Infections are still the most common cause of death for multiple myeloma besides the disease itself. Even at the MGUS stage, infection risk is already increased and with active disease, is even higher. For example, one study showed a 10x higher risk for viral infections and 7x higher risk for bacterial infections in multiple myeloma. In this article, European researchers share their suggestions for the logical use of vaccination to prevent infections in myeloma patients.  

Viral Infections

Varicella Zoster (Chickenpox and Shingles)

• Why: Patients treated with proteasome inhibitors, daratumumab, high dose steroids and stem cell transplant have higher risk of varicella zoster virus (VZV) reactivation. 
• What: It is not recommended to get the live vaccine. Use the use of the recombinant VZV glycoprotein E vaccine instead.
• When: 50-70 days after transplant. Patients should receive two doses 2–6 months apart. This strategy should be complemented by conventional prophylaxis with acyclovir or valaciclovir for further risk reduction.
• Who: This is of particular importance in patients receiving proteasome inhibitors, transplant or anti-CD38 antibodies. Especially helpful in the elderly.

Hepatitis A Virus

• Why: Hepatitis A can be contracted by traveling to international regions. 
• What: A vaccine to protect against hepatitis A. IVig also has some protection against hepatitis A.
• When: Patients should receive two doses given at least 6 months apart (6-12 months after transplant) to achieve long lasting protection, which can be attained in up to 95% of the general population. 
• Who: Patients traveling to endemic regions (Southeast Asia, Mediterranean countries, Africa, Middle and South America).

Hepatitis B Virus

• Why: If a patient lives in or travels to an area endemic for hepatitis B or patients with sexual partners with a chronic hepatitis B infection. 
• What: Use antiviral therapy. 
• When: In case of hepatitis B positivity and during anti-myeloma treatments when patients have significant T-cell immunosuppressive activity. Use for several months and preferably until after anti-myeloma therapy. Take 3 doses 6-12 months following transplant. 
• Who: Patients planned for therapy with proteasome inhibitors, immunomodulatory drugs, high-dose dexamethasone, monoclonal antibodies, and/or stem cell transplantation should be screened for hepatitis B by testing for HBs-Ag and anti-HBc antibodies. In case of negative HBs-Ag and positive anti-HBc results, patients should be tested for hepatitis B DNA. In patients without evidence of hepatitis B infection, no further action is needed unless the patient lives in, or travels to, areas endemic for hepatitis B or patients who have sexual partners with chronic hepatitis B infection.

Hepatitis C Virus

• Why: If a patient is immunosuppressed or has documented hepatitis C. 
• What: Patients with detectable disease documented by hepatitis C virus RNA should receive therapy with direct-acting antivirals, if possible before start of myeloma therapy. There is no hepatitis C vaccine today. 
• When: when highly immunosuppressed or when documented with hepatitis C. 
• Who: Patients who are highly immunosuppressed should be screened for hepatitis C. 

Measles, Mumps, and Rubella

• Why: MMR vaccines are routinely provided by most healthcare systems of developed countries. MMR vaccines can wane by 25% after 20 years of follow up in the general population.
• What: Live MMR vaccines. 
• When: 24 months following stem cell transplant or if patient lacks antibodies against these viruses. Current MMR vaccines are live and should not be used during the first 2 years following transplant.  
• Who: There are no reports that indicate that multiple myeloma patients are at greater risk than the general population. 

Bacterial Infections

Pneumococci

• Why: Pneumococcal infections are increased in myeloma patients. Over 90 types have been identified and two types of vaccines are commonly used to protect against these types. 
• What: The PCV13 (13-valent pneumococcal conjugate vaccine)
• When:  As both PCV13 and PPSV23 vaccine were found to protect against pneumococcal disease in the general population, patients should be vaccinated with PCV13 (in case of no previous PCV13 vaccination) followed by PCV23 after 2 months or an even longer interval. PPSV23 vaccination should be repeated in 5-year intervals but antibody response to a boost with PPSV23 may be lower than after primary vaccination.
• Who: All myeloma patients and especially the elderly.  

Haemophilus Influenzae (Not the Flu)

• Why: More than 50% of myeloma patients do not have antibodies to this pathogen. Blood activity against Hib is absent in 70% of myeloma patients. 
• What: A common bacterial pathogen that frequently colonizes the back of the nasal cavity. It can cause local infections, such as otitis media and sinusitis and can result in invasive disease, including pneumonia, meningitis, and sepsis.
• When: Ask your doctor if you should have this following myeloma treatment.
• Who: Should be considered in myeloma patients. One study showed antibody response in 71% of patients vaccinated after ASCT.

Meningococci

• Why: Low immune system levels and the diagnosis of myeloma are a well established risk factor for meningococcal disease. 
• What: Vaccines are available for clinical use. A conjugated tetravalent conjugated vaccine is recommended with an additional vaccine to target serogrup B. 
• When: 1-2 doses, 6-12 months after transplant
• Who: Should be considered in myeloma patients. One study showed antibody response in 71% of patients vaccinated after ASCT.

Diphteria, Pertussis, Tetanus, and Polio

• Why: Data on vaccinations for these diseases are scarce for myeloma patients. In other blood cancers, more patients lacked the antibodies against tetanus and diphtheria after intensive cancer treatment. 
• What: DPT, pertussis, tetanus and polio vaccines
• When: 3 doses, 6-12 months following transplant.
• Who: Myeloma patients following auto or allo transplant.

For a full table showing time frames for vaccination from the NCCN guidelines, click here. 

Autologous and Allogeneic Transplantation

Both autologous and allo transplant can lower protection against common diseases for myeloma patients. For those who have received an allogeneic transplant, it is recommended that they consider post-allo patients as in need for full revaccination.

Monoclonal antibodies, T-cell engagers (BiTEs), CAR-T cells

Some relapsed/refractory myeloma patients taking daratumumab show the same vaccination response to common vaccines as patients not taking a monoclonal antibody, so no specific information is available for patients using a monoclonal antibody. Patients using BiTEs or CAR-T cells are usually heavily pretreated and often have a compromised immune system. The researchers note that ideally, patients should be vaccinated before start of rescue therapy with the entire spectrum of vaccines listed with influenza, VZV, and vaccination against encapsulated bacteria (pneumococci, haemophilus influenzae, and meningococci) being most important.

Disease Status

If a patient has MGUS or Smoldering myeloma or is in remission and their immune system is fairly healthy, patients should be vaccinated with normal vaccines. According to the researchers:

Patients with scheduled chemotherapy should be vaccinated at least 2 weeks before initiation of chemotherapy, upon achievement of best response, 3–6 months after completion of chemotherapy or autologous transplantation, and 6–24 months after allogeneic transplantation. Vaccination with inactivated or live vaccines should not be given either before or about 3 months after treatment with intravenous immunoglobulin therapy because of concerns about effectiveness of vaccines.

Family Members and Close Friends

People in close contact to myeloma patients should receive all of their vaccines and especially influenza and pneumococci. There is a small risk of transferring live vaccines to patients (except for MMR). Healthcare workers should also receive appropriate vaccines. 

Precautions

Severely immunosuppressed patients should not receive live vaccines. Myeloma patients, if not in sustained well-controlled remission, are considered immunosuppressed, and thus are not candidates for life vaccines.

Vaccination should also be withheld in an individual who had a severe allergic reaction after a previous dose or vaccine component. Vaccination should be delayed in patients with uncontrolled disease, ongoing infections, or other acute illnesses.

Modern vaccines usually are very well tolerated. Local reactions, such as areas of redness, swelling, pain, and infrequently induration, may occur at the injection site. Such reactions may increase in severity with each subsequent injection. Very rarely, general reactions such as fever, chills, feeling tired, headache, muscle and joint aches are encountered.