Efficacy of fractionated gemtuzumab ozogamicin combined with cytarabine in advanced childhood myeloid leukaemia

Abstract

Gemtuzumab ozogamicin (GO) monotherapy is reported to yield a 20-30% response rate in advanced acute myeloid leukaemia (AML). This study examined the efficacy and tolerability of GO combined with cytarabine (GOCYT) in children with refractory/relapsed CD33(+) AML. Seventeen children received GO 3 mg/m(2) on days 1, 4 and 7 plus cytarabine 100 mg/m(2)/d for 7 d on a compassionate-use basis. Seven patients then received GO-based consolidation. At the outset of GOCYT, two patients were refractory; eight patients were in refractory first relapse; six patients had relapsed after stem cell transplantation (SCT); and one patient [del(5q) therapy-related AML (t-AML)] had not yet been treated. Mean follow-up was 17 months (8-33 months). Ten responses were obtained after GOCYT induction, including complete remission (CR) or CR without complete recovery of platelets (CRp) in six patients (35%). The responses improved in three children who received GOCYT consolidation, increasing the CR + CRp rate to 53%. SCT was subsequently performed in eight responders. Grade 3-4 adverse events consisted of haematological disorders (n = 17, 100%) and documented infections (n = 5, 29%). No cases of sinusoidal obstructive syndrome occurred. Three patients were alive at the cut-off date for this analysis, all of whom had responded to GOCYT. GOCYT combination therapy yielded a high response rate (53%) and showed acceptable toxicity in heavily pretreated children with refractory/relapsed AML. These results warrant a larger prospective study.

Dose-related efficacy and toxicity of gemtuzumab ozogamicin in pediatric acute myeloid leukemia

“…GO is occasionally combined with other chemotherapeutics, such as fludarabine, anthracyclines, cyclophosphamide, busulfan and cytarabine [22,23,30]. When single dose of GO as part of combination therapy increases, incidence of VOD does not change significantly (r 2 = 0.023, p = 0.675) (Figure 4) also not for total dose of gemtuzumab (r 2 = 0.159, p = 0.253) ( Figure 5).…”

“…Twenty-seven articles were included based on their abstracts. After reading full-text articles, 14 studies were included in this study [4,[21][22][23][24][25][26][27][28][29][30][31][32][33].…”

“…Four studies reported on the incidence of neutropenia [4,26,30,38]. Median incidence of neutropenia was 98% with a range from 40% to 100%.…”

The novel calicheamicin-conjugated CD22 antibody inotuzumab ozogamicin (CMC-544) effectively kills primary pediatric acute lymphoblastic leukemia cells

“…These problems could be partially solved by administration of multiple dosages of GO and by erasing the leukemic burden by chemotherapy before infusion of GO. 41 We expect that circulating CD22 þ cells will only limitedly hamper the efficacy of CMC-544 in ALL patients, as no complete saturation of CD22 Ags on ALL cells in the BM is required to obtain efficient CMC-544-induced cell death.…”

Efficacy and resistance of gemtuzumab ozogamicin for acute myeloid leukemia

“…Seventeen children with relapsed/refractory AML received GO (3 mg/m 2 on days 1, 4 and 7) plus AraC (100 mg/m 2 for 7 days) (GOCYT), and seven of these received GO-based consolidation [93]. The OR rate was 35 and 53 % after induction therapy and consolidation therapy with GO, respectively.…”