General AML

ASH 2018 | Clinical outcomes of patients with acute myeloid leukemia who underwent HSCT in the phase III ALFA-0701 study

The pivotal phase III randomized ALFA-0701 study (NCT00927498) compared the safety and efficacy of induction therapy [DA] with daunorubicin (60 mg/m2 for 3 days) and cytarabine (200 mg/mfor 7 days) plus fractionated doses of gemtuzumab ozogamicin (3 mg/m2 on days 1, 4, 7; GO arm) versus DA alone (control arm) in patients aged 50–70 years with treatment-naïve acute myeloid leukemia (AML). Patients in complete remission (CR) were administered two consolidations courses of intermediate doses of cytarabine with or without one dose of gemtuzumab ozogamicin (3 mg/mon day 1, maximum dose: 5mg), according to initial randomization.1

Results from the ALFA-0701 study demonstrate that fractionated doses of gemtuzumab ozogamicin added to standard chemotherapy significantly prolongs event-free survival (EFS) in patients with previously untreated de novo AML and has an acceptable safety profile.1 In this ALFA-0701 study, of the 271 evaluable patients, 85 received hematopoietic stem cell transplantation (HSCT) at any time during the study.  A total of 32 patients (median age = 60 years; range 51–67 years) in the GO arm and 53 patients (median age = 59; range 50–69) years in the control arm underwent HSCT, respectively. In the GO arm, 17 patients received HSCT in first CR (CR1), two after induction failure, and 13 after relapse. In the control arm, 22 patients received HSCT in CR1, nine after induction failure, and 22 after relapse.2

At the 60th American Society of Hematology Annual Meeting & Exposition, Cécile Pautas from the University Hospital of Henri-Mondor, Créteil, France, presented data from a retrospective analysis on the transplant characteristics, survival and veno-occlusive disease (VOD) outcomes of the patients who underwent HSCT in the ALFA-0701 study.2

Key findings:
  • Data below are representative of outcomes in the GO and control arm, respectively
    • 3-year survival probability: 39.4% (95% CI, 21.9–56.5) vs 44.5% (95% CI, 30.5–57.6), HR = 0.97 (95% CI, 0.53–1.75), P = 0.9081
    • 3-year survival probability for patients who received HSCT in CR1: 52.9% (95% CI, 28–73) vs 45.5% (95% CI, 24.4–64.3), HR = 0.71 (95% CI, 0.29–1.74), P = 0.4529
      • Median post-transplant survival was not yet reached in the GO arm
    • 3-year survival in patients who received HSCT after relapse or induction failure: 21% (95% CI, 3.6–48.1) vs 44.3% (95% CI, 25.8–61.2), HR = 1.42 (95% CI, 0.64–3.14), P = 0.3790
    • Non-relapse mortality rate at the end of month 12: 28.7% (95% CI, 14.1–45.2) vs 21.6% (95% CI, 11.5–33.8), HR = 1.69 (95% CI, 0.74–3.87), P = 0.2103
    • Cumulative incidence of relapse at the end of month 12: 9.4% (95% CI, 2.3–22.6) vs 31.4% (95% CI, 19.1–44.4), HR = 0.60 (95% CI, 0.27–1.33), P = 0.2181
  • Three patients in the GO arm and two in the control arm (both of whom received GO as follow-up therapy) developed VOD

In summary, post-transplant outcomes observed in patients with AML treated with standard chemotherapy with and without GO were similar. In addition, “the use of GO was not associated with an excess of VOD events after HSCT.” The speaker concluded that the results of this retrospective analysis “suggest that the administration of GO as part of induction and consolidation chemotherapy for AML does not induce excess post-transplant mortality and thus does not preclude the use of transplant as consolidation treatment following induction or salvage treatment.”

  1. Lambert J. et al. Gemtuzumab ozogamicin for de novo acute myeloid leukemia: final efficacy and safety updates from the open-label, phase 3 ALFA-0701 trial. Haematologica. 2018 Aug 3. DOI: 10.3324/haematol.2018.188888. [Epub ahead of print].
  2. Pautas C. et al. Outcomes following hematopoietic stem cell transplantation in patients treated with chemotherapy with or without gemtuzumab ozogamicin for acute myeloid leukemia. 2018 Dec 1; Oral Abstract #28: 60th ASH Annual Meeting and Exposition, San Diego, CA.
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