In the Journals

Triplex vaccine reduces CMV complications in stem cell transplant recipients

Don J. Diamond, PhD
Don J. Diamond

The novel Triplex vaccine induced immunity to cytomegalovirus, or CMV, and reduced rates of complications from the virus in patients undergoing allogeneic hematopoietic stem cell transplant, according to results from a phase 2 randomized clinical trial published in Annals of Internal Medicine.

Results from a phase 1 trial of Triplex that were published in 2017 in Blood previously demonstrated the vaccine’s effectiveness in generating protective CMV-specific immunity in CMV-seropositive hematopoietic stem cell, or HCT, recipients.

“The results of the study suggest that more patients can be protected from the ravages of virus reactivation and multiplication, which can lead to pneumonia, disease of the gastrointestinal tract, and other organ systems being infected to the point where they can be rendered nonfunctional,” Don J. Diamond, PhD, professor in the department of hematology and hematopoietic cell transplantation at the City of Hope National Medical Center and Beckman Research Institute, told Healio. “The positive results of the clinical trial are good news for transplant recipients, patients with HIV and others who might benefit from Triplex vaccination.”

Diamond and colleagues studied 102 CMV-seropositive HCT recipients at high risk for CMV reactivation to determine Triplex’s efficacy in reducing complications from CMV. They randomly assigned patients in a 1:1 ratio to receive either Triplex (n = 51) or a placebo (n = 51) on days 28 and 56 following HCT. All patients received the first vaccine; most patients (89.2%) received both (n = 46 for Triplex and 45 for placebo).

The study’s primary outcomes included CMV events (defined as a CMV DNA level greater than or equal to 1,250 IU/mL, CMV viremia requiring antiviral treatment or end-organ disease), nonrelapse mortality and grade 3 or 4 graft-versus host disease. All outcomes were evaluated through 100 days following HCT.

Reactivation of CMV occurred in five of the patients given Triplex (9.8%) and 10 who received the placebo (19.6%). Despite having transplant-induced weakened immune systems, patients who received Triplex also developed CMV immunity 197% higher than patients who received placebo. None of the patients vaccinated with Triplex died because of nonrelapse causes in the first 100 days or had serious adverse events. No grade 3 or 4 vaccine-related adverse events occurred in the first 2 weeks after vaccination.

Diamond emphasized the benefits of the vaccine on the immune system compared with antiviral medication.

“There is a biologic or immunotherapy that could be available in the near future that would replace antiviral prophylactic medications such as Merck’s letermovir (Prevymis) that is required to be taken once daily for 100 days,” Diamond said. “The vaccine would at most be administered three times to the recipient and possibly one time to their donor. The risk for developing resistance to an antiviral drug is eliminated by switching to the vaccine. In addition, the reconstitution of the immune system that the vaccine promotes is a healthy consequence, because antivirals generally do not allow the reconstitution of the immune system that targets the pathogen they are affecting.”

Diamond also noted that further vaccine research could benefit other subgroups of transplant patients.

“This clinical trial is the first in stem cell transplant for this agent and needs to be followed up with a phase 3 registration trial so the vaccine can be made available to patients with this unmet medical need,” Diamond said. “There are additional patients who we believe will benefit from the Triplex vaccine, which includes the haploidentical transplant recipients that are growing in number annually because of the superior outcomes vs. cord blood transplant and the ease of identifying donors without legal implications that have plagued some cord blood initiatives.”– by Eamon Dreisbach

Reference:

Diamond DJ, et al. Blood. 2015;doi:10.1182/blood.V126.23.3108.3108.

Aldoss I, et al. Ann Intern Med. 2020;doi:10.7326/M19-2511.

Disclosures: Diamond reports grants from Helocyte Inc. and NIH during the conduct of the study. He also reports, grants, personal fees and other support from Helocyte Inc. and nonfinancial support from Pfizer Inc. unrelated to this study. In addition, Diamond reports a patent 8,580,276 with royalties paid to Helocyte and a patent 9,675,689 with royalties paid to Helocyte. Please see the study for the other authors’ relevant financial disclosures.

Don J. Diamond, PhD
Don J. Diamond

The novel Triplex vaccine induced immunity to cytomegalovirus, or CMV, and reduced rates of complications from the virus in patients undergoing allogeneic hematopoietic stem cell transplant, according to results from a phase 2 randomized clinical trial published in Annals of Internal Medicine.

Results from a phase 1 trial of Triplex that were published in 2017 in Blood previously demonstrated the vaccine’s effectiveness in generating protective CMV-specific immunity in CMV-seropositive hematopoietic stem cell, or HCT, recipients.

“The results of the study suggest that more patients can be protected from the ravages of virus reactivation and multiplication, which can lead to pneumonia, disease of the gastrointestinal tract, and other organ systems being infected to the point where they can be rendered nonfunctional,” Don J. Diamond, PhD, professor in the department of hematology and hematopoietic cell transplantation at the City of Hope National Medical Center and Beckman Research Institute, told Healio. “The positive results of the clinical trial are good news for transplant recipients, patients with HIV and others who might benefit from Triplex vaccination.”

Diamond and colleagues studied 102 CMV-seropositive HCT recipients at high risk for CMV reactivation to determine Triplex’s efficacy in reducing complications from CMV. They randomly assigned patients in a 1:1 ratio to receive either Triplex (n = 51) or a placebo (n = 51) on days 28 and 56 following HCT. All patients received the first vaccine; most patients (89.2%) received both (n = 46 for Triplex and 45 for placebo).

The study’s primary outcomes included CMV events (defined as a CMV DNA level greater than or equal to 1,250 IU/mL, CMV viremia requiring antiviral treatment or end-organ disease), nonrelapse mortality and grade 3 or 4 graft-versus host disease. All outcomes were evaluated through 100 days following HCT.

Reactivation of CMV occurred in five of the patients given Triplex (9.8%) and 10 who received the placebo (19.6%). Despite having transplant-induced weakened immune systems, patients who received Triplex also developed CMV immunity 197% higher than patients who received placebo. None of the patients vaccinated with Triplex died because of nonrelapse causes in the first 100 days or had serious adverse events. No grade 3 or 4 vaccine-related adverse events occurred in the first 2 weeks after vaccination.

Diamond emphasized the benefits of the vaccine on the immune system compared with antiviral medication.

“There is a biologic or immunotherapy that could be available in the near future that would replace antiviral prophylactic medications such as Merck’s letermovir (Prevymis) that is required to be taken once daily for 100 days,” Diamond said. “The vaccine would at most be administered three times to the recipient and possibly one time to their donor. The risk for developing resistance to an antiviral drug is eliminated by switching to the vaccine. In addition, the reconstitution of the immune system that the vaccine promotes is a healthy consequence, because antivirals generally do not allow the reconstitution of the immune system that targets the pathogen they are affecting.”

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Diamond also noted that further vaccine research could benefit other subgroups of transplant patients.

“This clinical trial is the first in stem cell transplant for this agent and needs to be followed up with a phase 3 registration trial so the vaccine can be made available to patients with this unmet medical need,” Diamond said. “There are additional patients who we believe will benefit from the Triplex vaccine, which includes the haploidentical transplant recipients that are growing in number annually because of the superior outcomes vs. cord blood transplant and the ease of identifying donors without legal implications that have plagued some cord blood initiatives.”– by Eamon Dreisbach

Reference:

Diamond DJ, et al. Blood. 2015;doi:10.1182/blood.V126.23.3108.3108.

Aldoss I, et al. Ann Intern Med. 2020;doi:10.7326/M19-2511.

Disclosures: Diamond reports grants from Helocyte Inc. and NIH during the conduct of the study. He also reports, grants, personal fees and other support from Helocyte Inc. and nonfinancial support from Pfizer Inc. unrelated to this study. In addition, Diamond reports a patent 8,580,276 with royalties paid to Helocyte and a patent 9,675,689 with royalties paid to Helocyte. Please see the study for the other authors’ relevant financial disclosures.