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Addition of gemtuzumab ozogamicin to frontline 7+3: A case report

Sep 18, 2020

During the 2nd How to Diagnose and Treat Acute Leukaemia conference of the European School of Haematology (ESH), Juliette Lambert delivered an oral presentation on the addition of gemtuzumab ozogamicin (GO) to frontline cytarabine plus the anthracycline, daunorubicin (7+3) for the treatment of acute myeloid leukemia (AML), with a focus on a case report.1 This is the second in a series of case reports about the addition of a third agent to frontline 7+3.

Patient details1

  • 51-year old female.
  • Past medical history: depression, gastroesophageal reflux, high blood pressure, repetitive otitis, and deep vein thrombosis in the leg.
  • Presentation: spontaneous hematomas, edema of the leg, tinnitus, shortness of breath, and fatigue.
  • Laboratory results (Table 1) showed anemia, thrombocytopenia, neutropenia, 16% circulating blasts, and a low prothrombin time, with low factor V.
    • Liver and renal function were normal.
  • Bone marrow aspirate: 25% blasts, 34% monocytes.
  • Cytogenetics:
    • Normal karyotype
    • NMP1 mutation
    • FLT3-ITD mutation
  • Additional investigations:
    • Cardiac ultrasound: 68% left ventricular ejection fraction
    • Chest X-ray: Normal

Table 1. Laboratory results at presentation1

PMN, polymorphonuclear leukocyte; WBC, white blood cell.



Normal range

Hemoglobin, g/dL



Platelets, × 109/L



WBCs, × 109/L



PMNs, × 109/L



Circulating blasts, %


Prothrombin time, %



Factor V, %



Fibrinogen, g/L



Fibrinogen and fibrin degradation products



AML with NPM1 mutation and FLT3-ITD mutation.

Management plan

The patient was included in the ALFA 0701 trial.


  • Daunorubicin (60 mg/m2 on Days 1–3)
  • Cytarabine (200 mg/m2 on Days 1–7)
  • GO (3 mg/m2 on Days 1, 4, and 7)
  • During aplasia, the patient developed:
    • cutaneous rash related to cytarabine,
    • hemorrhagic syndrome with purpura of the lower limbs, spontaneous hematomas, and retinal hemorrhage,
    • febrile neutropenia, treated with broad spectrum antibiotics (piperacillin-tazobactam and vancomycin), and
    • colitis associated with toxigenic clostridium difficile, treated with metronidazole.

GO is a conjugate of the anti-tumor anthracycline antibiotic, calicheamicin, linked to an anti-CD33 monoclonal antibody. The CD33 antigen is expressed in the leukemic blasts of ~ 85–90% of cases, therefore GO can bind specifically to and is internalized by these cells, increasing drug efficacy.1

NPM1 and FLT3-ITD mutations are associated with high CD33 expression so these patients are likely to be better responders to GO therapy. This was demonstrated in the combined analysis of the National Cancer Research Institute (NCRI)’s AML-16 and -17 trials.1,7

The AML-17 trial previously reported on the AML hub also showed that patients with FLT3 mutations with any level of measurable residual disease have a worse prognosis after transplant, with only 17% survival at 2 years after transplant.

The approval of GO for AML was complicated and has been described previously on the AML Hub. GO was first approved by the U.S. Food and Drug Administration (FDA) in 2000 based on early clinical studies of GO monotherapy. The phase I dose escalation study in patients with relapsed/refractory AML recommended 9 mg/m2 for the phase II dose, because CD33 sites were consistently saturated (> 75%) at this dose.2  The phase II studies demonstrated a 30% overall response rate. However, increased liver toxicities and prolonged cytopenia were associated with this dose.

The interim analysis of the phase III SWOG S0106 trial, comparing GO with and without 7+3 in adults with de novo AML, led to withdrawal of GO by the FDA. The results showed no difference in compete response or overall survival (OS) and an increase in treatment-related mortalities.1

Reapproval of GO was based on the ALFA 0701 trial of 7+3 with vs without GO in treatment-naïve AML (previously reported on the AML Hub) which demonstrated an improved OS (27.5 vs 21.8 months; p = 0.16) and event-free survival (13.6 vs 8.5 months; p = 0.006). The use of fractionated doses (3 mg/m2 per day for 3 days) also reduced toxicities.

The patient recovered from all adverse events and responded to induction therapy with complete remission at Day 30 (assessed by bone marrow aspiration and blood tests).


The patient received two consolidation cycles of:

  • Daunorubicin (60 mg/m2 on Day 1)
  • Cytarabine (1 g/m2/12h on Days 1–4)
  • GO (3 mg/m2 on Day 1)

The phase III GOELAMS AML 2006IR study (NCT00860639) of GO (6 mg/m2) with vs without 7+3, in adults with de novo AML, also showed improved event-free survival for intermediate-risk patients who could not receive allogeneic hematopoietic stem cell transplantation (HSCT) (53.7% vs 27%, respectively; p = 0.03) but no difference in OS.1,3

The MRC AML15 trial of GO (3 mg/m2) with/without 7+3, in younger adults (< 60 years of age) with AML showed improved survival for patients with favorable cytogenetics (p = 0.001).1,4

The NCRI AML16 trial of GO (3 mg/m2) with vs without 7+3, in older adults (> 60 years of age) with treatment-naïve AML also showed GO significantly improved OS across all groups (25% vs 20%; p = 0.05).1,5

A meta-analysis of the ALFA-0701, SWOG S0106, GOELAMS AML2006IR, AML-15, and AML-16 studies, comprising of 3,325 patients, demonstrated that GO significantly improved OS in patients with non-adverse cytogenetics (favorable cytogenetics: 6.3% vs 55.2%, GO vs no GO; p = 0.0005; intermediate risk patients: 39.4% vs 34.1%; p = 0.007).1,6


  • Two months after the last consolidation, the patient received myeloablative conditioning chemotherapy.
  • She received allogeneic HSCT from a related donor.
  • Sinusoidal obstructive syndrome or graft-versus-host disease did not occur.

Post-transplant evolution

The patient remains in continuous remission 10 years posttransplant.


GO improves overall survival when added to front-line chemotherapy in patients with favorable and intermediate-risk cytogenetics and can be used safely before HSCT when given in fractionated doses. Although biomarkers for GO response are still unclear, CD33 expression seems to be associated with better response.    

The first article in this series describes the addition of midostaurin to frontline 7+3. Find out more information here.

  1. Lambert J. Addition of gemtuzumab ozogamicin to frontline 7+3 chemotherapy. Oral abstract. ESH 2nd How to Diagnose and Treat: Acute Leukaemia Conference. Jul 1, 2020; Virtual.
  2. Sievers EL, Appelbaum FR, Spielberger RT, et al. Selective ablation of acute myeloid leukemia using antibody-targeted chemotherapy: A phase I study of an anti-CD33 calicheamicin immunoconjugate. Blood. 1999; 93(11):3678-3684. DOI:
  3. Delaunay J, Recher C, Pigneux A, et al. Addition of gemtuzumab ozogamycin to chemotherapy improves event-free survival but not overall survival of AML patients with intermediate cytogenetics not eligible for allogeneic transplantation. Results of the GOELAMS AML 2006 IR study. Blood. 2011;118(21):79. DOI:
  4. Burnett AK, Hills RK, Milligan D, et al. Identification of patients with acute myeloblastic leukemia who benefit from the addition of gemtuzumab ozogamicin: results of the MRC AML15 trial. J Clin Oncol. 2011;29(4):369-77. DOI: 1200/JCO.2010.31.4310
  5. Burnett AK, Russell NH, Hills RK, et al. Addition of gemtuzumab ozogamicin to induction chemotherapy improves survival in older patients with acute myeloid leukemia. J Clin Oncol. 2012;30(32):3924-31. DOI: 10.1200/JCO.2012.42.2964
  6. Hills RK, Castaigne S, Appelbaum FR, et al. The addition of gemtuzumab ozogamicin to induction chemotherapy in acute myeloid leukaemia: an individual patient data meta-analysis of randomised trials in adults. Lancet Oncol. 2014;15(9):986-996. DOI: 1016/S1470-2045(14)70281-5
  7. Khan N, Hills RL, Virgo P, et al. Expression of CD33 is a predictive factor for effect of gemtuzumab ozogamicin at different doses in adult acute myeloid leukaemia. Leukemia. 2017;31(5):1059-1068. DOI: 1038/leu.2016.309.