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European Myeloma Network vaccine recommendations for multiple myeloma

Mar 26, 2021
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Patients with multiple myeloma (MM) have an increased risk of infections, due to disease-related immunosuppression coupled with the immunosuppressive effect of anti-myeloma therapy. It is therefore considered particularly important to vaccinate this patient population against frequently encountered pathogens. The National Comprehensive Cancer Network (NCCN) have recently published guidelines for COVID-19 vaccination in patients with hematologic malignancies, summarized on the Multiple Myeloma Hub.

Here, we provide a summary of the consensus recommendations for vaccination against other commonly encountered pathogens in patients with MM, published in Leukemia by the European Myeloma Network.1

Key recommendations

Recommended vaccines and dosing schedules for patients with MM are listed in Table 1. Because antibody responses to vaccination are often lower for MM patients than for the general population, measurement of postvaccination antibody titers and/or repeat vaccinations may be required.

Table 1. Recommendations for vaccination in patients with MM*

Viral pathogen

Vaccine type

Recommendation

Influenza 

Trivalent or quadrivalent

All patients with MGUS, SMM, MM, non-immune family members, close contacts and HCWs

2 doses within a 4-week interval if no documented antibody response to first dose; yearly

Before start of treatment and start of influenza season, or in a period of deep response to therapy

VZV

Recombinant VZV glycoprotein E vaccine

All patients

2 doses, 2–6 months apart

Live-attenuated VZV vaccine

All patients

4 doses

Hepatitis A

Inactivated hepatitis A vaccine

Patients traveling to endemic areas

2 doses, ≥ 6 months apart

Hepatitis B

Recombinant hepatitis B vaccine

Patients traveling to endemic areas, at risk of behavioral/occupational exposure, or on hemodialysis

3 doses

Bacterial pathogen

Vaccine type

Recommendation

Pneumococci

PCV13

All patients (if no prior PCV13 vaccination)

1 dose

PPV23

>2 months after PCV13

1–3 doses, repeat in 3 years

Hemophilus influenzae

Hib conjugate

Patients with asplenia; consider for all patients with MM

1 dose

Meningococci

Meningococcal conjugate

Patients with asplenia, complement deficiency, recurrent bacterial infections

1 dose

Diphtheria, tetanus, and pertussis

Diphtheria toxoid, tetanus toxoid, and acellular pertussis vaccine

Patients without primary DTP vaccination, or booster dose of tetanus and diphtheria toxoid vaccines

3 doses, booster dose of tetanus every 10 years

DTP, diphtheria, tetanus, and pertussis; Hib, Hemophilus influenza type B; MGUS, monoclonal gammopathy of undetermined significance; MM, multiple myeloma; PCV, pneumococcal conjugate vaccine; PPV, pneumococcal polysaccharide conjugate; SMM, smoldering multiple myeloma; VZV, varicella-zoster virus.
*Adapted from Ludwig, et al.1
Only if recombinant VZV glycoprotein E vaccine is not available

Treatment-based recommendations

After stem cell transplantation (SCT), particularly allogeneic SCT, patients have reduced antibodies to common pathogens and increased risk of viral reactivation, providing the rationale for a full vaccination program after autologous and allogeneic SCT with early childhood vaccinations, as well as vaccinations against influenza, varicella-zoster virus (VZV), pneumococci, Hemophilus influenzae, and meningococci.

  • For most pathogens, vaccination should be repeated at 4-week intervals.
  • It is recommended to administer most inactivated vaccines 6–12 months after SCT.
  • Live attenuated vaccines should not be administered during the first 2 years following transplantation.

Patients treated with monoclonal antibodies, bispecific T-cell engagers, or CAR T cells should be vaccinated before the start of therapy with all vaccines listed in Table 1, the most important being influenza, VZV, pneumococci, Hemophilus influenzae, and meningococci.

Timing of vaccination

It is reasoned that patients will benefit from being vaccinated when there is no or little immunosuppression, either during the stages of monoclonal gammopathy of undetermined significance or smoldering multiple myeloma before transformation into active MM, or during disease remission.

Patients with scheduled chemotherapy should be vaccinated:

  • ≥2 weeks before the start of chemotherapy treatment;
  • Upon achievement of a best response;
  • 3–6 months after completion of chemotherapy or autologous SCT;
  • 6–24 months after completion of allogeneic SCT; and
  • Not before, and ≥3 months after treatment with intravenous immunoglobulins.

Additional considerations:

  • Live vaccines should not be administered to patients who are severely immunosuppressed.
  • Vaccines should be postponed in patients with uncontrolled disease, ongoing infections, or other acute illnesses.

Vaccination of close contacts

Family members, healthcare workers and other close patient contacts should receive

  • all age- and exposure-appropriate vaccines;
  • vaccination against influenza;
  • vaccination against pneumococci if ≥65 years of age; and
  • revaccination with childhood vaccines in case of inadequate antibody response.

Healthcare workers should additionally be vaccinated against hepatitis B, and regularly against influenza.

Limitations

  • Most data used to inform these recommendations were generated before the introduction of new therapies that can cause deeper responses and reduce or even prevent immunosuppression.
  • Vaccine responses have mostly been assessed according to antibody titers alone, and not cellular immunity, so clinical protection is often assumed.
  • With limited data available from randomized trials, the recommendations are largely based on observational studies, clinical experience, and reports from expert committees.

Summary

These recommendations aim to provide an optimal vaccination strategy to prevent common infections that pose a significant risk for patients with MM.

  1. Ludwig H, Boccadoro M, Moreau P, et al. Recommendations for vaccination in multiple myeloma: a consensus of the European Myeloma Network. Leukemia. 2021;35:31-44. DOI: 1038/s41375-020-01016-0.

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