Solid, Hematological Malignancies Show Different Responses to Zoster Vaccines

By Will Boggs MD

August 19, 2019

NEW YORK (Reuters Health) - Inactivated varicella zoster virus (VZV) vaccine elicits protective responses in immunosuppressed patients with solid tumor malignancies, whereas patients with hematological malignancies respond to adjuvanted recombinant zoster vaccine, according to a pair of new studies.

"Immunocompromised individuals may respond to vaccines, and it is reasonable to vaccinate patients who are on chemotherapy in order to help protect them from infections for which there are vaccines that are active," Dr. Kathleen M. Mullane of the University of Chicago told Reuters Health by email.

Patients with malignancies have an incidence of herpes zoster two to three times that in the general adult population aged 50 years and older, and live attenuated vaccine is contraindicated in immunosuppressed patients, Dr. Mullane and colleagues in the V212 Protocol 011 trial team note in The Lancet Infectious Diseases, online August 6. Possible alternatives include an inactivated VZV vaccine and a recombinant subunit VZV vaccine.

The researchers assessed the efficacy and safety of a VZV vaccine inactivated by gamma irradiation for the prevention of herpes zoster and related complications in 2,712 patients with solid tumors receiving chemotherapy and 2,573 patients with hematological malignancies.

Among patients with solid tumor malignancies, there were 22 confirmed herpes zoster cases (6.7 per 1.000 person-years) in the vaccine group versus 61 confirmed cases (18.5 per 1,000 person-years) in the placebo group, for an estimated vaccine efficacy of 63.6%.

Estimated vaccine efficacy against herpes zoster declined from 80.7% after up to six months from randomization to 79.7% after six to 12 months and 43.8% beyond 12 months.

In contrast, the inactivated VZV vaccine did not reduce herpes zoster incidence compared with placebo in patients with hematological malignancies.

"Unfortunately Merck is not going to market the vaccine," Dr. Mullane said. "Because inactivated Zostavax will not be marketed, the only non-live vaccine is Shingrix (the recombinant vaccine). There is no data on efficacy in this population; therefore, the decision on whether or not to use it would be up to the patient's primary provider."

Shingrix was the subject of the second study, published along with the first. Dr. Alemnew F. Dagnew from GlaxoSmithKline, in Rockville, Maryland, and colleagues in the Zoster-039 study group evaluated its safety and immunogenicity in 606 adults with hematological malignancies who had been receiving immunosuppressive cancer treatments.

At month 2, 65.4% of the vaccine group and 0.5% of the placebo group had a humoral vaccine response. Anti-glycoprotein E antibody geometric mean concentrations increased from 964.0 mIU/mL at baseline to 13,445.6 mIU/mL at two months in the vaccine group, but did not change significantly in the placebo group.

At month 13, 52.1% of the vaccine group and 3.6% of the placebo group had a humoral vaccine response. At that point, mean anti-glycoprotein E antibody concentrations had fallen to 5,202.7 mIU/mL in the vaccine group.

During follow-up, two participants in the vaccine and 12 participants in the placebo group had confirmed herpes zoster episodes.

In both studies, the incidence of serious adverse events was similar between the vaccine and placebo groups.

GSK spokesman Sean Clements told Reuters Health by email, "A third of participants were vaccinated during immunosuppressive therapy and two-thirds were vaccinated after finishing immunosuppressive therapy. Despite the immunosuppression, the adjuvanted recombinant zoster vaccine elicited robust and persistent humoral and cell-mediated immune responses and showed an acceptable safety profile. Data from a post-hoc analysis of confirmed herpes zoster cases supports that the vaccine is efficacious in preventing herpes zoster."

"While currently not indicated for immunocompromised individuals, GSK believes that Shingrix, as a recombinant, protein-based vaccine, could potentially provide benefit for the prevention of herpes zoster in these immunocompromised populations, helping protect against shingles in a population experiencing especially high incidence and burden of disease," he said.

"GSK's clinical development program evaluated Shingrix in immunocompromised populations, including trials in individuals with solid tumors, hematological malignancies, as well as individuals who have a history of hematopoietic stem cell transplant (HSCT), and renal transplant recipients," Clements said. "Data generated from these trials are being shared and discussed with regulatory and public health agencies with the objective of best informing health care providers on the use of Shingrix in immunocompromised individuals."

He added, "Immunocompromised patients were excluded from the pivotal clinical trials for Shingrix, and consequently is not in our label. In this study, adults aged 18 years and older with various hematologic malignancies were evaluated, and it is to be noted that the vaccine has not yet been licensed for use in adults aged 18 to 49 years."

"Non-live vaccines offer new hope for preventing herpes zoster and its costly complications in individuals who are immunocompromised," write Dr. Charlotte Warren-Gash of London School of Hygiene and Tropical Medicine and Dr. Judith Breuer of University College London in an accompanying editorial. "Although implementation plans have yet to be finalized, some countries such as the UK are likely to recommend the recombinant herpes zoster vaccine for patients who are immunocompromised and aged 50 years or older in the coming months."

"Large studies with clinically meaningful endpoints will provide further insights into the relative efficacies, duration of protection, long-term safety, and cost-effectiveness of non-live zoster vaccines for different immunocompromised groups," they conclude.

"It seems logical that elderly patients with hematological malignancies, who have an indication for herpes zoster vaccination on the basis of age, could safely receive the adjuvanted recombinant vaccine," writes Dr. Per Ljungman from Karolinska Institutet, in Stockholm, in an editorial about the second report. "However, it is unclear if additional doses will be needed to maintain an immune response."

"Additional studies are needed to address the relative roles of this vaccine and antiviral prophylaxis and when best to apply different preventive strategies against varicella zoster reactivation in immunocompromised patients with hematological malignancies," he said.

Merck and Company, Inc. funded the V212 Protocol 011 study and employed several authors and has financial ties to Dr. Mullane and Dr. Ljungman.

GlaxoSmithKline Biologicals SA funded the Zoster-039 study and also employed several authors.

SOURCE: https://bit.ly/2MXq676, https://bit.ly/2KNiFwx, https://bit.ly/307mGT1 and https://bit.ly/2YPX4x6

Lancet Infect Dis 2019.

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