SAL-DaunoDouble Trial Interim Analysis: Single versus Double Induction with 7+3 for Patients with Newly Diagnosed AML

2020 Year in Review - AML

Data are lacking on the value of a second induction cycle in patients with acute myeloid leukemia (AML) with a good early response at day 15 after first induction with 7 days of cytarabine plus 3 days of anthracycline (7+3). Interim results are available from the German Study Alliance Leukemia (SAL)-DaunoDouble trial, which prospectively assessed the outcome of patients with a good early response according to the number of induction cycles. Noninferiority of single versus double induction was assumed if the rate of complete remission (CR)/CR with incomplete hematologic recovery (CRi) was within a margin of 7.5%.

Newly diagnosed patients with AML, aged 18 to 65 years, received a first induction cycle with 7 days of cytarabine plus 3 days of daunorubicin (7+3). A blast count <5% on day 15 after the initiation of chemotherapy was defined as good response. Patients with good response were then randomized to a second induction cycle (arm D [double]) versus no additional induction (arm S [single]). The primary end point was CR/CRi rate after induction; secondary end points were recurrence-free survival (RFS) and overall survival (OS).

A total of 624 patients were enrolled and received a first 7+3 induction cycle between 2014 and 2020. Of these patients, 270 (43%) achieved a marrow blast clearance (blasts <5%) on day 15 and were randomized to arm S (n = 133) or arm D (n = 137). The median age was 52 years, and NPM1 and FLT3–internal tandem duplication mutations were present in 53.2% and 24% of patients, respectively. Favorable, intermediate, and adverse European LeukemiaNet risk was observed among 55.1%, 35%, and 9.9% of patients, respectively. A total of 86% and 85.1% of patients achieved CR/CRi after single and double induction, respectively. For 224 predefined per-protocol patients, the CR/CRi rates were 88.2% versus 91.4% (95% confidence interval, –4.7-11.1; P value for noninferiority = .145) for single and double induction, respectively. The 3-year RFS was lower following single induction versus double induction after a median follow-up of 24 months (53% vs 63%; P = .12). Landmark 3-year OS rates were similar with single versus double induction (74% vs 75%; P = .64). Adverse events were similar between arms, occurring in 97.7% and 97.1% of patients for the single- and double-induction arms, respectively. Febrile neutropenia occurred in 13.5% of patients in the single-induction arm and 15.3% of patients in the double arm.

The interim analysis of the SAL-DaunoDouble trial suggests that single induction with a 7+3 regimen of cytarabine plus anthracycline in patients with AML with a good early response at day 15 may be noninferior to double induction, although the results were not statistically significant for this comparison.

Rollig C, Steffen B, Alakel N, et al. Remission and Survival after Single Versus Double Induction with 7+3 for Newly Diagnosed Acute Myeloid Leukemia: Results from the Planned Interim Analysis of Randomized Controlled SAL-DaunoDouble Trial. Presented at: 62nd American Society of Hematology Annual Meeting & Exposition, December 5-8, 2020. Abstract 458.

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