A small retrospective study of 23 transplant patients has confirmed that CMV hyperimmune globulin (Cytotect®CP) is a safe and effective salvage therapy for patients with cytomegalovirus (CMV) infection after allogeneic hematopoietic cell transplant (allo-HCT).
Cytotect®CP used as salvage therapy resulted in a 78% overall response rate and 70% of all patients cleared CMV infection, according to investigators.
They observed no clinically significant adverse events.
CMV is a major factor contributing to high mortality rates in allo-HCT patients.
And because Cytotect®CP is less toxic than commonly used treatments for CMV infection, investigators suggested that it be used prophylactically in patients known to have a predisposition to CMV infection.
They reported their findings in the journal Bone Marrow Transplantation.
Patient characteristics and methods
All 23 patients transplanted at 8 centers in France were CMV seropositive at the time of transplant, and 70% received the transplant from a CMV serostatus negative donor.
Recipient positivity and donor negativity, the investigators indicated, is a risk factor for developing recurrent CMV infection after allo-HCT.
The patients’ median age was 53, 11 were male and 12 female.
Five patients (22%) received a haploidentical transplant and 14 (61%) from an unrelated donor, which the investigators pointed out is also a known risk factor for developing recurrent CMV infection.
Thirteen (57%) were in complete remission from their underlying disease, 4 (17%) in partial remission, 1 (4%) had stable disease, and 5 (22%) were in relapse or had progressive disease.
Most (83%) had a peripheral blood transplant, 15 (65%) had a reduced intensity conditioning regimen, and 16 (70%) had antithymocyte globulin as part of their conditioning regimen.
All patients received valacyclovir as antiviral prophylaxis prior to receiving Cytotect®CP. The investigators mentioned in the paper that valacyclovir has not been proven to be effective in treating CMV.
They noted that other CMV treatments, such as ganciclovir, foscavir, and dicofovir, cause high levels of toxicity, frequently leading to treatment discontinuation.
Seventeen patients (74%) had a history of graft-versus-host disease (GVHD), and 11 (49%) had active GVHD at the time CMV hyperimmune globulin was administered.
Investigators used quantitative polymerase chain reaction (PCR) to quantify CMV viral load in the blood.
Treatment could begin when patients’ viral load was greater than 3-3.5 log UI/mL, according to the Francophone Society of Bone Marrow Transplantation and Cellular therapy.
Three patients received Cytotect®CP at a prophylaxis dose (200 U/kg/week) to prevent CMV recurrences and 20 as preemptive therapy (400 U/kg on days 1, 4, 8 then 200 U/kg on days 12and 16).
Seven patients (30%) received Cytotect®CP as monotherapy, 5 (22%) in combination with ganciclovir, 5 (22%) in combination with foscavir, 2 (9%) in combination with ganciclovir and foscavir, and 4 (17%) with some other combination.
Investigators restricted their analysis to 100-day overall survival (OS), starting at the beginning of Cytotect®CP treatment to death within 100 days, regardless of the cause of death.
Eighteen patients (78%) responded to Cytotect®CP, and 16 of the responders converted to CMV-PCR negative.
Median time to achieve CMV-PCR response was 15 days (range, 3-51).
Four patients did not respond to therapy, and 1 patient had a non-evaluable response. The latter patient died 13 days after the introduction of Cytotect®CP due to another infection.
Eight patients died within 100 days after initiation of Cytotect®CP. Two deaths were related to CMV and 6 were unrelated.
Four patients who responded to Cytotect®CP experienced CMV relapse between 9 and 49 days after their best response to therapy.
Five responders died within 100 days due to the following causes: GVHD (n = 2), other infection (n = 1), underlying disease (n = 1), and CMV-related causes (n = 1).
Two of the 4 nonresponders died of other infection (n = 1) and GVHD (n = 1).
Investigators estimated the 100-day OS from the start of Cytotect®CP to be 69.6%. They observed no statistical difference (P=0.258) between those who responded (73.7%) and those who didn’t (50.0%).
The investigators believe that Cytotect®CP is an alternative option for treatment of CMV infection because it avoids renal and bone marrow impairment and should be considered as prophylaxis in select patients.
They recommend a large prospective study be conducted to confirm safety and efficacy results of CMV hyperimmune globulin.
Cytotect®CP is authorized in more than 15 countries for the prophylaxis of CMV infection in patients receiving immunosuppressive treatment, particularly transplant recipients.
In French transplant centers, according to the study authors, use of Cytotect®CP is limited to the salvage setting for recurrent or refractory CMV infections and sometimes in combination for CMV pneumonia.
Biotest, the commercializer of Cytotect®CP, provided a grant for this study.