Treatment with an inactivated varicella zoster virus vaccine, known as V212, lowered the cumulative incidence rate of herpes zoster (HZ) infection and HZ-related complications for patients undergoing autologous stem cell transplantation (ASCT), according to findings from a phase III study presented at the 2017 BMT Tandem Meetings.
After 2.3 years of follow-up, confirmed cases of HZ by PCR were seen in 42 of 538 patients (7.8%) treated with the vaccine versus 113 of 535 patients (21.1%) who received a placebo (P
<.0001). Once adjusting for age and antiviral prophylaxis, the vaccine was estimated to be 63.8% effective against HZ (95% CI, 48.4-74.6).
"The study demonstrates that the inactivated varicella vaccine is very effective for prevention of herpes zoster after autologous transplant," summarized Drew J. Winston, MD, from the University of California Los Angeles Medical Center, during his talk at the meeting. "The vaccine also reduces the incidence of moderate-to-severe pain, post-herpetic neuralgia, and herpes zoster complications after autologous transplantation."
In the trial, patients received V212 (n = 560) and a matching placebo (n = 564) at 0.5 mL subcutaneously approximately 30 days prior to ASCT (range, 5-60), followed by 3 subsequent injections on days 30, 60, and 90 post-transplant. An additional arm looked at a high antigen version of the vaccine (n = 106). The high antigen arm was not included in the efficacy analysis but was part of the safety assessment.
Patient characteristics were well-balanced between the groups. In the investigational arm, the most common underlying diseases were non-Hodgkin's lymphoma (42%), multiple myeloma (44%), and Hodgkin's lymphoma (10%). Ninety percent of patients received conditioning chemotherapy.
Post-transplant maintenance therapy was received by a third of patients, most commonly lenalidomide (15%), bortezomib (11%), and rituximab (7%). Post-treatment antiviral therapy was utilized for ≤3 months for a third of patients, with 20% receiving these therapies for 3 to 6 months and 37% for >6 months. Twelve percent of patients did not receive antiviral therapy.
The primary endpoint was the incidence of HZ, which was deemed statistically improved if the lower end of the confidence interval was greater than 25%. Secondary endpoints focused on severity of HZ-associated pain, HZ complications, and the incidence of post-herpetic neuralgia (PHN). Only those who went on to receive ASCT and the vaccine were include in the efficacy analysis.
Moderate-to-severe HZ-related pain was experienced by 3.5% of those in the vaccine arm versus 11.4% in the placebo group, showing the vaccine was 69.5% effective for this endpoint (95% CI, 0.490-0.818). PHN occurred in just 0.5% of those in the vaccine arm versus 3.4% in the placebo group (83.7% efficacy; 95% CI, 0.446-0.952). HZ complications occurred in 2.2% versus 8.2% of those in the vaccine and placebo arms, respectively (73.5% efficacy; 95% CI, 0.498-0.860).
In those aged <50 years, in the vaccine arm (n = 154) the HZ incidence was 4.5% compared with 17.9% in the placebo arm (n = 151). In those ≥50 years of age, in the vaccine group (n = 384) the HZ rate was 9.1% versus 22.4% in the placebo arm (n = 384).
In those who received antivirals for ≤3 months, in the vaccine arm (n = 228) 9.7% had an HZ infection versus 21.3% in the placebo group (n = 239). In those treated with antivirals for 3 to 6 months, the HZ rate was 7.1% in the vaccine group (n = 310) versus 20.9% in the placebo group (n = 296).
Vaccine-related adverse events (AEs) occurred in 32.6% of patients in the investigational arm versus 12.6% in the placebo group, many of these events were associated with the high antigen vaccine. Most of the events reported were injection site reactions (29.1% vs 6.5%). The rates of serious AEs were similar between the vaccine and placebo arms, at 32.9% and 32.7%, respectively. Serious vaccine-related AEs were 0.8% and 0.9%, in the V212 and placebo arms, respectively.
“These results indicate that V212 might offer a way to help reduce the risk of HZ and HZ-related complications in this vulnerable, immunocompromised patient population,” Eliav Barr, MD, senior vice president, Merck Research Laboratories, the company developing the vaccine, said in a statement. “We look forward to exploring these data further and to reviewing the results of an additional phase III study that is underway in immunocompromised patients with malignancies.”
A larger phase III study is examining the efficacy, safety, and tolerability of V212 for patients with solid tumors or hematologic malignancy. The trial is comparing the vaccine with placebo across 5307 patients, with primary endpoints of reduction in HZ cases and safety. The study is fully enrolled with an estimated completion date in April 2017 (NCT01254630).
Winston DJ, Mullane KM, Boeckh MJ, et al. A Phase III, Double-Blind, Randomized, Placebo-Controlled, Multicenter Clinical Trial to Study the Safety, Tolerability, Efficacy, and Immunogenicity of Inactivated Vzv Vaccine (ZVIN) in Recipients of Autologous Hematopoietic Cell Transplants (Auto-HCTs). Presented at: BMT Tandem Meetings; February 22-26, 2017; Orlando, FL. Abstract 6.
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