant.

COVID-19 vaccines have demonstrated variable efficacy, with patients treated with anti-CD38 or BCMA-targeted therapies often mounting weak humoral responses, making booster doses and passive immunization with monoclonal antibodies necessary. Regular revaccination is recommended due to waning neutralizing antibody levels and emerging variants.

For patients receiving CAR T-cell therapy or bispecific antibody therapies, vaccination should occur before treatment, with revaccination considered after immune recovery. Live vaccines shouldn't be used in this group for at least 2 years post-therapy.

"By addressing key challenges and proposing evidence-based solutions, we seek to support more effective and personalized immunization strategies for individuals living with MM," the authors noted, also emphasizing that while immunogenicity is often reduced, vaccination remains indispensable in MM.¹ They add that "Looking forward, the integration of immune profiling, expanded use of adjuvanted formulations, and novel platforms such as mRNA-based vaccines could help reshape the vaccination landscape for this high-risk population."

References

1. Martino EA, Vigna E, Bruzzese A, et al. Vaccination in multiple myeloma: challenges and strategies. Eur J Haematol. Published online July 26, 2025. doi:10.1111/ejh.70013
2. van Aalst R, Russo EM, Neupane N, et al. Comparing the impact of high-dose versus standard-dose influenza vaccines on hospitalization cost for cardiovascular and respiratory diseases: Economic assessment in the US Veteran population during 5 respiratory seasons using an instrumental variable method. Vaccine. 2021;39(Suppl 1):A51-A55. doi:10.1016/j.vaccine.2020.05.080
3. Hall VG, Smibert OC, Sullivan SG, et al. Influenza vaccination strategies in patients with hematologic cancer. N Engl J Med. 2025;392(3):306-308. doi:10.1056/NEJMc2406750