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

2020 Year in Review - AML - Leukemia

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.

Reference
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.

Related Items
Tibsovo Received a New Indication, in Combination with Azacitidine, for Newly Diagnosed Patients with AML and IDH1 Mutation
JHOP - June 2022 Vol 12, No 3 published on June 16, 2022 in FDA Oncology Update, Leukemia
Vidaza Received New Indication for Patients with Newly Diagnosed Juvenile Myelomonocytic Leukemia
JHOP - June 2022 Vol 12, No 3 published on June 16, 2022 in FDA Oncology Update, Leukemia, Pediatric Cancer
Arsenic Trioxide–Induced QTc Interval Prolongation and the Potential Benefit of Beta-Blockers in Patients with Acute Promyelocytic Leukemia: Case Series
JHOP - April 2022 Vol 12, No 2 published on May 3, 2022 in Case Reports, Leukemia, Adverse Events
Effect of Concomitant Azole Antifungals on Duration of Myelosuppression in Newly Diagnosed Patients with AML Receiving Venetoclax in Combination with Cladribine and Low-Dose Cytarabine
JHOP - March 2022 Vol 12 Special Feature published on March 22, 2022 in HOPA Abstracts, Leukemia
Dasatinib-Induced Gynecomastia in 2 Patients with Chronic Myeloid Leukemia: Case Reports and Review of the Literature
Jessie Signorelli, PharmD, BCOP, Amir T. Fathi, MD, Gabriela Hobbs, MD
JHOP - February 2022 Vol 12, No 1 published on March 1, 2022 in Case Reports, Leukemia, Adverse Events
Lidocaine plus Tetracaine–Medicated Patch Used for Propofol Sedation During Lumbar Punctures in Pediatric Patients with Blood Cancer
Lisa R. Garavaglia, PharmD , Frank Casey, MD, Lesley Cottrell, PhD, Claudiu Faraon-Pogaceanu, MD, Stephan Paul, MD, Melvin Lee Wright, DO
JHOP - February 2022 Vol 12, No 1 published on March 1, 2022 in Original Article, Pediatric Cancer, Leukemia, Lymphoma
Myeloablative and Reduced-Intensity Preparative Regimens for Allogeneic Transplant in the Outpatient versus Inpatient Setting in Patients with Acute Myeloid Leukemia or Myelodysplastic Syndromes
Gretchen Pardo, PharmD, Beth Eddy, PharmD, BCOP, Zahra Mahmoudjafari, PharmD, BCOP, Dennis Grauer, PhD, MS, Joseph McGuirk, DO
JHOP - August 2021 Vol 11, No 4 published on August 17, 2021 in Original Article, Transplant, Leukemia, Myelodysplastic Syndromes, Conditioning Regimen
Pharmacy Resident–Led Medication Reconciliation and Patient Education Service in Adults with Leukemia Receiving Anticancer Oral Agents: A Pilot Study
Lily Y. Jia, PharmD, BCOP, Jessie Signorelli, PharmD, BCOP, Samantha O. Luk, PharmD, BCOP, E. Bridget Kim, PharmD, BCPS, BCOP, Gayle C. Blouin, PharmD, BCOP
JHOP - June 2021 Vol 11, No 3 published on June 16, 2021 in Original Article, Leukemia, Oncology Pharmacy Programs
Pegaspargase-Induced Diabetic Ketoacidosis in a Patient with Acute Lymphoblastic Leukemia
Ellen Madarang, PharmD, BCOP, Leslie Gallardo, PharmD, BCPS, Terrence Bradley, MD
JHOP - June 2021 Vol 11, No 3 published on June 16, 2021 in Case Reports, Acute Lymphoblastic Leukemia, Leukemia, Adverse Events
Oral Azacitidine Prolongs Survival in Patients with Acute Myeloid Leukemia
Robert J. Ignoffo, PharmD, FASHP, FCSHP, FHOPA
JHOP - April 2021 Vol 11, No 2 published on April 27, 2021 in From the Literature, Leukemia
© Amplity Health. All rights reserved.

Subscribe Today!

To sign up for our newsletter or print publications, please enter your contact information below.

I'd like to receive: