1897. Letermovir Salvage for Complicated Cases of Resistant CMV
Session: Poster Abstract Session: Antiviral Therapies
Saturday, October 6, 2018
Room: S Poster Hall
Posters
  • Letermovir Case Series Poster FINAL.pdf (344.6 kB)
  • Background:

    Limited treatment options exist for ganciclovir-resistant CMV disease. Foscarnet can cause renal insufficiency, and maribavir has poor ocular penetration. Letermovir is approved for primary CMV prophylaxis in hematopoietic stem cell transplantation, but efficacy in treatment of CMV disease or secondary prophylaxis is not known.

    Methods:

    We analyzed data from all adult patients at a single center who initiated letermovir for treatment of CMV disease or secondary prophylaxis of CMV retinitis from 11/2017 through 4/2018. We described patient characteristics, extent of CMV disease, prior antiviral therapies, kinetics of CMV DNAemia, and clinical outcomes.

    Results:

    Four patients received letermovir for treatment, and one for secondary suppression, of CMV DNAemia and CMV retinitis (Table).  All patients had proven genotypic resistance with complications and/or clinical failure on prior antivirals. Letermovir doses ranged from 480mg to 720mg daily. 3 patients received concomitant CMV immune globulin and intravitreal therapy with foscarnet and/or ganciclovir. No patients developed side effects attributable to letermovir, and expected increases in tacrolimus levels occurred. All 5 patients demonstrated clinical and retinoscopic improvement (Figure 1), but two patients did not achieve complete resolution of DNAemia (Figure 2).

    Conclusion:

    Use of letermovir, often in combination with intravitreal therapy, was associated with sustained clinical improvement in 5 patients with CMV retinitis. Treatment doses of up to 720mg were well tolerated. Despite marked improvement of ocular disease, two patients did not achieve sustained suppression of DNAemia.

    Table. Patient characteristics

    A. 66 y.o. male

    B. 50 y.o. male

    C. 46 y.o. male

    D. 66 y.o. male

    E. 43 y.o. female

    CMV risk factor(s)

    Lung txp

    Lung txp

    Heart txp

    Heart txp

    Susac syndrome

    Disease burden

    CMV syndrome

     Retinitis

    CMV syndrome Retinitis

    CMV syndrome

    Retinitis

    Colitis

    Retinitis

    Retinitis

    Previous antivirals

    C, G/V, M, F

    G/V, F, M

    G/V, F

    C, G/V, F

    G, F

    CMV mutations

    M460V

    Q578H

    M460I

    H520Q, C603W, T503I

    A594V

    Current letermovir duration (weeks)

    9.5

    9.5

    7

    5

    26*

    *Secondary prophylaxis only

    C, CMV Immune globulin; F, foscarnet; G, ganciclovir; M, maribavir; txp, transplant; V, valganciclovir

    Nicholas Turner, MD1, Andrew Strand, MD1, Jennifer Saullo, MD, PharmD1, Sana Arif, MBBS1, Eileen K. Maziarz, MD1, Dilraj Grewal, MD2, Arthur W. Baker, MD, MPH3 and Cameron R. Wolfe, MBBS (Hons), MPH, FIDSA1, (1)Division of Infectious Diseases, Duke University Medical Center, Durham, NC, (2)Ophthalmology, Duke University Medical Center, durham, NC, (3)Division of Infectious Diseases, Duke University School of Medicine, Durham, NC

    Disclosures:

    N. Turner, None

    A. Strand, None

    J. Saullo, None

    S. Arif, None

    E. K. Maziarz, None

    D. Grewal, None

    A. W. Baker, None

    C. R. Wolfe, Merck: Scientific Advisor , Consulting fee .

    Findings in the abstracts are embargoed until 12:01 a.m. PDT, Wednesday Oct. 3rd with the exception of research findings presented at the IDWeek press conferences.