Feature

Shingrix, Zostavax show promise against herpes zoster in patients with cancer

Kathleen M. Mullane, DO, PharmD, FIDSA, FAST 
Kathleen M. Mullane
Alemnew F. Dagnew, MD, MSc 
Alemnew F. Dagnew

Both herpes zoster vaccines approved for use in the United States showed promise in preventing the disease in immunocompromised patients with malignancies, according to findings from two phase 3 trials published in The Lancet Infectious Diseases.

One trial showed that the adjuvanted recombinant zoster vaccine (Shingrix, GlaxoSmithKline; RZV) was likely to be beneficial in immunocompromised adult patients with hematological malignancies. The other demonstrated that the inactivated varicella zoster virus vaccine (Zostavax, Merck; VZV) benefitted patients with solid tumor malignancies receiving chemotherapy, but not patients with hematological malignancies.

“Advanced malignancy and associated immunosuppressive therapies are risk factors for herpes zoster,” Kathleen M. Mullane, DO, PharmD, professor of medicine at the University of Chicago, and colleagues wrote in the second study. “The incidence of herpes zoster is approximately 15 cases per 1,000 person-years in patients with solid tumor malignancies receiving chemotherapy and 31 cases per 1,000 person-years in patients with hematological malignancies, compared with nine cases per 1,000 person-years in the general adult population aged 50 years and older (five cases per 1,000 person years across all ages).”

They noted that patients who are immunocompromised are at an increased risk for developing life-threatening complications of herpes zoster, including postherpetic neuralgia, the most common complication from shingles, according to the CDC.

RZV 80% protective

In the U.S., the CDC recommends that healthy adults aged 50 years or older receive two doses of RZV separated by 2 to 6 months.

Alemnew F. Dagnew, MD, MSc, a senior clinical researcher and development lead at GSK, and colleagues conducted a randomized, observer-blind, placebo-controlled trial at 77 centers worldwide to evaluate the safety and immunogenicity of RZV in adults aged 18 years or older with hematological malignancies receiving immunosuppressive cancer treatments.

They randomly assigned participants with hematological malignancies 1:1 to receive two doses of RZV (n = 286) or placebo (n = 283) 1 to 2 months apart during or after immunosuppressive cancer treatments and stratified patients according to their underlying diseases.

According to the researchers, at 2 months, 80.4% (95% CI, 73.1-86.5) of 148 patients had a humoral vaccine response to RZV, compared with 0.8% of 130 patients in the placebo group. Incidences of unsolicited or serious adverse events, fatal serious adverse events, disease-related events and potential immune-mediated diseases were similar between the groups, the researchers reported.

“Despite the immunosuppression, the adjuvanted recombinant zoster vaccine elicited robust and persistent immune responses and showed an acceptable safety profile,” Dagnew told Infectious Disease News. “The results of this study support the use of Shingrix in immunocompromised adult populations, including those with hematologic malignancies.”

In a related editorial, Per Ljungman, MD, PhD, a professor of cellular therapy and allogeneic stem cell transplantation at Karolinska University Hospital in Stockholm, Sweden, wrote that the results support a protective effect of RZV in this vulnerable population.

“It is important to understand that many patients with hematological malignancies are in an age group with an increased risk for herpes zoster, and this risk is further increased by the presence of malignancy,” Ljungman wrote. “Therefore, a safe and effective zoster vaccine would be a valuable addition to the supportive care of these patients.”

VZV efficacious for some patients

According to the CDC, RZV is preferred over the VZV vaccine, which is recommended for adults aged 60 years or older and has been in use since 2006. The VZV vaccine may still be useful in adults who are allergic to RZV or who prefer the VZV vaccine, or in cases of RZV shortage, the CDC noted.

To investigate the efficacy and safety of the inactivated VZV vaccine for herpes zoster prevention in patients with solid tumor or hematological malignancies, Mullane and colleagues conducted a two-arm, randomized, double-blind, placebo-controlled multicenter trial with an adaptive design in 329 centers in 40 countries. They included adult patients with solid tumor malignancies receiving chemotherapy and patients with hematological malignancies either receiving or not receiving chemotherapy. They randomly assigned patients 1:1 to receive four doses of VZV vaccine inactivated by gamma irradiation (n = 2,637) or placebo (n = 2,649).

The researchers terminated the hematological malignancy arm early “because of evidence of futility at a planned interim analysis,” they wrote.

In patients with solid tumor malignancies, the estimated vaccine efficacy was 63.6% (97.5% CI, 36.4-79.1), which met the prespecified success criterion, Mullane and colleagues noted. In these patients, serious adverse events were similar in frequency across treatment groups and occurred in 22.5% of 1,322 patients who received the vaccine and in 21% of 1,346 patients who received placebo (risk difference, 1.5%; 95% CI, –1.7 to 4.6), they said.

According to the researchers, vaccine-related adverse events were less than 1% in each treatment group, but vaccine-related injection-site reactions were more common in the vaccine group than the placebo group.

The VZV vaccine was well tolerated in the hematological malignancy group, but the estimated vaccine efficacy was just 16.8% (95% CI, –17.8 to 41.3).

In a related editorial, Charlotte Warren-Gash, FRCP, PhD, associate professor of epidemiology at the London School of Hygiene & Tropical Medicine, and Judith Breuer, MD, MRCPath, FRCPath, professor of virology and co-director of the division of infection and immunity at the University College London, provided an overview of the study’s implications for the near future.

“Non-live vaccines offer new hope for preventing herpes zoster and its costly complications in individuals who are immunocompromised,” they wrote. “Although implementation plans have yet to be finalized, some countries such as the U.K. are likely to recommend the recombinant herpes zoster vaccine for patients who are immunocompromised and aged 50 years or older in the coming months.” by Joe Gramigna

References:

Dagnew AF, et al. Lancet Infect Dis. 2019;doi:10.1016/S1473-3099(19)30163-X.

Ljungman P, et al. Lancet Infect Dis. 2019;doi:10.1016/S1473-3099(19)30400-1.

Mullane MM, et al. Lancet Infect Dis. 2019:doi:10.1016/S1473-3099(19)30310-X.

Warren-Gash C, et al. Lancet Infect Dis. 2019;doi:10.1016/S1473-3099(19)30399-8.

Disclosures: Breuer reports no relevant financial disclosures. Dagnew is employed by and holds stock options in GSK. Ljungman reports grants from Merck and Shire, as well as personal fees from AiCuris. Mullane reports grants and personal fees from Merck, Astellas Pharma, Chimerix, Scynexis and GSK, as well as grants from Shire and SAGE Therapeutics. Warren-Gash reports no relevant financial disclosures. Please see the studies for all other authors’ relevant financial disclosures.

Kathleen M. Mullane, DO, PharmD, FIDSA, FAST 
Kathleen M. Mullane
Alemnew F. Dagnew, MD, MSc 
Alemnew F. Dagnew

Both herpes zoster vaccines approved for use in the United States showed promise in preventing the disease in immunocompromised patients with malignancies, according to findings from two phase 3 trials published in The Lancet Infectious Diseases.

One trial showed that the adjuvanted recombinant zoster vaccine (Shingrix, GlaxoSmithKline; RZV) was likely to be beneficial in immunocompromised adult patients with hematological malignancies. The other demonstrated that the inactivated varicella zoster virus vaccine (Zostavax, Merck; VZV) benefitted patients with solid tumor malignancies receiving chemotherapy, but not patients with hematological malignancies.

“Advanced malignancy and associated immunosuppressive therapies are risk factors for herpes zoster,” Kathleen M. Mullane, DO, PharmD, professor of medicine at the University of Chicago, and colleagues wrote in the second study. “The incidence of herpes zoster is approximately 15 cases per 1,000 person-years in patients with solid tumor malignancies receiving chemotherapy and 31 cases per 1,000 person-years in patients with hematological malignancies, compared with nine cases per 1,000 person-years in the general adult population aged 50 years and older (five cases per 1,000 person years across all ages).”

They noted that patients who are immunocompromised are at an increased risk for developing life-threatening complications of herpes zoster, including postherpetic neuralgia, the most common complication from shingles, according to the CDC.

RZV 80% protective

In the U.S., the CDC recommends that healthy adults aged 50 years or older receive two doses of RZV separated by 2 to 6 months.

Alemnew F. Dagnew, MD, MSc, a senior clinical researcher and development lead at GSK, and colleagues conducted a randomized, observer-blind, placebo-controlled trial at 77 centers worldwide to evaluate the safety and immunogenicity of RZV in adults aged 18 years or older with hematological malignancies receiving immunosuppressive cancer treatments.

They randomly assigned participants with hematological malignancies 1:1 to receive two doses of RZV (n = 286) or placebo (n = 283) 1 to 2 months apart during or after immunosuppressive cancer treatments and stratified patients according to their underlying diseases.

According to the researchers, at 2 months, 80.4% (95% CI, 73.1-86.5) of 148 patients had a humoral vaccine response to RZV, compared with 0.8% of 130 patients in the placebo group. Incidences of unsolicited or serious adverse events, fatal serious adverse events, disease-related events and potential immune-mediated diseases were similar between the groups, the researchers reported.

“Despite the immunosuppression, the adjuvanted recombinant zoster vaccine elicited robust and persistent immune responses and showed an acceptable safety profile,” Dagnew told Infectious Disease News. “The results of this study support the use of Shingrix in immunocompromised adult populations, including those with hematologic malignancies.”

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In a related editorial, Per Ljungman, MD, PhD, a professor of cellular therapy and allogeneic stem cell transplantation at Karolinska University Hospital in Stockholm, Sweden, wrote that the results support a protective effect of RZV in this vulnerable population.

“It is important to understand that many patients with hematological malignancies are in an age group with an increased risk for herpes zoster, and this risk is further increased by the presence of malignancy,” Ljungman wrote. “Therefore, a safe and effective zoster vaccine would be a valuable addition to the supportive care of these patients.”

VZV efficacious for some patients

According to the CDC, RZV is preferred over the VZV vaccine, which is recommended for adults aged 60 years or older and has been in use since 2006. The VZV vaccine may still be useful in adults who are allergic to RZV or who prefer the VZV vaccine, or in cases of RZV shortage, the CDC noted.

To investigate the efficacy and safety of the inactivated VZV vaccine for herpes zoster prevention in patients with solid tumor or hematological malignancies, Mullane and colleagues conducted a two-arm, randomized, double-blind, placebo-controlled multicenter trial with an adaptive design in 329 centers in 40 countries. They included adult patients with solid tumor malignancies receiving chemotherapy and patients with hematological malignancies either receiving or not receiving chemotherapy. They randomly assigned patients 1:1 to receive four doses of VZV vaccine inactivated by gamma irradiation (n = 2,637) or placebo (n = 2,649).

The researchers terminated the hematological malignancy arm early “because of evidence of futility at a planned interim analysis,” they wrote.

In patients with solid tumor malignancies, the estimated vaccine efficacy was 63.6% (97.5% CI, 36.4-79.1), which met the prespecified success criterion, Mullane and colleagues noted. In these patients, serious adverse events were similar in frequency across treatment groups and occurred in 22.5% of 1,322 patients who received the vaccine and in 21% of 1,346 patients who received placebo (risk difference, 1.5%; 95% CI, –1.7 to 4.6), they said.

According to the researchers, vaccine-related adverse events were less than 1% in each treatment group, but vaccine-related injection-site reactions were more common in the vaccine group than the placebo group.

The VZV vaccine was well tolerated in the hematological malignancy group, but the estimated vaccine efficacy was just 16.8% (95% CI, –17.8 to 41.3).

In a related editorial, Charlotte Warren-Gash, FRCP, PhD, associate professor of epidemiology at the London School of Hygiene & Tropical Medicine, and Judith Breuer, MD, MRCPath, FRCPath, professor of virology and co-director of the division of infection and immunity at the University College London, provided an overview of the study’s implications for the near future.

“Non-live vaccines offer new hope for preventing herpes zoster and its costly complications in individuals who are immunocompromised,” they wrote. “Although implementation plans have yet to be finalized, some countries such as the U.K. are likely to recommend the recombinant herpes zoster vaccine for patients who are immunocompromised and aged 50 years or older in the coming months.” by Joe Gramigna

References:

Dagnew AF, et al. Lancet Infect Dis. 2019;doi:10.1016/S1473-3099(19)30163-X.

Ljungman P, et al. Lancet Infect Dis. 2019;doi:10.1016/S1473-3099(19)30400-1.

Mullane MM, et al. Lancet Infect Dis. 2019:doi:10.1016/S1473-3099(19)30310-X.

Warren-Gash C, et al. Lancet Infect Dis. 2019;doi:10.1016/S1473-3099(19)30399-8.

Disclosures: Breuer reports no relevant financial disclosures. Dagnew is employed by and holds stock options in GSK. Ljungman reports grants from Merck and Shire, as well as personal fees from AiCuris. Mullane reports grants and personal fees from Merck, Astellas Pharma, Chimerix, Scynexis and GSK, as well as grants from Shire and SAGE Therapeutics. Warren-Gash reports no relevant financial disclosures. Please see the studies for all other authors’ relevant financial disclosures.