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An antiviral agent can reduce the incidence of cytomegalovirus (CMV) infection in patients receiving an allogeneic hematopoietic stem cell
transplant, according to a study published in The New England Journal of Medicine.
The agent, letermovir, proved more effective than placebo in preventing CMV, and the highest dose tested, 240 mg/day, was most effective.
The most common adverse events were gastrointestinal disorders and infections.
However, the incidence of events was similar among treated patients and those in the placebo arm.
Roy F. Chemaly, MD, of the University of Texas MD Anderson Cancer Center in Houston, and his colleagues conducted this randomized, double-blind, phase 2 trial. It was funded by AiCuris, the company that was developing letermovir before Merck purchased worldwide rights to develop and commercialize the drug in 2012.
The researchers evaluated the effect of letermovir on the incidence and time-to-onset of CMV prophylaxis failure in CMV-seropositive, matched transplant recipients.
The study included 131 patients. For 12 weeks after engraftment, they received placebo (n=33) or letermovir at 60 mg/day (n=33), 120 mg/day (n=31), or 240 mg/day (n=34).
Efficacy analysis
The primary endpoint was all-cause prophylaxis failure, which was defined as discontinuation of the study drug due to CMV antigen or CMV DNA detection, end-organ disease, or any other causes unrelated to CMV.
The primary efficacy analysis population was a modified intention-to-treat population, which included all patients who received at least 1 dose of the study drug and had at least 1 measurement of the CMV viral load during the study.
The incidence of all-cause prophylaxis failure was significantly lower in the groups that received letermovir at doses of 120 mg/day or 240 mg/day, when compared with the placebo group—32% and 29% vs 64%; P=0.01 and P=0.007, respectively.
The time to the onset of prophylaxis failure was significantly shorter in the 240-mg group (range, 1 to 8 days) than in the placebo group (range, 1 to 21 days; P=0.002).
However, comparisons with the placebo group were not significant for the 60-mg group (range, 1 to 42 days; P=0.15) or the 120-mg group (range, 1 to 15 days; P=0.13).
The incidence of virologic failure was lower in the 240-mg group (6%) than in the 120-mg group (19%), the 60-mg group (21%), or the placebo group (36%).
Virologic failure was defined as either detectable CMV antigen or DNA in the blood at 2 consecutive time points (with at least 1 instance confirmed by the central lab), leading to discontinuation of the study drug and the administration of rescue medication or the development of CMV end-organ disease.
Safety analysis
Nearly all of the patients had at least 1 adverse event during treatment—94% in the 60-mg and 120-mg groups and 100% in the 240-mg and placebo groups. Most events were mild or moderate.
However, 24% of letermovir-treated patients and 30% of those who received placebo experienced severe adverse events during treatment. Investigators, who were blinded to treatment, considered 17% of the severe events in the letermovir group to be drug-related and 33% of severe events in the placebo group to be drug-related.
Most adverse events were gastrointestinal disorders—diarrhea, nausea, and vomiting—which occurred in 66% of letermovir-treated patients and 61% of patients in the placebo group. Infections—mostly CMV—were also common, occurring in 59% of letermovir-treated patients and 76% of patients in the placebo group.
Five patients died during the trial. None of the deaths were thought to be related to treatment or to CMV. 
An antiviral agent can reduce the incidence of cytomegalovirus (CMV) infection in patients receiving an allogeneic hematopoietic stem cell
transplant, according to a study published in The New England Journal of Medicine.
The agent, letermovir, proved more effective than placebo in preventing CMV, and the highest dose tested, 240 mg/day, was most effective.
The most common adverse events were gastrointestinal disorders and infections.
However, the incidence of events was similar among treated patients and those in the placebo arm.
Roy F. Chemaly, MD, of the University of Texas MD Anderson Cancer Center in Houston, and his colleagues conducted this randomized, double-blind, phase 2 trial. It was funded by AiCuris, the company that was developing letermovir before Merck purchased worldwide rights to develop and commercialize the drug in 2012.
The researchers evaluated the effect of letermovir on the incidence and time-to-onset of CMV prophylaxis failure in CMV-seropositive, matched transplant recipients.
The study included 131 patients. For 12 weeks after engraftment, they received placebo (n=33) or letermovir at 60 mg/day (n=33), 120 mg/day (n=31), or 240 mg/day (n=34).
Efficacy analysis
The primary endpoint was all-cause prophylaxis failure, which was defined as discontinuation of the study drug due to CMV antigen or CMV DNA detection, end-organ disease, or any other causes unrelated to CMV.
The primary efficacy analysis population was a modified intention-to-treat population, which included all patients who received at least 1 dose of the study drug and had at least 1 measurement of the CMV viral load during the study.
The incidence of all-cause prophylaxis failure was significantly lower in the groups that received letermovir at doses of 120 mg/day or 240 mg/day, when compared with the placebo group—32% and 29% vs 64%; P=0.01 and P=0.007, respectively.
The time to the onset of prophylaxis failure was significantly shorter in the 240-mg group (range, 1 to 8 days) than in the placebo group (range, 1 to 21 days; P=0.002).
However, comparisons with the placebo group were not significant for the 60-mg group (range, 1 to 42 days; P=0.15) or the 120-mg group (range, 1 to 15 days; P=0.13).
The incidence of virologic failure was lower in the 240-mg group (6%) than in the 120-mg group (19%), the 60-mg group (21%), or the placebo group (36%).
Virologic failure was defined as either detectable CMV antigen or DNA in the blood at 2 consecutive time points (with at least 1 instance confirmed by the central lab), leading to discontinuation of the study drug and the administration of rescue medication or the development of CMV end-organ disease.
Safety analysis
Nearly all of the patients had at least 1 adverse event during treatment—94% in the 60-mg and 120-mg groups and 100% in the 240-mg and placebo groups. Most events were mild or moderate.
However, 24% of letermovir-treated patients and 30% of those who received placebo experienced severe adverse events during treatment. Investigators, who were blinded to treatment, considered 17% of the severe events in the letermovir group to be drug-related and 33% of severe events in the placebo group to be drug-related.
Most adverse events were gastrointestinal disorders—diarrhea, nausea, and vomiting—which occurred in 66% of letermovir-treated patients and 61% of patients in the placebo group. Infections—mostly CMV—were also common, occurring in 59% of letermovir-treated patients and 76% of patients in the placebo group.
Five patients died during the trial. None of the deaths were thought to be related to treatment or to CMV.
An antiviral agent can reduce the incidence of cytomegalovirus (CMV) infection in patients receiving an allogeneic hematopoietic stem cell
transplant, according to a study published in The New England Journal of Medicine.
The agent, letermovir, proved more effective than placebo in preventing CMV, and the highest dose tested, 240 mg/day, was most effective.
The most common adverse events were gastrointestinal disorders and infections.
However, the incidence of events was similar among treated patients and those in the placebo arm.
Roy F. Chemaly, MD, of the University of Texas MD Anderson Cancer Center in Houston, and his colleagues conducted this randomized, double-blind, phase 2 trial. It was funded by AiCuris, the company that was developing letermovir before Merck purchased worldwide rights to develop and commercialize the drug in 2012.
The researchers evaluated the effect of letermovir on the incidence and time-to-onset of CMV prophylaxis failure in CMV-seropositive, matched transplant recipients.
The study included 131 patients. For 12 weeks after engraftment, they received placebo (n=33) or letermovir at 60 mg/day (n=33), 120 mg/day (n=31), or 240 mg/day (n=34).
Efficacy analysis
The primary endpoint was all-cause prophylaxis failure, which was defined as discontinuation of the study drug due to CMV antigen or CMV DNA detection, end-organ disease, or any other causes unrelated to CMV.
The primary efficacy analysis population was a modified intention-to-treat population, which included all patients who received at least 1 dose of the study drug and had at least 1 measurement of the CMV viral load during the study.
The incidence of all-cause prophylaxis failure was significantly lower in the groups that received letermovir at doses of 120 mg/day or 240 mg/day, when compared with the placebo group—32% and 29% vs 64%; P=0.01 and P=0.007, respectively.
The time to the onset of prophylaxis failure was significantly shorter in the 240-mg group (range, 1 to 8 days) than in the placebo group (range, 1 to 21 days; P=0.002).
However, comparisons with the placebo group were not significant for the 60-mg group (range, 1 to 42 days; P=0.15) or the 120-mg group (range, 1 to 15 days; P=0.13).
The incidence of virologic failure was lower in the 240-mg group (6%) than in the 120-mg group (19%), the 60-mg group (21%), or the placebo group (36%).
Virologic failure was defined as either detectable CMV antigen or DNA in the blood at 2 consecutive time points (with at least 1 instance confirmed by the central lab), leading to discontinuation of the study drug and the administration of rescue medication or the development of CMV end-organ disease.
Safety analysis
Nearly all of the patients had at least 1 adverse event during treatment—94% in the 60-mg and 120-mg groups and 100% in the 240-mg and placebo groups. Most events were mild or moderate.
However, 24% of letermovir-treated patients and 30% of those who received placebo experienced severe adverse events during treatment. Investigators, who were blinded to treatment, considered 17% of the severe events in the letermovir group to be drug-related and 33% of severe events in the placebo group to be drug-related.
Most adverse events were gastrointestinal disorders—diarrhea, nausea, and vomiting—which occurred in 66% of letermovir-treated patients and 61% of patients in the placebo group. Infections—mostly CMV—were also common, occurring in 59% of letermovir-treated patients and 76% of patients in the placebo group.
Five patients died during the trial. None of the deaths were thought to be related to treatment or to CMV.