Addition of lomustine to chemotherapy for older patients with acute myeloid leukemia: result from the phase III LAM-SA 2007 trial

In the September 2018 issue of the Journal of Clinical Oncology, a group of researchers from the French Innovative Leukemia Organization (FILO) reported results from the prospective, open-label, randomized, phase III LAM-SA 2007 study (NCT00590837). The LAM-SA 2007 study is assessing the impact of the addition of lomustine, an alkylating agent, to idarubicin and cytarabine during induction and also during post-remission therapy in a population of fit elderly patients with acute myeloid leukemia (AML) with non-adverse cytogenetics.

Four hundred and fifty-nine patients aged 60 years or older with de novo AML were enrolled between February 2008 and December 2011. Overall, 424 patients were randomized to receive induction therapy consisting of idarubicin (8 mg/m²/day intravenously [IV] on days 1–5) and cytarabine (100 mg/m²/day continuous IV on days 1–7) with (n = 209; arm A) or without (n = 215; arm B) lomustine (200 mg/m² orally on day 1).

After induction therapy, 338 patients achieved complete remission (CR) or CR with incomplete recovery (CRi) and received a first consolidation with idarubicin (8 mg/m² /day IV on days 1–3) and cytarabine (50 mg/m² once every 12 hours each day subcutaneously on days 1–5) with or without lomustine (80 mg orally on day 1). This was followed by six re-induction courses of reduced doses with idarubicin (8 mg/m² /day IV on day 1) and cytarabine (50 mg/m² /12 hours/day subcutaneously on days 1– 5) with or without lomustine (40 mg orally on day 1).

The primary objective of the study was overall survival (OS) at 2 years. Secondary objectives of the study included response rate, two-year event-free survival (EFS), and safety.

Key findings:

• CR rates in arm A and arm B were 78.9% and 73%, respectively
• Response rates in arm A and arm B were 84.7% and 74.9% respectively; odds ratio = 1.86 (95% CI, 1.15–3.04), P = 0.01
• Addition of lomustine did not have an impact on survival during induction, P = 0.11
• Addition of lomustine significantly improved the 2-year OS after induction: HR = 0.73 (95% CI, 0.54–0.99), P = 0.04
  • 2-years post-induction OS in arm A and B were 56% (95% CI, 49%–62%) and 48% (95% CI, 41%–55%) respectively, P = 0.04
• Cumulative incidence for relapse (CIR) at 2 years in arm A and arm B were 40.2% (95% CI, 34.6%–49.2%) and 60.3% (95% CI, 53.8%–68.9%) respectively, P = 0.003
• 2-years EFS in arm A and arm B were 41% (95% CI, 34%–47%) and 26% (95% CI, 20%–32%) respectively, P = 0.01
• Safety
  • Hematologic toxicity at both induction and consolidation was significantly higher in arm compared with arm B
  • General toxicity of at least one grade 3–4 adverse event at induction was significantly higher in arm A compared with arm B: 62% vs 52%, P = 0.04
  • There was a trend for increased induction deaths in arm A compared with arm B: 7.7% vs 3.7%, P = 0.11

In summary, the addition of “lomustine to standard chemotherapy significantly improved the outcome of elderly patients with AML.”

The researchers concluded by stating that lomustine should also be considered for the treatment schemes for elderly patients with AML. They further added that the addition of lomustine has already become part of the standard of care for fit elderly patients with AML at their organization (FILO).