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. 2024 Mar 1;41(1):9-15.
doi: 10.4274/tjh.galenos.2024.2024.0026. Epub 2024 Feb 13.

Real-Life Data on the Efficacy and Safety of Letermovir for Primary Prophylaxis of Cytomegalovirus in Allogeneic Hematopoietic Stem Cell Recipients: A Single-Center Analysis

Martyna Włodarczyk  1 , Agata Wieczorkiewicz-Kabut  1 , Krzysztof Białas  1 , Anna Koclęga  1 , Izabela Noster  1 , Patrycja Zielińska  1 , Grzegorz Helbig  1
Affiliations

Real-Life Data on the Efficacy and Safety of Letermovir for Primary Prophylaxis of Cytomegalovirus in Allogeneic Hematopoietic Stem Cell Recipients: A Single-Center Analysis

Martyna Włodarczyk et al. Turk J Haematol. .

Abstract
in English, Turkish

Objective: Cytomegalovirus (CMV) reactivation is a life-threatening complication after allogeneic hematopoietic stem cell transplantation (HSCT). Introduction of letermovir (LMV) seems to improve post-transplant outcomes, but delayed-onset CMV reactivation still remains a challenge. In this study, we report on our first experience with LMV prophylaxis in 93 CMV-seropositive adult patients receiving HSCT in our center.

Materials and methods: We retrospectively analyzed the data of 93 adult CMV-seropositive recipients receiving LMV as CMV prophylaxis after HSCT for hematological malignancies between 2019 and 2023. The starting LMV dose was 480 mg daily, reduced to 240 mg daily for those receiving cyclosporin A co-administration. CMV DNA in the blood was measured by real-time polymerase chain reaction weekly for the first 2 months after transplantation, then every other week until the end of immunosuppressive treatment. LMV was continued to day +100 or to CMV reactivation.

Results: The median recipient age at the time of transplant was 51 (range: 20-71) years. All patients received grafts from peripheral blood, mostly for acute myeloid leukemia (60%). The median time from transplantation to LMV initiation was 3 (range: 0-24) days. While 55% of patients were transplanted from matched related donors, 32% had unrelated donors and 13% underwent haploidentical HSCT. Four patients (4%) had CMV “blips” while on LMV, but the drug was continued and repeated assays were negative. Only 2 patients (2%) experienced CMV reactivation while on LMV, on days 48 and 34 after HSCT, respectively. Seven patients (7%) developed late-onset CMV reactivation after a median of 124 days after HSCT (range: 118-152 days) and they were successfully treated with ganciclovir. CMV disease was not observed. Grade III-IV acute graft-versus-host disease occurred in 6 patients (6%) during LMV treatment. LMV treatment was free of side effects.

Conclusion: LMV prophylaxis was effective in preventing CMV reactivation with a favorable safety profile. CMV reactivation occurred mostly after LMV discontinuation; thus, extending the duration of prophylaxis beyond 100 days could be beneficial.

Amaç: Sitomegalovirüs (CMV) reaktivasyonu allojenik hematopoetik kök hücre transplantasyonu (HKHT) sonrasında hayatı tehdit eden bir komplikasyondur. Letermovir (LMV) kullanımının nakil sonrası sonuçları iyileştirdiği görülmektedir, ancak gecikmiş başlangıçlı CMV reaktivasyonu hala bir sorun olmaya devam etmektedir. Bu çalışmada, merkezimizde HKHT olan 93 CMV-seropozitif yetişkin hastada LMV profilaksisi ile ilgili ilk deneyimimizi bildiriyoruz.

Gereç ve yöntemler: 2019-2023 yılları arasında hematolojik maligniteler için HKHT sonrası CMV profilaksisi olarak LMV başlanan 93 yetişkin CMV-seropozitif alıcının verilerini retrospektif olarak analiz ettik. Başlangıç LMV dozu günde 480 mg olup siklosporin A ile birlikte uygulananlar için günde 240 mg’a düşürülmüştür. Kandaki CMV DNA’sı gerçek zamanlı polimeraz zincir reaksiyonu ile transplantasyondan sonraki ilk 2 ay boyunca haftada bir, daha sonra immünosupresif tedavinin sonuna kadar iki haftada bir ölçülmüştür. LMV profilaksisi +100. güne kadar veya CMV reaktivasyonuna kadar devam ettirilmiştir.

Bulgular: Nakil sırasındaki ortanca alıcı yaşı 51 (aralık: 20-71) idi. Tüm hastalar, çoğunlukla miyeloid akut lösemi (%60) nedeniyle periferik kandan nakil yapılmıştır. Transplantasyondan LMV başlangıcına kadar geçen medyan süre 3 (aralık: 0-24) gündü. Hastaların %55’ine doku tipi uyumlu akraba vericilerden nakil yapılırken, %32’sine akraba olmayan vericiler ve %13’üne haploidentik HKHT uygulanmıştır. Dört hastada (%4) LMV kullanırken CMV “blips” görüldü, ancak ilaca devam edildi ve tekrarlanan testler negatif çıktı. Sadece 2 hastada (%2) LMV kullanırken, sırasıyla HKHT’den sonraki 34. ve 48. günlerde CMV reaktivasyonu görülmüştür. Yedi hastada (%7) HKHT’den ortanca 124 gün sonra (aralık: 118-152 gün) geç başlangıçlı CMV reaktivasyonu gelişmiş ve bu hastalar gansiklovir ile başarılı bir şekilde tedavi edilmiştir. Bu hastalarda CMV hastalığı gözlenmemiştir. LMV tedavisi sırasında 6 hastada (%6) grade III-IV akut graft-versus-host hastalığı meydana gelmiştir. LMV tedavisi boyunca yan etki görülmemiştir.

Sonuç: LMV profilaksisi, olumlu bir güvenlik profili ile CMV reaktivasyonunu önlemede etkili olmuştur. CMV reaktivasyonu çoğunlukla LMV kesildikten sonra meydana gelmiştir; bu nedenle profilaksi süresinin 100 günün ötesine uzatılması faydalı olabilir.

Keywords: Allogeneic hematopoietic stem cell transplantation; Antiviral prophylaxis; Cytomegalovirus reactivation; Letermovir.

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Conflict of interest statement

Conflict of Interest: No conflict of interest was declared by the authors.

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