Gemtuzumab ozogamicin (Mylotarg®) as single-agent treatment for frail patients 61 years of age and older with acute myeloid leukemia: final results of AML-15B, a phase 2 study of the European Organisation for Research and Treatment of Cancer and Gruppo Italiano Malattie Ematologiche dell'Adulto Leukemia Groups

Abstract

The therapeutic activity and toxicity profile of gemtuzumab ozogamicin were assessed in 40 patients 460 years of age with acute myeloid leukemia (AML) who were not considered eligible for conventional chemotherapy because of advanced age or poor performance status. The drug was administered at the dose of 9 mg/m 2 as a single 2-h i.v. infusion on days 1 and 15. Patients who achieved a complete remission (CR/CRp) were to receive a consolidation with two additional injections of the immunotoxin at the same dose. The overall CR/CRp rate was 17% (95% CI, 8-32%). The CR/CRp rate in patients 61-75 years old was 33% (6/18), and 5% (1/22) in patients older than 75 years. Induction death occurred in seven patients (17%), all aged above 75 years. Overall survival was significantly longer in patients aged 61-75 years than in older individuals (P ¼ 0.05), and in CD33 þ cases than in CD33À cases (P ¼ 0.05). We conclude that the dose/schedule of gemtuzumab ozogamicin used in this trial is too toxic in the age group over 75 years. For these patients, additional studies with reduced doses of the immunotoxin are warranted.

Fludarabine, Cytarabine and Gentuzumab Ozogamicin (FLA-GO) as Salvage Therapy and Bridge to Transplant in Adult Relapsed Acute Myeloid Leukemia (AML) Patients

“…In a study of GO single-agent for unfit elderly patients with previously untreated AML, Amadori et al confirmed this observation [29]. In our study no association between CD33 expression and clinical outcome emerged, this is in line with others' experience in which GO wasnot delivered as single agent but rather given in association with chemotherapy [30,3 1].…”

Age and acute myeloid leukemia: real world data on decision to treat and outcomes from the Swedish Acute Leukemia Registry

“…Many randomized trials, for example, from Medical Research Council, 32 European Organisation for the Research and Treatment of Cancer, 33 Cancer and Leukemia Group B Study, 34 Southwest Oncology Group, 35 ECOG, 31 and Leukemia Group of Middle Sweden (LGMS), 8 have failed to show improvement with modifications of the standard therapy. Indeed, no newer treatment options, such as gemtuzumab, 36 clofarabine, 21 tipifarnib, 22 or fludarabine combinations, 37 have provided better or even the same level of response and survival as we show here in an unselected total population given standard intensive treatment. Newer treatments are often studied in patients judged to be unfit for standard treatment, but this seems not validated comparing ages and PS distributions in those studies to ours.…”

The role of Gemtuzumab Ozogamicin in the treatment of acute myeloid leukemia patients

“…Severe liver toxicity was observed in four cases (10%), but only one of them developed a fatal VOD. The authors stated that GO at this schedule resulted too toxic in patients aging over 75 years (Amadori et al, 2005). Conversely, in another small pilot study by Nabhan et al (2004) 12 patients with AML aging over 65 years were treated with GO as first induction; among 11 valuable cases, a response rate was observed in three patients (27%) with an RFS of 7.6 months.…”

“…The most important GO associated toxicities are myelosuppression and, consequently, febrile neutropenia: infections incidence ranges from 13 to 50% in different series (Amadori et al, 2005;Larson et al, 2005). Although pluripotent progenitor cells do not express CD33, myelosuppression may be due to the CD33-positivity of more differentiated multipotent hematopoietic cells, targeted by GO.…”