Gemtuzumab ozogamicin in children with relapsed or refractory acute myeloid leukemia: a report by Berlin-Frankfurt-Münster study group

Abstract

Despite intensified salvage treatments, children with relapsed/refractory acute myeloid leukemia have poor survival. We evaluated Gemtuzumab Ozogamicin (CD33-targeted drug) used on compassionate basis in patients diagnosed from 1995 until 2014 within Acute Myeloid Leukemia-Berlin-Frankfurt-Munster studies and identified 76 patients (<18 years) with highly-advanced and pretreated acute myeloid leukemia [refractory de novo acute myeloid leukemia (n=10), de novo acute myeloid leukemia refractory to relapse (1st early: n=41; 1st late: n=10; 2nd or more: n=10), and secondary acute myeloid leukemia (n=5)]. At doses of 2.5-10 mg/m,, Gemtuzumab Ozogamicin was administered in 1-4 cycles as single agent (47%), combined with cytarabine (47%), or others (6%). Most common grade 3/4 adverse events were infections or febrile neutropenia (78% of severe adverse events), infusion-related immunologic reactions (6%), and gastrointestinal symptoms (5%). Three patients experienced veno-occlusive disease (one fatal due to exacerbation of a preexisting cardiomyopathy). Sixty-four percent received subsequent hematopoietic stem cell transplantation. Probability of 4-year overall survival was 18±5% in all, 27±7% in patients with and 0% in patients without hematopoietic stem cell transplantation (p<0.0001). Administration of Gemtuzumab Ozogamicin on a patient-specific, compassionate use basis was frequently considered in our study group and proved to be effective for bridging children with very advanced AML to hematopoietic stem cell transplantation. Uniform prospective studies for these patients are urgently needed.

Pediatric relapsed acute myeloid leukemia: a systematic review

“…However, conclusions cannot easily be drawn, since SCT is mostly performed in children achieving CR2 and in relatively good state [25,26]. However, we suggest, in accordance with previous studies [23,27,28], that allo-SCT in CR2 is resulting in better long-term clinical outcome than chemotherapy only, acknowledging that several studies have reported a few survivors with the latter approach. This difference may be due to the limited 2-year OS-rate reported, and thus, in comparison with 5-and 10-year OS-rates, result in biased outcome in favor of chemotherapy only.…”

“…After relapse, the majority of children was treated with an SCT. Outcome seemed better in these patients compared to chemotherapy only, with OS-rates comparable to other recent studies [23,24]. However, conclusions cannot easily be drawn, since SCT is mostly performed in children achieving CR2 and in relatively good state [25,26].…”

Acute Myeloid Leukemia in Children: Emerging Paradigms in Genetics and New Approaches to Therapy

“…More recent studies have demonstrated that lower doses of GO can produce similar outcomes with less treatment-related mortality, leading to re-approval of GO in adult AML therapy [ 49 , 50 ]. GO was subsequently incorporated into pediatric clinical trials in both relapsed and upfront therapies where it improved EFS and reduced relapse risk; however, OS and CR rates remained unchanged [ 14 , 51 ]. The reduced relapse risk (32.8% vs. 41.3%) when GO was given in upfront therapy in COG AAML0531 was offset by increased treatment-related mortality (8.6% vs. 5.9%) [ 14 ].…”

Pediatric acute myeloid leukemias treatment: current scientific view

“…При среднем периоде наблюдения 4,3 го да ОВ в общей когорте составила 18 ± 5 %, тогда как у больных, которым проведена ТГСК после гемтузума ба озогамицина, -27 %. Больших различий в ОВ при проведении монотерапии гемтузумабом озогами цином и в комбинации с цитарабином (± винкристин) не обнаружено [83,84].…”

“…В норме обеспечивают клеточный метаболизм. Мутированные формы энзима приводят к накоплению (D) -2ги дроксиглютарата, что нарушает функционирование ряда ферментов и приводит к гиперметилированию ДНК [84]. В целом около 15 % пациентов с ОМЛ име ют мутации либо в IDH1, либо в IDH2 [85,86].…”