Letermovir is an antiviral with a novel mechanism of action, recently received FDA approval for prophylactic treatment against CMV in GVHD patients. In the approved use, letermovir is administered through week 14 which is about 100 days post-transplant of the allograft. This slideset discusses the subsequent study in which letermovir is investigated for its efficacy when administered beyond weak 14 or 100 days, i.e., extended course letermovir prophylaxis.

1. Cohort Study of Twenty Patients on
Extended Administration of Letermovir
as CMV Prophylaxis in Graft-versus-Host
Disease (GVHD)
Vijay Elipay
(MS Pharmacology & Toxicology, NIPER)
Assistant Professor, MRCP

2. Contents
Background
Methods
Baseline patient characteristics in the cohort
study
Baseline differences among the patients with
respect to GVHD
Baseline differences among patients on
extended administration of letermovir
Results
Summary
2
1
3
4
5
6
7
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3. Background
 Cytomegalovirus (CMV) reactivation
results in significant morbidity and
mortality after an allogeneic
hematopoietic cell transplant (AHCT).1
• Graft-versus-host disease (GVHD)
increases the risk of CMV reactivation.
 Letermovir is an inhibitor of the CMV DNA
terminase complex.
• It is FDA approved for CMV prophylaxis in CMV
seropositive patients through week 14 (~100
days) post transplantation following a
randomized, phase 3, double-blind trial.2
 Letermovir’s efficacy in preventing CMV in
patients with GVHD requiring treatment
beyond the 100 days must be studied.
1. Schmidt-Hieber M, Tridello G, Ljungman P, et al. The prognostic impact of the cytomegalovirus serostatus in
patients with chronic hematological malignancies after allogeneic hematopoietic stem cell transplantation: a
report from the Infectious Diseases Working Party of EBMT. Annals of Hematology. 2019;98(7):1755-1763.
doi:10.1007/s00277-019-03669-z
2. Marty FM, Ljungman P, Chemaly RF, et al. Letermovir Prophylaxis for Cytomegalovirus in Hematopoietic-Cell
Transplantation. New England Journal of Medicine. 2017;377(25):2433-2444. doi:10.1056/nejmoa1706640

4. Methods (Study Design)
1. Bansal R, Gordillo CA, Abramova R, et al. Extended letermovir administration, beyond day 100, is effective for CMV prophylaxis in patients with graft versus host
disease. Transplant Infectious Disease. 2020;23(2). doi:10.1111/tid.13487
 Retrospective Cohort Study of ~24 months from a Single Center1
All patients who
received AHCT
between Jan 2018
and Jan 2020, who
were CMV
seropositive prior
to transplant and
received
letermovir for
CMV prophylaxis
(n = 36)
Letermovir 480 mg OD
(PO or IV), starting day 5
after stem cell infusion
and extended beyond
100 days (n = 19)
Letermovir 240 mg OD,
starting day 5 after stem
cell infusion and
extended beyond 100
days (n = 1)
in patients receiving
cyclosporine for GVHD
prophylaxis
Letermovir >100 days
(n = 20)
Incidence of
clinically
significant
CMV
infection*
*Primary end point: Incidence
of clinically significant CMV
infection, i.e.,
1. onset of CMV disease or
2. initiation of preemptive
therapy with alternative
antiviral agents.
Abbreviations: AHCT – allogeneic hematopoietic
cell transplant; CMV – Cytomegalovirus; GVHD –
Graft-versus-Host Disease; OD – once daily; PO –
per oral; IV – intravenous.

5. Baseline Patient Characteristics in the Cohort Study1
Total number of patients: n 20
Median age, years (range) 54 (21 – 72)
Donor/Recipient CMV status: n (%)
D-/R+ 5 (25)
D+/R+ 15 (75)
Disease: n (%)
Myeloid neoplasm 12 (60)
Lymphoid neoplasm 5 (25)
Sickle Cell disease 3 (15)
Donor Source: n (%)
Matched related 7 (35)
Matched unrelated 7 (35)
Haploidentical 5 (25)
Mismatched unrelated 1 (5)
Conditioning intensity: n (%)
Myeloablative 14 (70)
Reduced Intensity 6 (30)
Abbreviations: GVHD – Graft-versus-Host Disease; D – Donor; R – Recipient; CMV – Cytomegalovirus.
1. Bansal R, Gordillo CA, Abramova R, et al. Extended letermovir administration, beyond day 100, is effective for CMV prophylaxis in patients with graft versus host disease. Transplant
Infectious Disease. 2020;23(2). doi:10.1111/tid.13487

6. Baseline Differences Among the Patients with respect
to GVHD1
GVHD prophylaxis: n (%)
Tac/MTX 9 (45)
Tac/MMF/PTCy 6 (30)
Alemtuzumab/Sirolimus 3 (15)
Tac/MMF 2 (10)
Median time to onset of first
episode of GVHD, days (range)
All patients 30 (12 – 190)
In patients with CMV ≥ 150 IU/ml while on
letermovir after GVHD diagnosis
27 (20 – 31)
In patients with CMV < 150 IU/ml while on
letermovir after GVHD diagnosis
36 (12-190)
Type of GVHD: n (%)
Acute GVHD grade 2-4 18 (90)
Acute GVHD grade 1 1 (5)
Chronic GVHD 4 (20)
GVHD treatment: n (%)
Systemic glucocorticoids 17 (85)
Budesonide or topical corticosteroids only 3 (15)
Abbreviations: w.r.t. – with respect to; GVHD – Graft-versus-Host Disease; Tac – Tacrolimus; MTX – Methotrexate; MMF – Mycophenolate
Mofetil; PTCy – Post-Transplant Cyclophosphamide.
1. Bansal R, Gordillo CA, Abramova R, et al. Extended letermovir administration, beyond day 100, is effective for CMV prophylaxis in patients with graft versus host disease. Transplant
Infectious Disease. 2020;23(2). doi:10.1111/tid.13487

7. Baseline Differences Among the Patients on Extended
Administration of Letermovir1
Median duration of follow up, days (range) 208 (113 – 826)
Median duration of letermovir treatment post-transplant, days (range) 182 (107 – 576+)
Median duration of letermovir treatment after GVHD diagnosis, days (range) 147 (43 – 470+)
Median CD4 count at 1 mo (+/-3 wks)
after the diagnosis of GVHD, cells/µL
(range)
All patients 98 (15-372)
In patients with CMV ≥ 150 IU/ml while
on letermovir after GVHD diagnosis
24 (19 – 92)
In patients with CMV < 150 IU/ml while
on letermovir after GVHD diagnosis
139 (15 – 372)
Patients receiving PTCy 29 (19 - 92)
Patients not receiving PTCy 188 (15 – 372)
Abbreviations: CMV – Cytomegalovirus, GVHD – Graft-versus-Host Disease; PTCy – Post-Transplant Cyclophosphamide.
1. Bansal R, Gordillo CA, Abramova R, et al. Extended letermovir administration, beyond day 100, is effective for CMV prophylaxis in patients with graft versus host disease. Transplant
Infectious Disease. 2020;23(2). doi:10.1111/tid.13487

8. Results1
 Only 1 patient (5%) developed a clinically
significant CMV infection (primary end
point) with a peak viremia of 3890 IU/mL.
• Preemptive therapy included
valganciclovir and foscarnet.
 No patients developed CMV organ disease.
 Three additional patients developed CMV
viremia of ≥ 150 IU/mL while on letermovir
and after the onset of GVHD.
• However, none required switching
antivirals.
 Post-transplant cyclophosphamide and
low CD4 count after the development of
GVHD were associated with the high CMV
viral load while on extended duration
letermovir.
1. Bansal R, Gordillo CA, Abramova R, et al. Extended letermovir administration, beyond day 100, is effective for
CMV prophylaxis in patients with graft versus host disease. Transplant Infectious Disease. 2020;23(2).
doi:10.1111/tid.13487

9. Individual Patient's Clinical Course for All 20 Patients1
1. Bansal R, Gordillo CA, Abramova R, et al. Extended letermovir administration, beyond day 100, is effective for CMV prophylaxis in patients with graft versus host disease. Transplant
Infectious Disease. 2020;23(2). doi:10.1111/tid.13487
Duration of letermovir treatment and severity of CMV infection are represented by
different colour patterns as noted. Onset of GVHD is also noted. The
immunosuppressive treatment for GVHD is listed above the bar, including the
starting dose of systemic steroids.
Abbreviations: CMV – Cytomegalovirus; GVHD – Graft-
versus-Host Disease; P – Prednisolone; MP –
Methylprednisolone; B – Budesonide; C – Cyclosporine; PTCy
– Post-transplant Cyclophosphamide; Al – Alemtuzumab.

10. Summary
 A retrospective cohort study of extended
(beyond 100 days) letermovir prophylaxis
was done in 20 patients with graft-versus-
host disease (GVHD).
• Only 1 patient developed a clinically
significant infection (primary end
point).
• Total 4 patients (20%) with acute
GVHD developed CMV viremia ≥ 150
IU/mL.
• Only patients that received post-
transplant cyclophosphamide (PTCy)
developed CMV viremia ≥150 IU/mL.
 Therefore, an extended prophylactic
course of letermovir may help patients to
mount an immune response against CMV,
despite ongoing immunosuppressive
therapy.

11. Thank You!