Randomized, placebo-controlled, double-blind study of a cytomegalovirus-specific monoclonal antibody (MSL-109) for prevention of cytomegalovirus infection after allogeneic hematopoietic stem cell transplantation

MSL-109 is a monoclonal antibody specific to the cytomegalovirus (CMV) glyc oprotein H with high neutralizing capacity. In a prospective, randomized, d ouble-blind study allogeneic hematopoietic stem cell transplantation (HSCT) recipients with positive donor and/or recipient serology for CMV before tr ansplantation received either 60 mg/kg MSL-109 (n = 59), 15 mg/kg MSL-109 ( n = 60), or placebo (n = 60) intravenously every 2 weeks from day -1 until day 84 after transplantation. CMV pp65 antigenemia, CMV-DNA load in plasma, and viremia by culture were tested weekly. Primary end points were develop ment of pp65 antigenemia at any level and/or viremia for which ganciclovir was given. There was no statistically significant difference in CMV pp65 an tigenemia or viremia among patients in the 60-mg group (pp65 antigenemia, 4 7%; viremia, 15%), the 15-mg group (52%; 23%), and the placebo group (45%; 17%). There was also no difference in maximum levels of pp65 antigenemia, t ime to clearance of pp65 antigenemia after start of ganciclovir, CMV diseas e, invasive bacterial and fungal infections, time to neutrophil and platele t engraftment, acute graft-versus-host disease, days of hospitalization, an d overall survival rate among the 3 groups. However, a subgroup analysis of CMV-seronegative recipients with a seropositive donor (D+/R-) showed a tra nsiently improved survival rate by day 100 in MSL-109 recipients (mortality : 60-mg group, 1/13; 15-mg group, 1/12; placebo group, 6/10 [P = .02 for 60 -mg versus placebo groups; P = .08 for 15-mg versus placebo groups]); by th e end of follow-up, the difference was no longer statistically significant. Tile improved survival rate in D+/R- patients could not be attributed to a reduction in CMV disease; however, MSL-109 was associated with improved pl atelet engraftment and less grade III to IV acute graft-versus-host disease in this subgroup. In a subgroup analysis of CMV-seropositive recipients of MSL-109 (D+/R+ and D-/R+), overall mortality was increased compared to tha t of the placebo group (P = .12 for the 60-mg versus placebo groups, P = .0 5 for the 15-mg versus placebo groups, and P = .04 for the dose levels comb ined versus placebo). MSL-109 was well tolerated and no immune response to the drug was observed. Thus, MSL-109 was safe but did not reduce CMV infect ion in allogeneic HSCT recipients. The transient survival advantage seen ea rly after transplantation in CMV D+/R- patients and the negative effect on survival in seropositive patients remain unexplained. Thus, there is no evi dence that MSL-109 is beneficial in CMV-seropositive HSCT recipients.