Vaccination in Immunosuppressed Adults

ASID Adult Immunisation Workshop 9 May 2018

Professor Katie Flanagan

Types of Immunosuppression to Consider

• Cancer and haematological malignancies • Chronic infections – HIV • Chronic diseases – diabetes, COPD, autoimmune diseases • Asplenia • Physiological – pregnancy • Stem Cell / Solid organ / bone marrow transplant • Drug induced

– Steroids – Other immunosuppressive drugs – methotrexate, azathioprine – Cancer and haematological malignancy treatments

• Immunotherapies – Monoclonal antibodies – Immune checkpoint inhibitors

General Rules • Immune compromised persons are at increased risk of morbidity and

mortality from many VPDs. • Degree of immune compromise should be assessed to determine vaccination

strategy

• Inactivated vaccines are generally safe in the immunocompromised adult but not always as immunogenic / efficacious

• Live vaccines are contraindicated in many immunocompromising situations due to risk of disseminated infection, in particular: – BCG is always contraindicated – Other live vaccines should not be given to those with severe immunocompromise

• Severe immunocompromise includes active leukaemia, lymphoma,

generalised malignancy, recent chemo (last 3 months), aplastic anaemia, GVHD, BMT or solid organ transplant in last 2 years, transplant recipients still taking immunosuppressives, high-dose corticosteroids

General Rules

• Many vaccines can be given pre-emptively to people who anticipate immunocompromise in the future i.e. contemplating immunosuppressive therapy e.g. varicella zoster vaccine, pneumococcal vaccination

Influenza Vaccination

• Annual seasonal vaccination recommended for all immune compromised adults

• Should be given 2 doses at least 4 weeks apart the first time it is given

• In a pandemic situation 2 doses of vaccine may be given any season

Cancer / Haematology Patients

Live vaccines

• Contraindicated if on immunosuppressive therapy or have poorly

controlled malignancy

• Avoid when neutropaenic (<0.5x109/L)

• Wait until 3 months after treatment and confirmed remission

Inactivated Vaccines

• Give annual influenza (2 doses 1st time)

• Give any required inactivated vaccines

• Haematological malignancy patients (lymphoma, leukaemia, myeloma)

should be given pneumococcal vaccination – 1 dose of 13 valent PCV then

2 doses of 23 valent PPV 8 weeks after PCV

Adult Cancer / Haematology Patients in Remission for >6 months

• Single dose dTpa

• Single dose MMR / IPV / HepB

(Check measles and rubella Abs 6-8 weeks after MMR and revaccinate if

non- seroconverter)

• Single dose 13vPCV then 2 doses 23vPPV

• Single dose Hib

Solid Organ Transplant

Live vaccines contraindicated

Inactivated vaccines safe but often delayed until 6 months post-Tx to maximise immunogenicity

Vaccine Pre-Transplant Post-Transplant

(if not given before)

dTpa Yes Yes

IPV Yes Yes

Hep A and B Yes (depends on serostatus) Yes (depends on serostatus)

13vPCV then 2 x 23vPPV

Yes Yes

MenACWY and MenB

Yes (if risk factors) Yes (if risk factors)

Annual influenza Yes

MMR Yes No

Haematopoietic Stem Cell Transplant

Protective immunity to VPDs partially or fully lost post HSCT, particularly first 6 months

Autologous HSCT patients recover immunity more quickly & don’t get GVHD Vaccine Schedule

13vPCV 3 doses 6, 8, 12m post HSCT

23vPPV 1 dose 24m post HSCT

Hib / dTpa / IPV 3 doses 6, 8, 12m post HSCT

HepB 3 doses 6, 8, 12m post HSCT High dose formulation or dose in each arm each visit

4vMenCV and MenB 2 doses 6 and 8m

MMR * 24m - 1-2 doses (check Abs at 4wks)

Varicella * 24m - 2 doses 4wks apart if seronegative

* Only if no ongoing GVHD and CMI has recovered There is a role for donor immunisation with Hib, PCV, hep B and tetanus vaccines prior to harvest but rarely done

Corticosteroids and Live Vaccines

Prednisolone Equivalent Dose

Duration Timing of Vaccination

<20mg / day Any Give any time

≥20mg / day < 14 days 1 month before or any time after

cessation

≥20mg / day

≥14 days 1 month before or at least 1 month after cessation

20mg prednisolone is equivalent to: 16 mg methylprednisolone 16mg triamcinolone 3.2mg dexamethasone 80mg hydrocortisone

Corticosteroids and DMARDS

• If on <20mg prednisolone equivalent daily and low dose DMARDS then can still receive live vaccines

• Low dose DMARDS:

Drug Dose Dose in 70kg adult

Methotrexate ≤0.4mg/kg/week 28mg

Azathioprine ≤3mg/kg/day 210mg

Mercaptopurine ≤1.5mg/kg/day 105mg

Recent Blood Products / Immunoglobulins

Product Interval Before Live (MMR, MMRV, Varicella) Vaccination

Blood transfusion / washed RBCs 0 months

RBCs 3 months

Packed RBCs 5 months

Whole blood 6 months

NHIG for ITP / Kawasaki NHIG for measles / hepA prophylaxis

8-11 months 3-6 months

Plasma or platelets 7 months

RhD Ig (anti-D) 0 months

ZIG as varicella prophylaxis 5 months

BCG, Zoster and Yellow Fever vaccination can be given any time before or after blood products

HIV Infection Live vaccines • Contraindicated if CD4 <200/μL (<15%), history of AIDS-defining illness,

symptomatic HIV infection • BCG is always contraindicated • Can give YF, MMR (if seronegative) and VZV (if seronegative) vaccines but NOT

combined MMRV in asymptomatic HIV infection and those with CD4 ≥200/μL (15%)

• Zoster vaccine if ≥ 50 years and VZV IgG+ and CD4 ≥350/μL (some say ≥200/μL safe)

Inactivated Vaccines • Annual influenza • Pneumococcal vaccination (1 x PCV13 + 2x PPV23) • 4vMenCV and MenB – 2 doses of each • HepA if non-immune • HepB 4 double doses at 0, 1, 2 and 6m more immunogenic, check anti-HBs and

repeat doses if <10mIU/mL • 4vHPV – 3 doses @ 0, 2 and 6m. Females <45 yrs and males <26 yrs as per

guidelines

Asplenia At risk of fulminant bacterial infection particularly invasive pneumococcal disease Go to Spleen Australia website for up-to-date advice https://spleen.org.au

Immunocompromised Travellers

• Yellow fever vaccine should be avoided in severe immunocompromise (travellers may need an exemption certificate)

• Do not give BCG

• Use the inactivated typhoid Vi polysaccharide vaccine not the live oral vaccine

Household Contacts

• Vaccinate household and close contacts of immunocompromised persons

according to current recommendations

– In particular annual influenza vaccination

• Use of live vaccines in contacts is highly recommended

• Consider need for VZV (if ≥50 years) and pertussis-containing vaccines

• Small risk of rotavirus vaccine virus transmission to the

immunocompromised

Name Target

Bimagrumab Type II activin recptors

Alirocumab PCSK-9

Bocociziumab PCSK9

MABp1, Xilonix IL-1α

Gevokizumab IL-1β

Dupilumab IL-4Rα

Reslizumab IL-5

Benralizumab IL-5R

Sirukumab IL-6

Sarilumab /SA237 IL-6R subunit α

Lebrikizumab / Tralokinumab IL-13

Ixekizumab IL-17a

Brodalumab IL-17R

Tildrakizumab / Guselkumab IL-23 p19 subunit

Name Target

Actoxumab + Bezlotoxumab C diff enterotoxin A & B

Etrolizumab β7 integrin subunit

Tremelimumab CTLA4

MM-302 HER2

Patritumab HER3

MEDI-4736 / RG7446, MPDL3280A

PD-L1

Elotuzumab CD2

Inotuzumab ozogamicin / Moxetumomeb pasudotoc

CD22

Daratumumab CD38

Eculizumab Anti-complement C5

Rituximab / Ocrelizumab CD20

Alemtuzumab CD52

Epratuzumab CD22

Immunotherapies

Rituximab

• Depletes B cells (anti-CD20) therefore prevents antibody responses

• Different studies show differing effects but generally vaccine Ab responses (and CMI) impaired for up to 6 months post administration

• Preferable to vaccinate prior to commencing therapy if possible

• Prevents formation of the terminal complement complex C5b-9, by inhibiting the cleavage of C5-C5a

• Indications: paroxysmal nocturnal haemoglobinuria and atypical haemolytic uraemic syndrome

• Worlds most expensive drug, 2010 (£340,000/dose)

• Associated with increased susceptibility to serious Neisseria meningitidis infection with a rate of 1% (Australian average rate: 1/100,000)

• Meningococcal vaccination recommended before starting treatment 4vMenV and MenBV 2 doses 8 weeks apart then check titres for response

• Check Ab titres annually if ongoing therapy and revaccinate if titres fall

• Antibiotic prophylaxis (PenV / erythromycn) also indicated

Eculizumab

Immune Checkpoint Inhibitors & Flu Vaccination

• Influenza vaccination has been associated with increased incidents of myocarditis and death in people on checkpoint inhibitors

• One study showed PD-1/PD-L1 inhibs caused >50% immune related AEs (rash, arthritis, encephalitis, colitis) (>25% had severe irAEs)

• Australian immunisation handbook says to consult your oncologist for advice

• They are likely to ask the ID physician!

• Trials are ongoing to investigate this systematically

• Pembrolizumab (PD-1 inhibitor), Nivolumab (PD-1 inhibitor), Atezolizumab (PD-L1 inhibitor), Ipilimumab (CTLA4 inhibitor)

Can give if on single agent aPD-1 or aPD-L1 Do not give flu vaccine within 6-8 wks of starting CTLA4 inhibs / combo therapy or 6-8 wks of stopping

Thank You