medwireNews: Adding lomustine to standard chemotherapy with idarubicin and cytarabine significantly improves survival in fit older patients with favorable- or intermediate-risk acute myeloid leukemia (AML), phase III trial data show.
Toxicity was higher with lomustine but “remained acceptable and manageable in the context of a therapy involving an alkylating agent,” Arnaud Pigneux (Bordeaux University Hospital, France) and co-authors note.
They add that the findings “validate the addition of lomustine to our standard of care.”
The LAM-SA 2007 open-label study included 424 individuals aged 60 years or older with previously untreated AML. To be included in the trial, the patients had to be fit (ECOG performance status and Sorror scores below 3) and not have unfavorable cytogenetics.
The study participants were randomly assigned to receive induction therapy with idarubicin and cytarabine with or without lomustine. Those who had a complete response (CR) or CR with incomplete recovery (CRi) following induction therapy subsequently received consolidation therapy with their assigned treatment.
The researchers report in the Journal of Clinical Oncology that the rate of CR or CRi was significantly higher among patients who received lomustine compared with those who did not, at 84.7% of 209 versus 74.9% of 215.
When analyzing the data for the primary outcome of overall survival (OS), the team found that the treatment effect changed over time. They therefore considered the induction and consolidation periods separately.
During induction, there was no significant difference in OS between the patients who did and did not receive lomustine (3.7 vs 7.7%).
By contrast, the 2-year OS rate was significantly higher among the patients who received the alkylating agent compared with those who did not, at 56% versus 48% and a hazard ratio of 0.73.
In addition, event-free survival rate for the whole duration of the trial was significantly higher with lomustine than without it (41.0 vs 26.0%), while the cumulative incidence of relapse was significantly lower (40.2 vs 60.3%).
Patients who received lomustine experienced thrombocytopenia for 3–7 days more and neutropenia for 2–5 days more than those who did not receive lomustine, and they had a higher rate of general toxicity (at least one grade 3–4 event; 62 vs 52%), but there was no significant difference between the two groups in the 2-year cumulative incidence of toxicity-related deaths (12.4 vs 7.4%).
In an accompanying editorial, Hetty Carraway, from the Cleveland Clinic in Ohio, USA, says that it is ”commendable” that the study authors focused on patients most likely to benefit from enhanced chemotherapy based on their previous work.
In future “proper selection of this population of patients for [idarubicin, cytarabine, and lomustine] therapy will be important to ensure they have the appropriate risk:benefit ratio,” Carraway remarks.
She adds: “This is a persistent issue for all of our older patients with AML, whether they are candidates for lomustine therapy or not.”
By Laura Cowen
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