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Background of CMV infection in HSCT

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Hematopoietic stem cell transplant (HSCT) patients are at increased risk for cytomegalovirus (CMV) infection, disease, and associated mortality1–4

Positive CMV serostatus pre-HSCT is a strong predictor of CMV infection and disease.1,2

  • CMV infection has been shown to occur in ~30-65% of CMV-seropositive allogeneic HSCT patients.3,5
  • More than 30% of HSCT patients who were CMV-seropositive or had a seropositive donor had CMV infection within 1 month post-transplant.4

Any level of CMV viremia is associated with increased risk of mortality in the first year post-HSCT4,a

CMV viral load as a time-dependent risk factor for overall mortality 1 year after HSCT (n=926)4

Overall Risk of Mortality with CMV Post-HSCT

CI, confidence interval; HR, hazard ratio.

(a) Results from a large, retrospective, noninterventional cohort study of previously collected CMV viral load and clinical outcome measures (n=926).4

Early CMV reactivation is associated with increased non-relapse mortality and reduced overall survival following allogeneic HSCT5

Overall Risk Compared to Relative Risk of No CMV Reactivation

HSCT Patient Outcomes Associated with CMV Reactivation

Adapted from a CIBMTR analysis by Teira et al.

ALL, acute lymphoblastic leukemia; AML, acute myeloid leukemia; CIBMTR, Center for International Blood and Marrow Transplant Research; CML, chronic myeloid leukemia; MDS, myelodysplastic syndrome.

Study limitations

  • No data was collected on how CMV reactivation was monitored with respect to tests used and values applied for implementing preemptive therapy.5
  • Institutional practices for preemptive and prophylactic therapy vary with respect to initiation and duration of therapy, affecting the ability to assess efficacy of initial therapy and duration of CMV reactivation.5
  • The retrospective nature of the analysis limits generalization of results across transplant settings.5

Study design

  • Retrospective, multivariate analysis of 9,469 patients from the Center for International Blood and Marrow Transplant Research (CIBMTR) database who received their first allogeneic HSCT between 2003 and 20105
  • Multivariable analysis of risk factors for outcomes depending on CMV serostatus and reactivation with hematologic disease relapse, non-relapse mortality, and overall survival (AML [n=5,310], ALL [n=1,883], CML [n=1,079], and MDS [n=1,197])5

How could initiation of CMV prophylaxis make a difference for your adult R+ patients?

References

  1. George B, Pati N, Gilroy N, et al. Pre-transplant cytomegalovirus (CMV) serostatus remains the most important determinant of CMV reactivation after allogeneic hematopoietic stem cell transplantation in the era of surveillance and preemptive therapy. Transpl Infect Dis. 2010;12(4):322–329.
  2. Ljungman P, Hakki M, Boeckh M. Cytomegalovirus in hematopoietic stem cell transplant recipients. Hematol Oncol Clin North Am. 2011;25(1):151–169.
  3. Sousa H, Boutolleau D, Ribeiro J, et al. Cytomegalovirus infection in patients who underwent allogeneic hematopoietic stem cell transplantation in Portugal: a five-year retrospective review. Biol Blood Marrow Transplant. 2014;20(12):1958–1967.
  4. Green ML, Leisenring W, Xie H, et al. Cytomegalovirus viral load and mortality after haematopoietic stem cell transplantation in the era of pre-emptive therapy: a retrospective cohort study. Lancet Haematol. 2016;3(3):e119–e127.
  5. Teira P, Battiwalla M, Ramanathan M, et al. Early cytomegalovirus reactivation remains associated with increased transplant-related mortality in the current era: a CIBMTR analysis. Blood. 2016; 127(20)2427-2438. doi:10.1182/blood-2015-11-679639

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Indications

PREVYMIS® (letermovir) is indicated for prophylaxis of cytomegalovirus (CMV) infection and disease in adult CMV-seropositive recipients [R+] of an allogeneic hematopoietic stem cell transplant (HSCT).

 

PREVYMIS® is indicated for prophylaxis of CMV disease in adult kidney transplant recipients at high risk (Donor CMV seropositive/Recipient CMV seronegative [D+/R-]).

Selected Safety Information

  • PREVYMIS is contraindicated in patients receiving pimozide or ergot alkaloids.
      • Increased pimozide concentrations may lead to QT prolongation and torsades de pointes.
      • Increased ergot alkaloids concentrations may lead to ergotism.
  • PREVYMIS is contraindicated with pitavastatin and simvastatin when co-administered with cyclosporine. Significantly increased pitavastatin or simvastatin concentrations may lead to myopathy or rhabdomyolysis.
  • The concomitant use of PREVYMIS and certain drugs may result in potentially significant drug interactions, some of which may lead to adverse reactions (PREVYMIS or concomitant drugs) or reduced therapeutic effect of PREVYMIS or the concomitant drug.
  • Intravenous formulation of PREVYMIS contains the excipient hydroxypropyl betadex. PREVYMIS injection should be used only in patients unable to take oral therapy and patients should be switched to oral PREVYMIS as soon as they are able to take oral medications. If possible, intravenous administration should not exceed 4 weeks.
  • In patients with renal impairment, accumulation of hydroxypropyl betadex may occur. In adult patients with CLcr less than 50 mL/min and in pediatric patients with a similar degree of renal impairment (based on age-appropriate assessment of renal function) receiving PREVYMIS injection, closely monitor serum creatinine levels.
  • Animal studies have shown the potential for hydroxypropyl betadex to cause ototoxicity. The active ingredient, letermovir, is not known to be associated with ototoxicity.
  • The rate of adverse events occurring in at least 10% of adult HSCT recipients treated with PREVYMIS and at a frequency at least 2% greater than placebo were nausea (27% vs 23%), diarrhea (26% vs 24%), vomiting (19% vs 14%), peripheral edema (14% vs 9%), cough (14% vs 10%), headache (14% vs 9%), fatigue (13% vs 11%), and abdominal pain (12% vs 9%).
  • Hypersensitivity reaction, with associated moderate dyspnea, occurred in one adult HSCT recipient following the first infusion of IV PREVYMIS after switching from oral PREVYMIS, leading to treatment discontinuation.
  • The most common adverse event occurring in at least 10% of adult kidney transplant recipients treated with PREVYMIS and at a frequency greater than valganciclovir was diarrhea (32% vs 29%).
  • If PREVYMIS is co-administered with cyclosporine, the dosage of PREVYMIS should be decreased to 240 mg once daily.
  • Co-administration of PREVYMIS may alter the plasma concentrations of other drugs and other drugs may alter the plasma concentrations of PREVYMIS. Consult the full Prescribing Information prior to and during treatment for potential drug interactions.
  • Closely monitor serum creatinine levels in patients with CLcr less than 50 mL/min using PREVYMIS injection.
  • PREVYMIS is not recommended for patients with severe (Child-Pugh Class C) hepatic impairment.
  • For patients with creatinine clearance (CLcr) greater than 10 mL/min (by Cockcroft-Gault equation), no dosage adjustment of PREVYMIS is required based on renal impairment. The safety of PREVYMIS in patients with end-stage renal disease (CLcr less than 10 mL/min), including patients on dialysis, is unknown.

Before prescribing PREVYMIS® (letermovir), please read the accompanying Prescribing Information. The Patient Information and Instructions for Use also are available.

Indications

PREVYMIS® (letermovir) is indicated for prophylaxis of cytomegalovirus (CMV) infection and disease in adult CMV-seropositive recipients [R+] of an allogeneic hematopoietic stem cell transplant (HSCT).

 

PREVYMIS® is indicated for prophylaxis of CMV disease in adult kidney transplant recipients at high risk (Donor CMV seropositive/Recipient CMV seronegative [D+/R-]).

PREVYMIS® (letermovir) is indicated for prophylaxis of cytomegalovirus (CMV) infection and disease in adult

PREVYMIS® (letermovir) is indicated for prophylaxis of cytomegalovirus (CMV) infection and disease in adult CMV-seropositive recipients [R+] of an allogeneic hematopoietic stem cell transplant (HSCT).

PREVYMIS® is indicated for prophylaxis of CMV disease in adult kidney transplant recipients at high risk (Donor CMV seropositive/Recipient CMV seronegative [D+/R-]).

Selected Safety Information

  • PREVYMIS is contraindicated in patients receiving pimozide or ergot alkaloids.
      • Increased pimozide concentrations may lead to QT prolongation and torsades de pointes.
      • Increased ergot alkaloids concentrations may lead to ergotism.
  • PREVYMIS is contraindicated with pitavastatin and simvastatin when co-administered with cyclosporine. Significantly increased pitavastatin or simvastatin concentrations may lead to myopathy or rhabdomyolysis.
  • The concomitant use of PREVYMIS and certain drugs may result in potentially significant drug interactions, some of which may lead to adverse reactions (PREVYMIS or concomitant drugs) or reduced therapeutic effect of PREVYMIS or the concomitant drug.
  • Intravenous formulation of PREVYMIS contains the excipient hydroxypropyl betadex. PREVYMIS injection should be used only in patients unable to take oral therapy and patients should be switched to oral PREVYMIS as soon as they are able to take oral medications. If possible, intravenous administration should not exceed 4 weeks.
  • In patients with renal impairment, accumulation of hydroxypropyl betadex may occur. In adult patients with CLcr less than 50 mL/min and in pediatric patients with a similar degree of renal impairment (based on age-appropriate assessment of renal function) receiving PREVYMIS injection, closely monitor serum creatinine levels.
  • Animal studies have shown the potential for hydroxypropyl betadex to cause ototoxicity. The active ingredient, letermovir, is not known to be associated with ototoxicity.
  • The rate of adverse events occurring in at least 10% of adult HSCT recipients treated with PREVYMIS and at a frequency at least 2% greater than placebo were nausea (27% vs 23%), diarrhea (26% vs 24%), vomiting (19% vs 14%), peripheral edema (14% vs 9%), cough (14% vs 10%), headache (14% vs 9%), fatigue (13% vs 11%), and abdominal pain (12% vs 9%).
  • Hypersensitivity reaction, with associated moderate dyspnea, occurred in one adult HSCT recipient following the first infusion of IV PREVYMIS after switching from oral PREVYMIS, leading to treatment discontinuation.
  • The most common adverse event occurring in at least 10% of adult kidney transplant recipients treated with PREVYMIS and at a frequency greater than valganciclovir was diarrhea (32% vs 29%).
  • If PREVYMIS is co-administered with cyclosporine, the dosage of PREVYMIS should be decreased to 240 mg once daily.
  • Co-administration of PREVYMIS may alter the plasma concentrations of other drugs and other drugs may alter the plasma concentrations of PREVYMIS. Consult the full Prescribing Information prior to and during treatment for potential drug interactions.
  • Closely monitor serum creatinine levels in patients with CLcr less than 50 mL/min using PREVYMIS injection.
  • PREVYMIS is not recommended for patients with severe (Child-Pugh Class C) hepatic impairment.
  • For patients with creatinine clearance (CLcr) greater than 10 mL/min (by Cockcroft-Gault equation), no dosage adjustment of PREVYMIS is required based on renal impairment. The safety of PREVYMIS in patients with end-stage renal disease (CLcr less than 10 mL/min), including patients on dialysis, is unknown.

Before prescribing PREVYMIS® (letermovir), please read the accompanying Prescribing Information. The Patient Information and Instructions for Use also are available.

PREVYMIS is contraindicated in patients receiving pimozide or

  • PREVYMIS is contraindicated in patients receiving pimozide or ergot alkaloids.
    • Increased pimozide concentrations may lead to QT prolongation and torsades de pointes.