194 - Combinatorial Polyfunctionality Analysis of Antigen-specific T-cell Subsets (COMPASS) as a Predictor for Clinically Significant CMV Infection in the Letermovir Era

Background: Increased CMV reactivation is observed following discontinuation of letermovir prophylaxis after hematopoietic cellular transplantation (HCT) and decreased CMV-specific polyfunctional T-cell immunity has been proposed as a possible mechanism (BBMT 2020;26:S68). COMPASS is a novel analytical tool that integrates polyfunctional T-cell cytokine responses into a single score value (Nat Biotechnol 2015;33:610). We employed COMPASS for the first time in the HCT setting to determine if CMV-specific immunodeficiency is associated with late CMV events in a prospective cohort of allogeneic HCT recipients receiving either letermovir or preemptive therapy.

Methods: Peripheral blood mononuclear cells were collected 3 months post-HCT and assessed with a 13-color intracellular cytokine staining (ICS) assay that includes 5 functional markers. Intermediate early-1 (IE-1) antigen and phosphoprotein 65 (pp65) were used to stimulate polyfunctional T-cell responses that were defined using COMPASS generated polyfunctionality scores (PFS). CMV DNAemia was monitored by weekly plasma PCR and patients who reactivated were treated with preemptive therapy per institutional standards. Cumulative incidence of clinically significant CMV infection (cs-CMV; ≥500 IU/mL or CMV disease) by day 270 was assessed. Univariable and multivariable Cox regression were used to estimate the association of polyfunctional T-cell responses (upper quartile versus lower 3 quartiles) with cs-CMV infection by day 270 post-HCT.

Results: 56 letermovir recipients and 93 preemptive controls were evaluated. Time to first clinically significant CMV (cs-CMV) infection after HCT and among day 100 survivors in both groups is shown in Figure 1. COMPASS PFS at 3 months were significantly lower in letermovir recipients (Figure 2). After adjusting for CMV infection before day 100, CD4 and CD8 PFS to IE-1 and pp65 below the upper quartile were associated with higher risk of late cs-CMV infection, with IE-1 CD8 PFS reaching statistical significance (Figure 3).Figure 1
Figure 2
Figure 3


Conclusion: Our findings demonstrate that COMPASS is a valuable tool to evaluate multiple, T-cell cytokine responses to CMV in HCT recipients.  COMPASS appears to be useful to identify patients at risk for late cs-CMV infection.

Presenting Author(s)

• 

  Danniel Zamora, MD

  Infectious Diseases Acting Instructor
  University of Washington
  Seattle, Washington

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.

  Slides Slides and Audio

Co-Author(s)

• ED

  Elizabeth Duke, MD

  Acting Assistant Professor
  Fred Hutch
  Seattle, Washington

  Disclosure: Merck (Grant/Research Support)
• HX

  Hu Xie, MS

  Statistical Research Associate
  Fred Hutchinson Cancer Research Center; University of Washington
  Seattle, Washington

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
• BE

  Bradley Edmison, BS

  Research Technician
  Fred Hutchinson Cancer Research Center
  Seattle, Washington

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
• BA

  Brenda Akoto, n/a

  Research Technician
  Fred Hutch
  Seattle, Washington

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
• RK

  Richard Kiener, PhD

  Researcher
  University of Regensberg
  Regensberg, Bayern, Germany

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
• TS

  Terry Stevens-Ayers, MSc

  Research Technician
  Fred Hutchinson Cancer Research Center; University of Washington
  Seattle, Washington

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
• RW

  Ralf Wagner, PhD

  Professor
  University of Regensberg
  Regensberg, Bayern, Germany

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
• MM

  Marco Mielcarek, MD

  Professor
  Fred Hutchinson Cancer Research Center; University of Washington
  Seattle, Washington

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
• JS

  Joshua Schiffer, MD, MSc

  Associate Professor
  Fred Hutch
  Seattle, Washington

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
• SD

  Stephen De Rosa, MD

  Associate Member
  Fred Hutch
  Seattle, Washington

  Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
• 

  Michael Boeckh, MD PhD

  Member
  Fred Hutchinson Cancer Research Center
  Seattle, Washington

  Disclosure: AlloVir (Consultant)EvrysBio (Advisor or Review Panel member, Other Financial or Material Support, share options)Gilead (Consultant, Grant/Research Support)GSK (Consultant)Helocyte (Advisor or Review Panel member, Shareholder)Lophius (Grant/Research Support)Merck (Consultant, Grant/Research Support)SymBio (Consultant)VirBio (Consultant, Grant/Research Support)