Even patients with poor-risk cytogenetics experienced benefits from norethandrolone.

Curative therapies are also possible in AML. Hematopoietic stem cell transplant has curative potential for AML, though around half of all adults have dormant CMV. CMV infection is the most common viral infection in patients after undergoing transplantation.


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Results from a phase 3 clinical trial, MK-8228-001 (NCT02137772), indicate that letermovir can protect transplant patients from CMV. Letermovir inhibits CMV by targeting the viral terminase complex to stop viral replication.

This trial enrolled 565 adult patients from 67 research centers in 20 countries and compared letermovir with placebo in the prevention of an active CMV infection after transplant with donor stem cells. The primary endpoint was clinically significant CMV infection through week 24 after transplant.

Patients underwent treatment for up to 14 weeks. Within 24 weeks of completion of treatment, 61% of patients on placebo developed active CMV infections requiring treatment or discontinued the trial.

Significantly fewer patients who received letermovir developed active infection: 38% of patients treated with letermovir developed serious CMV infection or discontinued the trial.

Adverse events were acceptable in patients receiving letermovir. Common toxicities included mild nausea, vomiting, and some swelling. The most common adverse events in the 2 arms were graft-versus-host disease (letermovir 39.1%, placebo 38.5%), diarrhea (letermovir 26.0%, placebo 24.5%), and nausea (letermovir 26.5%, placebo 23.4%).

The most frequent serious adverse events were infection (letermovir 20.6%, placebo 18.8%) graft-versus-host disease (letermovir 9.9%, placebo 10.4%) and acute kidney injury (letermovir 1.3%, placebo 4.7%).

Treatment with letermovir also correlated with a survival benefit. At 24 weeks, 15% of patients on placebo had died, and 10% of patients on letermovir had died.

Regardless of these recent advances, OS is still short for many older patients with AML.

“Many unmet needs remain in older patients with AML as overall survival is still short for many of them. We need in particular to find new drugs and new strategies to reduce the rate of relapse,” explained Dr Pigneux.

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These results support development of therapeutics that are targeted and based on individual genetic variants and that would generalize across patient-groups to maximize effectiveness in different populations.

References

  1. Pigneux A, Béné MC, Guardiola P, et al. Addition of androgens improves survival in elderly patients with acute myeloid leukemia: a GOELAMS study. J Clin Oncol. 2017;35(4):387-93. doi: 10.1200/JCO.2016.67.6213
  2. Marty FM, Ljungman PT, Chemaly RF, et al. A phase III randomized, double-blind, placebo-controlled trial of letermovir (LET) for prevention of CMV (CMV) infection in adult CMV-seropositive recipients of allogeneic hematopoietic cell transplantation (HCT). Paper presented at: 2017 BMT Tandem Meetings; February 22-26, 2017; Orlando, Florida.