Valacyclovir after allogeneic HCT reduces CMV infection

Viral prophylaxis with valacyclovir 1 g three times daily following allogeneic haematopoietic cell transplantation (HCT) results in a lower incidence of clinically significant cytomegalovirus (CMV) infection as compared with acyclovir, according to a study.

In addition, “[v]alacyclovir does not present the challenges of poor tolerability and high cost associated with alternative prophylactic options and has the potential to benefit patients on a broad scale as an accessible and affordable option for CMV prophylaxis,” the researchers said.

In this retrospective study, the research team reviewed medical records to compare the incidence of clinically significant CMV infection (CMV disease or reactivation requiring pre-emptive treatment) following allogeneic HCT between patients treated with valacyclovir 1 g three times daily and those receiving acyclovir 400 mg every 12 h for viral prophylaxis.

Forty-five patients on valacyclovir were propensity-score matched to 35 patients on acyclovir. All patients were treated with reduced-intensity conditioning regimens containing antithymocyte globulin (ATG). [J Oncol Pharm Pract 2023:doi:10.1177/10781552211060479]

By day 180 after HCT, patients in the valacyclovir group showed a lower rate of clinically significant CMV infection than those in the acyclovir group (18 percent vs 57 percent; p=0.0004). Patients who received valacyclovir also had less severe infection as shown by a decrease in CMV disease, lower peak CMV titres, delayed CMV reactivation, and fewer occurrence of secondary neutropaenia.

When compared to previous studies of valacyclovir for CMV prophylaxis, the current regimen resulted in a lower pill burden, used a generally accepted dose and frequency from a cost perspective, and did not have any major toxicity associated with it. [Blood 2002;8:3050-3056]

“Overall, the incidence of CMV reactivation observed in the valacyclovir group was lower than in controls,” the researchers said. “Further, when reactivation did occur, it occurred later, was not as severe, did not cause CMV disease, and was associated with fewer complications.”

CMV reactivation

When weighing the costs and benefits of using CMV prophylaxis, patient risk factors for CMV reactivation must also be considered, according to the researchers.

For instance, an earlier retrospective study reported the benefit of letermovir prophylaxis in patients at high risk for CMV reactivation, including recipients of haploidentical transplant, umbilical cord blood transplant, those with mismatched donors, and those receiving ATG as part of their conditioning regimen. [Biol Blood Marrow Transplant 2020;26:1963-1970]

Additionally, the current study showed the association of valacyclovir use with a decrease in secondary neutropaenia in patients treated with CMV pre-emptive therapy.

“This finding may be due to the … potential for valacyclovir prophylaxis to delay CMV reactivation to a time when patients can better tolerate the myelosuppression associated with valganciclovir or ganciclovir,” the researchers said.

Of note, none of the patients receiving valacyclovir required treatment with foscarnet as compared with three in the acyclovir group who required such therapy (15 percent of patients with CMV reactivation).

“Prospective evaluation of valacyclovir 1 g three times daily for viral prophylaxis following allogeneic HCT is warranted,” the researchers said. “Due to valacyclovir's favorable toxicity profile and affordable cost, it has the potential to benefit patients on a broad scale as an option for CMV prophylaxis.”