Final Results of a Phase 2, Single Arm Trial Evaluating Letermovir for Cytomegalovirus Prophylaxis in Patients with Hematological Malignancies Treated with Alemtuzumab

Cytomegalovirus (CMV) reactivation is a common complication in immunocompromised patients, including those treated with alemtuzumab. Letermovir is a potent antiviral approved CMV prophylaxis following allogeneic bone marrow transplantation. This trial aimed to investigate the efficacy of letermovir in preventing CMV reactivation in patients treated with alemtuzumab.

This was a single arm trial that included patients with hematologic malignancies treated with alemtuzumab who were seropositive for prior CMV exposure (IgG positive). Patients began letermovir 480 mg daily within 14 days of starting alemtuzumab and continued through 3 months after the last dose of alemtuzumab. The primary objective was to estimate the rate of CMV reactivation while on letermovir. CMV PCR was performed at least every 2 weeks during the study period.

The trial enrolled six patients. The median age was 74 (56-80) and 50% were male. Four patients (66.7%) had T-cell prolymphocytic leukemia, one patient (16.7%) had Sezary syndrome, and one patient (16.7%) had erythrodermic mycosis fungoides.

None of the patients enrolled experienced CMV reactivation during the study period. The most common adverse events of grade 3 or higher at least possibly attributable to letermovir included thrombocytopenia (50%), leukopenia (33.3%), anemia, diarrhea, prolonged APTT, elevated alkaline phosphatase, lymphopenia, neutropenia, and sinus bradycardia (16.7% each).

The trial was closed prior to completing accrual due to low enrollment, limiting the ability to draw definitive conclusions. Overall, the trial showed that letermovir may be effective in preventing CMV reactivation in patients treated with alemtuzumab. Further research in a larger trial is needed to validate these findings.

Reneau:Incyte: Research Funding; Merck: Research Funding; Mescape: Honoraria; Kymera Therapeutics: Research Funding; Celgene: Research Funding; Acrotech biopharma: Consultancy; Corvus Pharmaceuticals: Research Funding; Kyowa Kirin: Research Funding. Brammer:Incyte: Other: Trial Support, Research Funding; Secura Bio, INc.: Consultancy.

Letermovir off label use