Infection Prophylaxis Including Vaccination
For the Consensus Panel 1
Elias Anaissie, MD.
Myeloma Institute for Research & Therapy
Little Rock, AR, USA
Paris, May 3-6, 2011
Infection Prophylaxis including Vaccination
for MM Patients
Outline
1.Vaccines
1. Key points
2.Which vaccines; when to vaccinate; Vaccinate close contacts.
3.Assessing response to vaccination.
4.Travel vaccines.
2. Immunoglobulin replacement
1. Potential candidates
2. Optimal dosage-schedule; Duration of therapy
3. Route of administration; post exposure prophylaxis (VZV)
3. Antimicrobial prophylaxis
1. Risk stratification
2.Antimicrobial agents
4.Other preventive methods
Indications for vaccination in
multiple myeloma
Indications for Vaccination in MM
Key Points
1. Efficacy:
Limited but one can take advantage of partial protection.
Vaccination of close contacts strongly recommended .
2. Gaps in knowledge:
Very few studies in MM patients /None with the novel agents.
Trials with clinical endpoint (i.e. infections) lacking.
No efficacy data for influenza virus vaccine (live).
No safety data for influenza (live), varicella, zoster vaccines.
Key Points
Inactivated = Safe
Avoid Live
Influenza virus
Vaccines
-Influenza (intranasal)
-MMR
-Varicella
-Zoster
-Polio (oral) [alternative]
-BCG
-Yellow fever
Unless
-MGUS, Smoldering or
- Remission and
> 6 mos after end chemo
Live
WHICH
Risk factors for invasive disease:
VACCINE?
Defects in humoral immunity
Immunosuppressive therapies
Streptococcus
Renal failure / nephrotic syndrome
pneumoniae
Asplenia, DM, COPD, CHF
PPSV23 recommended by the CDC.
23-valent
polysaccharide
Repeat in 3 -5 years.
(PPSV23)1
Alternative strategy:
3 doses of PCV 13 + 1 dose PPSV23 at 12
13-valent conjugate
months to broaden immune response or a
(PCV13 )
4th.PCV dose if severe immunocompromise
Antibiotics
If infection despite vaccination, use
antibiotic prophylaxis based on local
1. MMWR 1997;46(RR-8)
epidemiology: penicillin or fluoroquinolone.
2. MMWR 2000;49(RR-10
3. www.cdc.gov
WHICH
2010-2011: only 1 vaccine, not 2.
VACCINE?
Vaccine strains:
l Same A/California/7/2009-like H1N1
2010-11
l New A. H3N2 strain for North Hemisphere
Influenza
l B. was in 2009-10 seasonal vaccine
Vaccine
All 3 worldwide this season.
HD-fluzone (Sanofi-Pasteur):
High-Dose
Increased x 4 amount of viral
Inactivated
antigen vs. other TIVs1,2
Influenza
Up to 80% higher antibody titers
Vaccine for
to Flu A vaccine strains vs.
65 Years1
standard-dose for 65 y.o. +/-
1.MMWR; 59(16);485-86, 2010.
underlying medical conditions2
2.Keitel, W. A. et al. Arch Intern Med ;
166 (10): 11217, 2006.
3.Falsey A. et al. J Infect Dis. 200:
Antiviral prophylaxis may be needed
172-180, 2009
WHICH
1. HBsAg (+) close contacts.
VACCINE?
2. Travel to areas of high endemicity.
Hepatitis B
3. Behavioral/occupational exposure.
Recombinant
4. Chronic liver / renal disease.
Vaccine
1. May test 1 month after last dose,
then every 6-12 mos.
2. Consider revaccinating nonresponders,
preferably after the cause for non-
responsiveness has resolved.
3. Booster if titer falls to <10 IU/L.
4. May retest every 4-5 years.
WHEN TO
1. INDIVIDUALIZE
VACCINATE? Risks / benefit assessment
l Individual's susceptibility to infection
l Institution / country guidelines.
No
2. ASAP (MGUS, smoldering myeloma).
Perfect
3. For patients scheduled for chemo
Timing!
14 days before initiation of chemo
Before stem cell mobilization
6 months after completion of chemo
6-12 months after Auto-Transplant
Upon achievement of best response
4. Useful?Lymph/CD4, uninvolved s-Igs
1. All non-immune close contacts:
VACCINATE
Influenza (+healthcare workers)
CLOSE
CONTACTS
2. Only those at risk:
Hepatitis A : travel to areas of high
endemicity, behavioral and occupational
exposure, chronic liver disease
Hepatitis B: same + ESRD/hemodialysis
Polio
Live vaccines
Tetanus, diphtheria, pertussis
·Avoid direct contact
Meningococcus : younger & military.
with patients for 4- 6
weeks after vaccines. 1. Live vaccines for close contacts:
·But individualize
MMR :> 1 y.o., not pregnant or Immunosupp.
(personal condition,
institution/country
Varicella : same + negative/uncertain H/O
guidelines) .
varicella and negative serostatus.
Assessing Serologic Response
1. Surrogate marker for protection (level and/or duration).
2. Relatively simple and inexpensive for Hep. B and tetanus.
3. May not be feasible for others b/o several limitations:
Large technical variability, costs, availability.
Serologic response to a polysaccharide (PS) Ag. does not
imply responsiveness to all PS Ags. Same for protein Ags.
Evaluation of responsiveness to S. pneumoniae: measure 14
serotypes to pneumo. PSs (but titers to serotypes conjugate
vaccine not relevant to PS responsiveness).
Travel Vaccines
Based on Host and Travel Itinerary
Vaccine performance
Vaccine type
Risk
Effective and safe
Influenza § , HBV,
Endemic,
HAV, polio (inactive), other
rabies, meningococcus,
Japanese encephalitis
Effective,
Yellow fever
Endemic
Not safe (live)
Moderately effective,
BCG, Typhoid (oral) Endemic,
Not safe (live)
other
§ Travel to southern hemisphere (April -Sept.); food/water; STD
Data re: safety / efficacy of some vaccines in ICH lacking.
IVIG/SCIG: when vaccination contraindicated or insufficient
time to develop immunity, IVIG/SCIG may provide protection
against measles, mumps, rubella, hep. A/B, varicella, rabies.
Immunoglobulin Replacement
to Prevent Infections in
Patients with Myeloma
IMMUNOGLOBULIN Gaps in knowledge:
REPLACEMENT
IVIG prevented serious infection
Gaps in knowledge
during the plateau phase of myeloma.
However, no antibiotic prophylaxis,
Potential candidates
and mildly immunosuppressive chemo.
No level of s-Ig shown protective.
No data exist to support their role
with novel agents or the optimal
dosage-schedule/duration of therapy.
Selected candidates:
Against IVIG:
Significant hypogammaglobulinemia +
·Gaps in knowledge
·Cost
Serious infections despite vaccination
& antimicrobial prophylaxis +
·Effective antibiotics
·Renal toxicity
Infection likely to respond to IVIG
IMMUNOGLOBULIN 1. Optimal dosage-schedule:
REPLACEMENT
Gaps in knowledge
Dosage schedule
Dose schedule which keeps patient
free from serious infections.
Duration of therapy Trough IgG level > 400 mg/dL?
Not practical; IgG MM; excessive use
1. Duration of therapy:
1. Gaps in knowledge
2. INDIVIDUALIZE:
1. Risks / benefits
2. Lymphocyte/CD4, uninvolved s-
Ig, remission status, ongoing
immunosuppressive therapies.
3. A 6 mo trial then stop & assess rate
of serious infections.
INTRAVENOUS (IVIG):
IMMUNOGLOBULIN
REPLACEMENT
Half-life ~ 3 weeks
Routes:
1-10 days in HSCT pts, fever, infection.
Intravenous
Well tolerated /rate-related reactions
Subcutaneous
Acute renal failure (sucrose-containing)
IgA-depleted if congenital deficiency
Local IVIG products recommended.
SUBCUTANEOUS (SCIG) :
·Premedicate
As effective as IVIG for infection
-Acetaminophen
-Diphenhydramine
Fewer systemic reactions/tolerated by
most pts with reactions to IVIG.
-Glucocorticoids
Safe in most IgA-deficient pts.
·Hydrate
·Slow rate
Convenient (self-infuse/ no IV access)
·Monitor
More consistent s-IgG levels
Post Exposure Prophylaxis for Varicella/Zoster
1. Determine the risk following exposure:
1. Pt susceptible? (bortezomib, no vaccination & no H/O
varicella) All immunocompromised pts with H/O varicella
can be considered immune, except HSCT recipients.
2. Exposure significant enough to result in infection ?
(prolonged face-to-face or close indoor contact 1 h)
3. Higher risk for complications (severe immunosuppression)?
2. Post-exposure prophylaxis:
1. Varicella/Zoster
1.
Acyclovir
2.
VariZIG IM within 96 h or 1 dose of IVIG (400 mg/kg)
2. Hepatitis A / B
Infection Prophylaxis in
Patients with Myeloma
Infection Prophylaxis
Risk Stratification
PATHOGEN EXPOSURE
ION
dz
Ig
MM
(HSCT)
liver
Severe immunosuppression
HD-steroid
-ANC< 100/L; > 14 days
normal
(ESRD)++
DM,
-ALC< INFECTION
dose
300/L; CD4 <200/L
of
years
HSCT,
cell
severe
refractory
- sIg (uninvolved)
DYSFUNCTION
·Smoking
IMMUNOSUPPRESS
/
·>70
failure
Rx;
34+
·GHVD,
overload,
production
CD
ORGAN
·Renal
·Iron
STATE
·
·Relapsing
GENETIC FACTORS
ET
Extensive
·Small
N
·
1. Bacterial infections:
Prophylactic
Neutropenic:
Regimens of
1.
levofloxacin
Antimicrobial
Non-neutropenic:
Agents
1.
TMP/SMX or amoxicillin
2. Fungal infections:
1. Oral thrush: Fluconazole/clotrimazole
2. P. jiroveci: Bactrim or dapsone
3. Viral infections:
1. HSV/VZV: acyclovir or valacyclovir
2. Influenza viruses:
1.
Neuraminidase inhibitors (if high-risk)
Preventive Measures in Severely
Immunosuppressed MM Patients
1. Maintain good personal hygiene
1. Handwashing
2. Good dental hygiene
3. Protected sexual encounters
2. Avoid at risk environmental exposure
1. Infected individuals (suspected or confirmed infection)
2. Outdoor activities that pose risk for infections
3. Public swimming pools
3. Take special precautions
1. Food/water
2. Pets
3.Travel
Food & water
Bloodborne & STD
TRAVEL
PRECAUTIONS
Vectors
Animals
Infection Prophylaxis including Vaccination
Conclusions
1. Vaccination:
1. Which ones? S. pneumonia, Influenza and HBV
2. When? individualize but ASAP
3.Vaccinate close contacts
4.Travel vaccines as appropriate
2. Ig replacement
1.Selected patients
2. Individualize dose-schedules/ duration of therapy
3. IV or SC routes
3. Prophylaxis
1. Assess risk for infection
2. Antimicrobial regimens
4. Other preventive measures (including for travel)
THANK YOU
Therapies for Multiple Myeloma and their
Impact on the Immune System
No treatment
Encapsulated bacteria
Ig
M + P
Neutropenia +
Gram-negative
Staphylococcus
VAD
Ig
Encapsulated bacteria
Dexa
Neutropenia ++
Gram-negative
Poli-Cht
T-cell imunity
Staphylococcus
Mucosal candidiasis
BMT, auto/allo
Ig
Encapsulated bacteria
Sequential
Neutropenia ++++
Gram-negative
therapy
Mucositis
Staphylococcus
T-cell immunity
Fungal infections
Viral infections
Post Exposure Prophylaxis for Varicella/Zoster
Determine the risk following exposure:
Pt susceptible? (bortezomib, no vaccination & no H/O varicella)
All immunocompromised pts with H/O varicella can be
considered immune, except HSCT recipients.
Exposure significant enough to result in infection ?
(prolonged face-to-face or close indoor contact 1 h)
Higher risk for complications (severe immunosuppression)?
Post-exposure prophylaxis:
Acyclovir
VariZIG IM within 96 h or 1 dose of IVIG (400 mg/kg)
Varicella vaccine 5 mos after VZIG if safe
The Spectrum of Immunosuppression
Vaccinate
Do not vaccinate* or
poor response
MINIMAL IMMUNOSUPPRESSION
SEVERE
?Thalidomide, lenalidomide, bortezomib?
* Live vaccines
§ 1mg/Kg/day prednisone, 14 days
WHICH
1. Streptococcus pneumoniae
VACCINES?
Risk factors for invasive disease
Defects in humoral immunity
S. pneumoniae
Immunosuppressive therapies
Renal failure / nephrotic syndrome
Asplenia, DM, COPD, CHF
Influenza
Hepatitis B
2. Influenza viruses
3. Hepatitis B viruses
4. Epidemiologic prevalence
1. Remission status
Determinants of 2. Immunosuppressive therapies
response?
particularly HD steroids and
myeloablative chemotherapy
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