The Hematologist

July-August 2018, Volume 15, Issue 4

New Herpes Zoster Vaccine: What the Hematologist Needs to Know

Luis Malpica Castillo, MD Hematology/Oncology Fellow
University of North Carolina, Chapel Hill, NC
Stephan Moll, MD Professor of Medicine, Division of Hematology/Oncology
University of North Carolina School of Medicine, Chapel Hill, NC

Published on: July 02, 2018

Dooling KL, Guo A, Patel M, et al. Recommendations of the Advisory Committee on Immunization Practices for use of herpes zoster vaccines. MMWR Morb Mortal Wkly Rep. 2018;67:103-108.

The lifetime risk of developing herpes zoster (HZ), the clinical manifestation of varicella zoster virus (VZV) reactivation, is estimated to be 20 to 30 percent, with an incidence in the United States of about one million cases each year.1 The risk typically increases with age (especially older than age 50 years) and when cell-mediated immunity is diminished, as occurs with use of immunosuppressive drugs.1-3 Zoster vaccine live (Zostavax; Merck & Co., Inc., Whitehouse Station, NJ), a vaccine containing a strain of live attenuated VZV, was approved by the U.S. Food and Drug Administration (FDA) in 2006 after it was shown to reduce the incidence of HZ by 51.3 percent in a study of 38,000 adults aged 60 years and older. The vaccine also reduced the number of cases of postherpetic neuralgia (PHN), and the severity/duration of pain associated with HZ by 66.5 percent and 61.1 percent, respectively.1 In the United States, recommendations for the use of vaccines are created by the Advisory Committee on Immunization Practices (ACIP), a committee of medical and public health experts reporting to the director of the Centers for Disease Control and Prevention (CDC), that are then accepted and promoted by the CDC. In 2006, CDC/ACIP recommended that zoster vaccine live be given to all adults aged 60 years and older, including those with a previous episode of HZ and those not recalling having had chickenpox. In 2011, the FDA approved the vaccine’s use in individuals 50 to 59 years of age.1 On October 20, 2017, a recombinant zoster vaccine, zoster vaccine recombinant (Shingrix; GlaxoSmithKline Biologicals, Rixensart, Belgium), was approved by the FDA for the prevention of HZ in adults aged 50 years and older based on a phase III clinical study that showed a sustained efficacy of more than 90 percent against HZ across all age groups during a four-year follow-up period (HZ prevention: efficacy of 96.6% in ages 50-59 years, 97.4% in ages 60-69 years, and 91.3% in ages ≥70 years; PHN: efficacy of 91.2% in ages ≥50 years and 88.8% in ages ≥70 years).4

  • Given how prevalent HZ is and how frequently immunosuppressive therapy is prescribed for the treatment of hematologic disorders, the present CDC/ACIP publication by Dr. Kathleen Dooling and colleagues is highly relevant for the practicing hematologist. CDC/ACIP recommend that for the prevention of HZ and related complications, zoster vaccine recombinant is preferred over zoster vaccine live. As with zoster vaccine live, the CDC/ACIP recommend the use of zoster vaccine recombinant in all persons older than 50 years, in persons taking low-dose immunosuppressive therapy (e.g., <20 mg/day of prednisone or equivalent, or using inhaled or topical steroids), and in those anticipating immunosuppression or who have recovered from an immunocompromising illness (Table). The ACIP has not made recommendations regarding the use of zoster vaccine recombinant in immunocompromised persons and those on moderate to high doses of immunosuppressive therapy as these patients were excluded from the phase III efficacy studies (ZOE-50 and ZOE-70 trials).4 This patient population will likely be discussed at upcoming ACIP meetings as additional data become available. However, published data have already shown that patients immunized with zoster vaccine recombinant who were 18 years or older, had hematologic malignancies (excluding non-Hodgkin B cell lymphoma or chronic lymphocytic leukemia), and completed or are undergoing immunosuppressive cancer therapy, showed a robust humoral and cellular immune responses to the vaccine at one month after last dose, with no safety concerns at six months follow-up after last dose.5
CDC/ACIP Recommendations for the Use of Herpes Zoster Vaccines
1. All immunocompetent adults aged ≥50 years, including those who:
  • Received zoster vaccine live in the past.a
  • Had chickenpox, or do not recall whether they had chickenpox or not.
  • Have history of herpes zoster (shingles), but not an active flare at the time of vaccination.
  • Have chronic medical conditions (e.g., chronic renal failure, diabetes mellitus, rheumatoid arthritis, chronic pulmonary diseases.)
2. Anticipating immunosuppression or currently mildly to moderately immunosuppressed:
  • Adults aged ≥50 years, who are:
    • Anticipating immunosuppression (vaccinate ideally ≥4 weeks before treatment).
    • Taking low-dose immunosuppressive therapy (e.g., <20 mg/day of prednisone or equivalent, or using inhaled or topical steroids, azathioprine, mycophenolate mofetil).
    • Recovered from an immunocompromising illness.
  • Adults aged <50 years: ACIP does not have a recommendation to administer either zoster vaccine to people younger than 50 years.b
3. Currently severely immunocompromised (e.g. chemotherapy, high-dose/long-term: steroids, azathioprine, mycophenolate mofetil, others): ACIP does not have a recommendation to administer either zoster vaccine in this population.c
4. Other comments:
  • It is not necessary to screen, either verbally or by laboratory serology, for evidence of prior varicella infection. This ACIP guideline applies no matter whether patient is seronegative or seropositive for VZV.
  • Zoster vaccine recombinant is preferred over ZVL (Zostavax®).
  • Zoster vaccine live is preferred if a person is allergic to Shingrix®, or requests immediate vaccination and Shingrix is unavailable.d

a. Studies examined the safety and immunogenicity of RZV vaccination administered ≥5 years after ZVL6; shorter intervals have not been studied. However, there are no data or theoretical concerns to indicate that RZV would be less safe or less effective when administered at an interval of <5 years. Clinical trials indicated lower efficacy of ZVL in adults aged ≥70 years; therefore, a shorter interval may be considered based on the recipient’s age when ZVL was administered. Based on expert opinion, RZV should not be given <2 months after receipt of ZVL.1

b. Clinicians may choose to administer a vaccine off-label, if in their clinical judgment, they think the vaccine is indicated (e.g. history of chickenpox or lack of recall whether patient had chickenpox). The patient should be informed that the use is off-label, and that efficacy and safety of the vaccine have not been tested in people younger than 50. 

c. Even though it is unclear whether immunocompromised individuals on active immunosuppressive therapy will be able to build an immune response after receiving RZV vaccine, preliminary data show that it may be reasonable to consider vaccinating patients on active immunosuppressive therapy (e.g. active chemotherapy)5; however, the study excluded patients with B-cell hematologic malignancies (e.g. non-Hodgkin lymphomas), or on B-cell depleting agents (e.g. Rituximab).

d. Zostavax® can be used in patients aged 60 years and older if there is no contraindication for live attenuated vaccine (e.g. HIV, pregnancy). If high dose corticosteroids (>20 mg/day of prednisone equivalent) are given, vaccination should be deferred for at least one month after discontinuation of such therapy.1

How is our practice influenced by the recent recombinant HZ vaccine study findings, the vaccine’s FDA approval, and the CDC/ACIP recommendations? In patients 50 years and older in whom immunosuppressive therapy is planned, we immunize against HZ at least two to four weeks before planned treatment. This immunization is in addition to influenza virus vaccine, and in certain patient subgroups (those to receive rituximab therapy or to undergo splenectomy) the so-called “triple vaccine” (pneumococcal, meningococcal, and haemophilus influenza vaccines). With any HZ vaccination, zoster vaccine recombinant is now preferred over zoster vaccine live. While zoster vaccine live is given as a single subcutaneous dose, zoster vaccine recombinant is given as two intramuscular doses, two to six months apart. The Table provides a summary of the current CDC/ACIP recommendations, with added comments on our approach in specific patient populations.

References

  1. Dooling KL, Guo A, Patel M, et al. Recommendations of the Advisory Committee on Immunization Practices for use of herpes zoster vaccines. MMWR Morb Mortal Wkly Rep. 2018;67:103-108.
  2. Chakravarty EF. Incidence and prevention of herpes zoster reactivation in patients with autoimmune diseases. Rheum Dis Clin North Am. 2017;43:111-121.
  3. Zorzoli E, Pica F, Masetti G, et al. Herpes zoster in frail elderly patients: prevalence, impact, management, and preventive strategies. Aging Clin Exp Res. 2018; doi: 10.1007/s40520-018-0956-3. [Epub ahead of print].
  4. Cunningham AL, Lal H, Kovac M, et al. Efficacy of the herpes zoster subunit vaccine in adults 70 years of age or older. N Engl J Med. 2016;375:1019-1032.
  5. Oostvogels L. Immunogenicity and safety of an adjuvanted herpes zoster subunit candidate vaccine in adults with hematologic malignancies: a phase III, randomized clinical trial. Open Forum Infect Dis. 2017; doi: 10.1093/ofid/ofx163.1040. [Epub ahead of print].
  6. Grupping K, Campora L, Douha M, et al. Immunogenicity and safety of an adjuvanted herpes zoster subunit vaccine in older adults previously vaccinated with a live-attenuated herpes zoster vaccine: a phase III, group-matched, clinical trial. Open Forum Infect Dis. 2017; doi: 10.1093/ofid/ofx163.1038. [Epub ahead of print].

Conflict of Interests

Dr. Malpica Castillo and Dr. Moll indicated no relevant conflicts of interest. back to top