Francisco M. Marty, MD, and Kathleen Mullane, DO, PharmD, FIDSA, prepared useful Practice Aids pertaining to cytomegalovirus management for this CME activity titled "Refining the Management of CMV in HCT Recipients: What Does the Future Hold?" For the full presentation, monograph, complete CME information, and to apply for credit, please visit us at http://bit.ly/2uk5G0q. CME credit will be available until April 3, 2019.

1. Access the activity,“Refining the Management of CMV in HCT Recipients:
What Does the Future Hold?”at www.peerview.com/RKC40.
CMV: The Most Common
Clinically Significant Viral
Infection Among HCT Recipients
PRACTICE AID
This Practice Aid has been provided as a quick reference to help learners apply the information to their daily practice and care of patients.
CMV: cytomegalovirus; GVHD: graft versus host disease; HCT: hematopoietic cell transplantation; R: recipient.
1. Azevedo LS et al. Clinics (Sao Paulo). 2015;70:515-523. 2. Boeckh M, Ljungman P. Blood. 2009;113:5711-5719. 3. Ljungman P et al. Clin Infect Dis. 2002;34:1094-1097.
Definitions1
Latent CMV
Active CMV infection
CMV disease
Virus persists in a latent state
Evidence of CMV replication
CMV infection with organ
damage, clinical symptoms
Risk Factors for CMV Reactivation2
• Multiorgan disease
(eg, pneumonia, hepatitis,
gastroenteritis, retinitis,
encephalitis)
• Can develop both
early and late after
the transplantation
procedure
Direct Effects2
• Allograft rejection:
acute, chronic
• Accelerated
atherosclerosis
• Fungal and bacterial
infections
Indirect Effects3
• CMV seropositive recipient (R+)
• HLA mismatched or haploidentical donors
• Use of cord blood as stem-cell source or grafts
• T-cell depletion
• GVHD and treatment with corticosteroids
• Use of antithymocyte globulin or alemtuzumab
!

2. This Practice Aid has been provided as a quick reference to help learners apply the information to their daily practice and care of patients.
New Approaches to Preventing
and Treating CMV Infection
in the HCT Setting
PRACTICE AID
Access the activity,“Refining the Management of CMV in HCT Recipients: What Does the Future Hold?”
at www.peerview.com/RKC40.
Agent
Mechanism
of Action
Route of
Administration
Phase of
Developmenta Setting Strategy Efficacy Side Effects
Letermovir
Inhibits
terminase
complex (UL51,
UL56, UL89)
Oral/IV APPROVED HCT Prophylaxis
Letermovir prophylaxis resulted in
a significantly lower risk of clinically
significant CMV infection than placebo1
Nausea,
vomiting
Maribavir
Inhibits CMV
protein-kinase
UL97-mediated
nuclear egress
Oral
2
HCT
SOT Preemptive
treatment
Comparable rates of patients achieving
undetectable CMV DNA within 6 weeks
with maribavir and valganciclovir2
Dysgeusia,
nausea,
vomiting
Currently recruiting participants
(NCT02927067)3 HCT
2
HCT
SOT
Refractory/
resistant
CMV
infection
Within 6 weeks, 67% of patients
had undetectable plasma CMV DNA3
3
HCT
SOT
Currently recruiting participants
(NCT02931539)
Novel Anti-CMV Drugs

3. New Approaches to Preventing
and Treating CMV Infection
in the HCT Setting
a
Accurate as of January 25, 2018.
CMV: cytomegalovirus; HCMV: human CMV; HCT: hematopoietic cell transplantation; mAbs: monoclonal antibodies; MVA: modified vaccinia Ankara; SOT: solid organ transplantation.
1. Marty FM et al. N Engl J Med. 2017;377:2433-2444. 2. Maertens JA et al. 2017 BMT Tandem Meetings (BMT 2017). Abstract 229. 3. Papanicolaou G et al. BMT 2017. Abstract 45. 4. Kharfan-Dabaja MA et al. Lancet Infect Dis. 2012;12:290-299. 5. https://newsroom.astellas.us/
2018-01-22-Astellas-and-Vical-Announce-Top-Line-Results-for-Phase-3-Trial-of- Cytomegalovirus-Vaccine-ASP0113-in-Hematopoietic-Stem-Cell-Transplant-Recipients. Accessed January 25, 2018. 6. Nakamura R et al. Lancet Haematol. 2016;3:e87-e98.
7. https://clinicaltrials.gov/ct2/show/NCT02396134. Accessed January 11, 2018. 8. Walsh SR et al. J Infect Dis. 2013;207:1888-1897. 9. http://www.bbmt.org/article/S1083-8791(16)00030-6/fulltext. Accessed January 11, 2018. 10. https://clinicaltrials.gov/ct2/show/
NCT02506933. Accessed January 11, 2018. 11. https://clinicaltrials.gov/ct2/show/ NCT02268526. Accessed January 11, 2018. 12. http://aac.asm.org/content/61/2/e01794-16.abstract. Accessed January 11, 2018.
PRACTICE AID
Access the activity,“Refining the Management of CMV in HCT Recipients: What Does the Future Hold?”
at www.peerview.com/RKC40.
Other Novel Approaches in Development
Agent/
Approach
Mechanism of Action
Phase of
Development
Comments
ASP0113 CMV DNA vaccine 3
In a phase 2 trial, ASP0113 significantly reduced the occurrence and recurrence
of CMV viremia and improved the time-to-event for viremia episodes
compared with placebo; ASP0113 was well tolerated4
Multinational phase 3 registration trial in HCT recipients (HELIOS)
completed October 2017; ASP0113 did not meet primary or secondary endpoints5
PepVax CMV peptide vaccine 2
Safety and immunogenicity of the PepVax vaccine demonstrated in a phase 1b trial6
Phase 2 trial underway to evaluate vaccine therapy in reducing the frequency of CMV
events in patients with hematologic malignancies undergoing donor stem cell transplant7
Triplex
Multi-antigen CMV-MVA
triplex vaccine
2
Encouraging safety and immunogenicity data generated in a phase 1b trial8,9
Phase 2 trial underway to evaluate Triplex in reducing CMV complications
in patients previously infected with CMV and undergoing donor HCT10
CSJ148
Combination of two
anti-HCMV human mAbs
(LJP538 and LJP539)
1/2
Phase 1/2 trial completed to assess the efficacy and safety of CSJ148
in stem cell transplant patients11
RG7667
Combination of two mAbs,
MCMV5322A and
MCMV3068A
2
In a phase 2 trial of high-risk kidney transplant recipients, RG7667 was well tolerated,
numerically reduced the incidence of CMV infection within 12 and 24 weeks post-transplant,
delayed time to CMV viremia, and was associated with less CMV disease than the placebo12