Advances in Non-precision Therapies Improve Outcomes in AML

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Study results support development of therapeutics that are targeted and based on individual genetic variants and would generalize across patient-groups in AML.
Study results support development of therapeutics that are targeted and based on individual genetic variants and would generalize across patient-groups in AML.

Over 70% of all patients with acute myeloid leukemia (AML) are 60 years or older. Worse prognoses tend to characterize this elderly population, due to frailty and comorbidities.

Precision medicines have, however, improved outcomes in and understanding of AML, but targeted therapies are not always well-tolerated in this population.

Increased remission, improved post-induction chemotherapy, and, in cases of hematopoietic transplants, protection from active cytomegalovirus (CMV) infection could improve outcomes in this difficult-to-treat population.

Results from 2 clinical trials emphasize the importance of continuing generalized therapeutic advances in the treatment of AML. In one trial, published in the Journal of Clinical Oncology, the addition of androgens to maintenance treatment of elderly patients with AML significantly increased survival without affecting toxicity.1

In the second trial, presented at Bone Marrow Transplant Tandem Meetings, treatment with a novel agent, letermovir, targeted active CMV in patients with hematological malignancies and other disorders who received donor hematopoietic transplants.2

In the randomized, open-label phase 3 trial of the androgen norethandrolone, Treatment Outcome in Elderly Patients (NCT00700544), researchers assessed disease-free survival (DFS) by intention to treat, the primary outcome, among 330 patients 60 years or older with AML. Patients were randomly assigned to receive norethandrolone at 10 or 20 mg/day (dependent on body mass) along with chemotherapy (165 patients) or to undergo chemotherapy alone (165 patients).

About three-quarters of patients (247) achieved complete or partial remission. Improvements in outcomes were time-sensitive, occurring among patients who did not relapse in the first year. Among these patients, in the norethandrolone arm, 5-year DFS was 31.2%; in the chemotherapy alone arm, 5-year DFS was 16.2%.

EFS was 21.5% in the norethandrolone arm and 12.9% in the chemotherapy alone arm. OS was also improved in the norethandrolone arm (26.3%) vs the chemotherapy alone arm (17.2%).

There was no significant difference in the rate of grade 3 to 4 adverse events between the 2 arms. The most frequent adverse events in either arm included infections, pulmonary toxicity, gut toxicity, cardiac toxicity, neurologic toxicity, and cutaneous toxicity.

RELATED: Intense-dose Idarubicin Consolidation Prolongs LFS in AML

Improvements with norethandrolone were generalized across patients regardless of all prognostic factors. Patients with baseline leukocytes greater than 30 x 109/L were the only subgroup that did not experience improved outcomes from norethandrolone.

“We of course expected positive results for this trial,” said the study's first author Arnaud Pigneux, MD, professor in the Service d'Hématologie Clinique et Thérapie Cellulaire in Bordeaux, France. “But what we did not expect was the huge difference in DFS for patients with less than 30x10^9/L WBC [white blood cells].”

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