by Peter D. Steinberg

Despite preemptive therapy, cytomegalovirus infection (CMVi) significantly impacts outcomes and resource utilization in allogeneic haematopoietic cell transplantation (HCT) recipients, particularly among those with recurrent CMVi episodes.

In a retrospective analysis of data from 183 allogeneic HCTs from 172 recipients, 57% of patients who suffered a first CMVi had two or more recurrent episodes, and 20% had four or more recurrences.

The study was presented by Prof. Rafael F. Duarte at the 44th Annual Meeting of the European Society for Blood and Marrow Transplantation (EBMT) in Lisbon, Portugal.

Compared to matched related HCT recipients, ≥2 CMVi recurrences were more frequent in high-risk groups such as cord-blood and haploidentical recipients (hazard ratio [HR] 2.38; 95% confidence interval [CI] 1.61-3.52; p<0.001) and individuals with acute graft-versus-host disease (GVHD; HR 2.3; 95% CI 1.62-3.26; p<0.001); ≥2 recurrences were also associated with age at the time of HCT ( 1.6 per year OR HR 1.02 [1.016]; 95% CI 1-1.03; p=0.024).

In the first year post-HCT, hospital length of stay was >30 days longer in patients with CMVi than in those without; this increase was >40 additional days in patients with ≥2 recurrent CMVi, significantly longer than those with only one CMVi episode (19 days; p < 0.001).

In terms of treatment, 73.7% of CMV reactivations responded to first-line therapy, 60% to second-line, and only 30% to third-line.

The rate of adverse effects with preemptive therapy was 31% after the first line of treatment, and increased with usual drug therapy to 60% after second-line therapy.

“Given their substantial impact on outcomes and length of stay in HCT recipients, recurrent CMV infections may require sustained prophylaxis, although no clinical trial or large registry study has evaluated this strategy in patients experiencing two or more episodes,” said Prof. Duarte, who is affiliated with Hospital Universitario Puerta de Hierro in Madrid, Spain.

“Future studies will need to address the impact of two or more CMV infections, as well as the role of antibiotic prophylaxis in patients experiencing two or more recurrences.”

In a separate EBMT presentation, prophylactic therapy with the antiviral agent letermovir was found to be cost-effective at commonly accepted incremental cost-effectiveness ratio (ICER) thresholds.

The results, presented by Chloe Brown and colleagues from MSD UK and Merck & Co., Inc., were derived from a decision-analytic model evaluating total costs and lifetime QALYs from the perspective of the National Health Service and social work in Scotland, based on cost, CMV disease, and outcomes data from published sources and on general mortality risk data from the life tables for Scotland (2014-16).

Compared to standard of care, treatment with letermovir was associated with a reduced number of CMVi requiring preemptive treatment (20% vs. 49.3%), lower all-cause mortality (10.2% vs. 15.9%), increased life-years ( 0.46) and quality-adjusted life years (QALYs; 0.41), and total per-patient costs up to week 24 post-HCT; those findings resulted in an ICER of ₤12.659 per QALY gained.

Results of a probabilistic sensitivity analysis indicated that letermovir was cost-effective in 77.4% of iterations at ₤20,000 per QALY gained and 87.6% of iterations at ₤30,000 per QALY gained.

The researchers identified the reduction in mortality, increasing the age of patients treated with letermovir, and an increase in the cost of letermovir prophylaxis as the most impactful model inputs.

In January 2018, the European Medicines Agency approved letermovir to prevent CMV from becoming active and causing disease in adults receiving an allogeneic haematopoietic stem cell transplant.

Many people have CMV in their body but it is usually inactive and it does not cause harm unless the immune system is weakened.

“I predict implementation of prophylaxis as a strategy to treat CMV infection in allogeneic HCT will be quicker than the paradigm shift from treatment to prophylaxis in antifungal management,” Prof. Duarte commented.

“In fact, the shift is already happening in CMV management, as indicated by the increasing number of studies exploring the impact of the current CMV paradigm in many centres. This trend will accelerate as letermovir becomes more widely available.”

Source: Ritz Communications