This is the first in a series based on “Guidelines for screening and management of late and long-term consequences of myeloma and its treatment” published recently in the British Journal of Haematology. This is one of the most comprehensive resources we’ve found for overall recommendations for living with myeloma as more patients are living longer with the disease and the effects of long-term treatment.
The study aims to address the impact of the myeloma on the body, effects of treatment and the impact of treatment on psychological and social wellbeing. These “late effects” are described by the National Cancer Institute as:
‘[A] health problem[s]that occur[s]months or years after a disease is diagnosed or after treatment has ended. Late effects may be caused by cancer or cancer treatment. They may include physical, mental and social problems, and second cancers’(https://www.cancer.gov/dictionary).
With myeloma patients living longer than ever and many patients needing multiple lines of therapies, this type of study is needed more than ever. The disease, long-term treatment, combined with other health issues and the aging process places considerable physical and emotional demands on myeloma patients.
In this Part 1 article, we will focus on the topics of infection, immunity, drugs to prevent infection and vaccines.
Infection and Immunity in Myeloma
According to the article:
Myeloma causes profound immunodeficiency, which varies during the disease course and, for most patients, lasts lifelong. The immunodeficiency involves numerical and functional defects of B cells, T-cell subsets, natural killer cells, dendritic cells and, possibly, neutrophil function. This is compounded by the immunomodulatory effects of high-dose corticosteroids and novel agents, neutropenia and host factors, such as immobility.
Many myeloma patients die of infection-related causes and immunosuppression is directly related to disease activity (Table 1). Approximately 10% of patients die within 3 months of diagnosis and infections are often due to encapsulated bacteria such as phagocytosis, strep, and the flu. Other types of more rare infections like cytomegalovirus (CMV), Pneumocystis jirovecii, and cryptococcus are seen in late-stage, heavily treated patient. While most infectiosn are not fatal, they do have a major impact on quality of life.Myeloma timeline: periods of severe immunosuppression and associated common pathogens
|Period||Immunological effects||Common pathogens|
|At diagnosis and at times of aggressive relapse||Disease active; profound immunosuppression||Bacterial infections, especially Streptococcus pneumoniae,Haemophilus influenzae and Escherischia coli|
|Immediate post-autologous stem cell transplant period (c. 1 month)||Neutropenia||Bacteria associated with neutropenic sepsis|
|Recovery post autograft (up to c. 6 months)||Gradual reconstitution of T cell-mediated immunity||Pneumocystis jirovecii
HSV, VZV, CMV; rarely invasive fungal infection
|Remission||Immunity improved||Appropriate time for elective vaccinations
Re-vaccination schedule >6 months after autograft
|Multiple relapses, increasingly refractory disease||Progressive immunosuppression from underlying disease and multiple therapies||Bacteria as above, but in addition: progressive diminution in resistance to viral infections especially HSV, VZV, influenza, occasional atypical infections, e.g. aspergillus, CMV, cryptococcus|
Antibiotics and Other Anti-Infective Drugs
There is not enough data to suggest the regular use of antibiotics at any stage of myeloma, but they are regularly used post-transplant while patients are severely immuno-compromised and neutropenic. Pomalidomide treatment is associated with 23-30% risk of infection and it has been suggested that antibiotics could potentially be given for the first three months of therapy. According to the article:
Ciprofloxacin and enoxacin should be used with caution, as they can interact via cytochrome pathways, but levofloxacin, moxifloxacin, norfloxacin and ofoloxacin are safe.
Myeloma patients have a higher risk of viral infections, especially herpes zoster (shingles) and influenza. Proteasome inhibitors, immunomodulatory drugs (IMiDs) and high-dose corticosteroids increase this risk, particularly for reactivation of shingles. The reactiviation risk can be reduced by antiviral medication during bortezomib and lenalidomide treatment which should be continued for at least 6 weeks after stopping treatment. Physicians can consider indefinite acyclovir for patients with previous shingles (400 mg once daily) or if patients have renal issues, 200 mg once daily.
Invasive fungal infection is rare in myeloma but fungal infections of the mouth (thrush) can occur with prolonged corticosteroid therapy.
One way of boosting the immune system is for patients to receive IV immunoglobulins, but the data is not clear on how best to use these. They can increase levels of antibodies to common pathogens in myeloma patients but their use should be assessed in terms of infection history, comorbidities, the level of immunoglobulin reduction and failure to respond to vaccination. Immunoglobulins should be administered in accordance with national guidance (https://www.gov.uk/government/publications/clinical-guidelines-for-immunoglobulin-use-second-edition-update).
The response to all vaccines is typically reduced in myeloma patients and patient responses vary widely. However, there appears to be clinical benefit. Ideally, functional antibody levels should be used to measure response and inform further vaccination, but guidance in this area is lacking.
Common inactivated vaccines suitable for myeloma patients
Clear recommendations on the timing of vaccination are impossible through lack of data, but vaccinating a myeloma patient while on treatment or with active disease is likely to be less effective than during remission off therapy. Deferring vaccination may not be practical, e.g. seasonal flu vaccination, and may still have some efficacy.
Myeloma patients should only receive inactivated vaccines (Table 2). Live attenuated vaccines [Bacillus Calmette–Guérin (BCG), measles, measles/mumps/rubella (MMR), oral typhoid, herpes zoster, rubella, yellow fever] should be avoided.
It is recommended that all myeloma patients are vaccinated yearly against influenza. Consider vaccinating close household contacts with both the influenza and the varicella-zoster vaccine. It is recommended that myeloma patients receive the conjugate pneumococcal vaccine (PCV13), followed by the polysaccharide PPV23 at least 2 months later.
Those who have already received a single dose of PPV23 should be offered PCV13 at least 6 months after the PPV23, to reduce the risk of pneumococcal serotype-specific hyporesponsiveness. The Haemophilus influenzae type b vaccine (Hib) should also be considered.
Following autologous or allogeneic HSCT, patients are advised to follow a re-vaccination schedule according to the relevant guidelines for patients undergoing stem cell transplant.