Airway and Lung Infection, Thoracic Surgery and Transplantation CE/CME ACCREDITED Watch Time: 33 Mins

touchEXPERT OPINIONS Cytomegalovirus in solid organ transplant recipients: Management strategies and emerging therapeutic options

Watch experts give their perspectives on management challenges, antiviral options and best practice in treating cytomegalovirus in solid organ transplant recipients.

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Dr Camille Kotton
Massachusetts General Hospital, Boston, MA, USA
Management challenges in solid organ transplant recipients with cytomegalovirus

Dr Camille Kotton outlines the risk of CMV in solid organ transplant recipients, preventative strategies, current antiviral treatment options and management of antiviral resistance

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In this interview, Dr Kotton answers the following questions:

  • What is the risk of CMV for solid organ transplant recipients?
  • What strategies can be employed to prevent CMV infection in solid organ transplant recipients?
  • What are the current treatment options for solid organ transplant recipients with CMV infection?
  • What are the implications for antiviral resistance in CMV infection for solid organ transplant recipients?

Camille Nelson Kotton MD, FIDSA, FAST is the clinical director of the Transplant Infectious Disease and Immunocompromised Host Program at the Massachusetts General Hospital, and associate professor of medicine at Harvard Medical School, Boston, MA, USA. She was chair of The Infectious Disease Community of Practice of The American Society of Transplantation (2012–2018). read more

From 2007 to 2013, Dr Kotton was the president of The Transplant Infectious Disease Section of The Transplantation Society. Highlights of her time as president include the development of international guidelines on CMV management after solid organ transplant, published in Transplantation (2010, 2013, 2018). She is the first transplant infectious disease specialist to be a councillor of The Transplantation Society (2020). 

Dr Kotton has authored the past three versions of the American Society of Transplantation Travel Medicine guidelines, and has been an author of the CDC Yellow Book Chapter on Immunocompromised Hosts and Travel for the past decade. Her clinical interests include vaccinations in transplant candidates and recipients, cytomegalovirus, zoonoses, and travel and tropical medicine in the transplant setting. She is a member of the CDC Advisory Committee on Immunization Practices (ACIP) and is involved in national decisions regarding COVID-19 vaccines.

Dr Camille Kotton discloses: Consulting fees from Biotest, Evrys, ExeVir, Hookipa, Merck, Oxford Immunotec and Takeda.

 
Dr Raymund Razonable
Mayo Clinic, Rochester, MN, USA
Treatment options for refractory/resistant cytomegalovirus in solid organ transplant recipients

Dr Razonable provides his perspectives on current treatment options for refractory and resistant CMV infection in solid organ transplant recipients

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In this interview, Dr Raymund Razonable answers the following questions:

  • What are the data to support the use of maribavir in solid organ transplant recipients in clinical practice?
  • How should foscarnet be used in solid organ transplant recipients and what special considerations should clinicians have regarding resistance to this therapy?
  • Does letermovir have a role in the treatment of refractory/resistant CMV in solid organ transplant recipients?
  • Can CMV-specific hyperimmunoglobulin be used as an off-label treatment option in solid organ transplant recipients?

Raymund R Razonable, MD, is professor of medicine and a distinguished clinician at the Mayo Clinic College of Medicine and Science in Rochester, MN, USA. He serves as vice chair of the Division of Public Health, Infectious Diseases and Occupational Medicine, and program director of the Infectious Diseases Fellowship Training Programs at the Mayo Clinic. read more

Dr Razonable’s clinical, educational and research interests focus on infections related to organ transplantation, including cytomegalovirus infections. He has authored over 270 peer-reviewed original and review articles, more than 30 book chapters and over 200 abstracts on these topics.

Dr Raymund Razonable discloses: Advisory board or panel fees from GlaxoSmithKline, Merck and Roche. Grants/research support from Gilead, Regeneron and Roche.

 
Dr Genovefa Papanicolaou
Memorial Sloan Kettering Cancer Center, New York, NY, USA
Best practice in the management of refractory/resistant CMV

Dr Papanicolaou considers best practice in the management of refractory and resistant CMV in solid organ transplant recipients, based on an example patient case

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In this interview, Dr Papanicolaou answers the following questions:

  • How should testing be conducted for treatment-resistant CMV genotypes?
  • What are the treatment options for solid organ transplant recipients with refractory/resistant CMV?
  • What practical aspects should clinicians consider in patients with mutated disease?
  • What factors should be considered when personalizing treatment for CMV infection in solid organ transplant recipients?

Dr Papanicolaou is the director of clinical trials in the Infectious Disease Service at Memorial Sloan Kettering Cancer Center and professor at Weill Cornell Medical College of Cornell University, NY, USA. DrPapanicolaou, is the current chair of the Infectious Disease special Interest Group (ID-SIG) of the American Society for Transplantation and Cellular Therapy (ASTCT). read more

Dr Papanicolaou’s research focuses on viral infections after stem cell transplantation and particularly cytomegalovirus (CMV). Her areas of interest are novel therapeutics, biomarkers and personalized infection management.

Genovefa Papanicolaou discloses Advisory board or panel fees from AlloVir, Amplyx, Octapharma and Vera. Consultancy fees from Astellas, Behring, Cidara, Merck & Co, Merck Sharp & Dohme, Octapharma, Partners RX, SymBio and Takeda. Grants/research support from Merck & Co and Takeda.

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Learning Objectives & Overview
Overview

In this activity, US-based experts discuss management challenges in solid organ transplant recipients with cytomegalovirus (CMV), the evolving antiviral options for refractory and resistant CMV, and best practice for the management of refractory/resistant CMV in these patients.

This activity is jointly provided by USF Health and touchIME. read more

Target Audience

This activity has been designed to meet the educational needs of infectious disease specialists, pulmonologists, gastroenterologists, transplant specialists involved in the management CMV infection in solid organ transplant recipients.

Disclosures

USF Health adheres to the Standards for Integrity and Independence in Accredited Continuing Education. All individuals in a position to influence content have disclosed to USF Health any financial relationship with an ineligible organization. USF Health has reviewed and mitigated all relevant financial relationships related to the content of the activity.  The relevant relationships are listed below. All individuals not listed have no relevant financial relationships.

Faculty

Dr Camille Kotton discloses: Consulting fees from Biotest, Evrys, ExeVir, Hookipa, Merck, Oxford Immunotec and Takeda.

Dr Raymund Razonable discloses: Advisory board or panel fees from GlaxoSmithKline, Merck and Roche. Grants/research support from Gilead, Regeneron and Roche.

Genovefa Papanicolaou discloses Advisory board or panel fees from AlloVir, Amplyx, Octapharma and Vera. Consultancy fees from Astellas, Behring, Cidara, Merck & Co, Merck Sharp & Dohme, Octapharma, Partners RX, SymBio and Takeda. Grants/research support from Merck & Co and Takeda.

Content reviewer

Sally Alrabaa, MD has no financial interests/relationships or affiliations in relation to this activity.

Touch Medical Director

Anne Nunn has no financial interests/relationships or affiliations in relation to this activity.

USF Health Office of Continuing Professional Development and touchIME staff have no financial interests/relationships or affiliations in relation to this activity.

Requirements for Successful Completion

In order to receive credit for this activity, participants must review the content and complete the post-test and evaluation form. Statements of credit are awarded upon successful completion of the post-test and evaluation form.

If you have questions regarding credit please contact cpdsupport@usf.edu.

Accreditations

Physicians

This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through a joint providership of USF Health and touchIME. USF Health is accredited by the ACCME to provide continuing medical education for physicians.

USF Health designates this enduring material for a maximum of 0.75 AMA PRA Category 1 CreditTM.  Physicians should claim only the credit commensurate with the extent of their participation in the activity.

The European Union of Medical Specialists (UEMS) – European Accreditation Council for Continuing Medical Education (EACCME) has an agreement of mutual recognition of continuing medical education (CME) credit with the American Medical Association (AMA). European physicians interested in converting AMA PRA Category 1 CreditTM into European CME credit (ECMEC) should contact the UEMS (www.uems.eu).

Advanced Practice Providers

Physician Assistants may claim a maximum of 0.75 Category 1 credits for completing this activity. NCCPA accepts AMA PRA Category 1 CreditTM from organizations accredited by ACCME or a recognized state medical society.

The AANPCP accepts certificates of participation for educational activities approved for AMA PRA Category 1 CreditTM by ACCME-accredited providers. APRNs who participate will receive a certificate of completion commensurate with the extent of their participation.

Date of original release: 5 September 2022. Date credits expire: 5 September 2023.

If you have any questions regarding credit please contact cpdsupport@usf.edu.

Learning Objectives

After watching this activity, participants should be better able to:

  • Explain the unmet needs of solid organ transplant recipients susceptible to cytomegalovirus (CMV)
  • Discuss evolving antiviral options for solid organ transplant recipients with resistant or refractory (R/R) CMV
  • Summarize best practice for the management of R/R CMV in solid organ transplant recipients
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Question 1/5
When treating your patient who has recently received a solid organ transplant, which of the following factors would you consider to be the highest risk for CMV infection?

CMV, cytomegalovirus; HLA, human leucocyte antigen.
Correct

Donor positive/recipient negative (D+/R-) CMV status is the highest risk factor for developing CMV infection following solid organ transplant. Intense immunosuppression, HLA mismatch and severe lymphopenia are other factors that will influence potential CMV infection, but at a lower risk.

Abbreviations

CMV, cytomegalovirus; HLA, human leucocyte antigen.

Reference

Azevedo LS, et al. Clinics (Sao Paulo). 2015;70:515–23.

Question 2/5
In patients initially treated with ganciclovir, UL97 kinase gene mutations appear first in approximately what percentage of patients with CMV infection following solid organ transplant?

CMV, cytomegalovirus.
Correct

In patients initially treated with ganciclovir, UL97 kinase gene mutations appear first in about 90% of cases.

Reference

Kotton CN, et al. Transplantation. 2018;102:900–31.

Question 3/5
A retrospective review of foscarnet treatment for ganciclovir-resistant/refractory CMV infection reported which of the following?

CMV, cytomegalovirus.
Correct

The retrospective review reported virologic failure in 33% patients. Renal dysfunction by end of treatment and relapse in viraemia occurred in 51% and 31% of patients, respectively. The mortality rate was 31%.

Reference

Avery RK, et al. Transplantation. 2016;100:e74–80.

Question 4/5
Which of the following adverse events would you consider monitoring for when using maribavir in your patient with resistant/refractory CMV infection following a solid organ transplant?

CMV, cytomegalovirus.
Correct

A phase III study of maribavir vs investigator-assigned therapy reported dysgeusia in 37.2% of patients. There were no reports of thrombosis, transfusion-related acute lung injury or Fanconi syndrome.

Reference

Avery RK, et al. Clin Infect Dis. 2021;doi:10.1093/cid/ciab988.

Question 5/5
Which of the following monitoring regimens would you implement when using ganciclovir in your patient with resistant/refractory CMV infection following a solid organ transplant?

CMV, cytomegalovirus.
Correct

For patients treated with ganciclovir, it is recommended to monitor complete blood count differential, serum creatinine and serum electrolytes. The aim is to allow the adjustment of ganciclovir dose based on renal function and to be able to switch to another agent or strategy if renal function continues to worsen.

Reference

El Helou G, Razonable RR. Expert Opin Drug Saf. 2019;18:1017–30.

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