Gemtuzumab ozogamicin with cytarabine and mitoxantrone as a third-line treatment in a poor prognosis group of adult acute myeloid leukemia patients: a single-center experience

Abstract

We analyzed the safety and efficacy of gemtuzumab ozogamicin (GO) combined with cytarabine and mitoxantrone in the treatment of 21 patients with acute myeloid leukemia (11 refractory and 10 in second relapse). Patients' median age was 52 years (range 36-68); all patients had previously been treated with anthracycline-containing regimens (daunorubicin and idarubicin). GO at a dosage of 3 mg/m2 was administered as a 2-h intravenous infusion on days 1 and 14, cytarabine at 100 mg/m2 on days 1-7, and mitoxantrone at 12 mg/m2 on days 1-3. Infusion-related events were observed in 15 of 21 (71.4%) patients. The incidence of grade 1 or 2 elevations of bilirubin and hepatic transaminases was 4 of 21 (19%) and 3 of 21 (14.2%). In response to chemotherapy, 2 of 21 (9.5%) achieved complete remission and 2 of 21 (9.5%) achieved complete remission with incomplete platelet recovery, with an overall remission rate of 4 of 21(19%); median survival of these 4 patients was 7 months. Four of 21 patients (19%) died during aplasia after chemotherapy; no veno-occlusive disease occurred. No treatment-related cardiotoxicity or cerebellar toxicity was observed. In our experience, the addition of GO to mitoxantrone and cytarabine is feasible in refractory or second relapse acute myeloid leukemia patients but yields a low response rate when used as a third-line treatment.

Gemtuzumab ozogamicin in the treatment of adult acute myeloid leukemia

“…A number of GO-containing combination chemotherapies for relapsed and refractory AML have been reported (Table 3) [31][32][33][34][35][36][37][38][39][40][41][42]. The response rates observed in these studies range from 12% to 68% and appear to increase as time progresses.…”

Sequence of administration and methylation of SOCS3 may govern response to gemtuzumab ozogamicin in combination with conventional chemotherapy in patients with refractory or relapsed acute myelogenous leukemia (AML)

“…During myelosuppression, in almost all patients (88%) neutropenic fever emerged and four patients (17%) subsequently died due to infectious complications. Treatment-related mortality was reported to be 5-13% in published studies using GO after chemotherapy [22,33,36], whereas mortality in studies using GO before chemotherapy seemed to be higher (19-57%) [8,11,37,43]. Of note, multiple responses were observed in a single patient treated repeatedly with GO.…”

“…In studies, whose GO was administered within a few days before chemotherapy, CR was achieved in 9.5-55% with a median OS of 2 to 8.2 months [8,11,[29][30][31][32]. Chemotherapy followed by GO resulted in 10-70% CR and a median OS of 2.3 to 11 months [22,[33][34][35][36].…”

“…Gemtuzumab ozogamicin (GO) is a humanized monoclonal murine Ig4 antibody which is linked to the potent antitumor antibiotic calicheamicin and targets the CD33 antigen [6][7][8][9][10][11]. After internalization, calicheamicin is cleaved from the antigen-antibody complex and induces DNA doublestrand breaks and apoptosis by sequence specific binding to DNA [6,9,11].…”

“…After internalization, calicheamicin is cleaved from the antigen-antibody complex and induces DNA doublestrand breaks and apoptosis by sequence specific binding to DNA [6,9,11]. CD33 is expressed on 90-99% of AML blasts, myeloid precursors cells, macrophages, monocytes, and dendritic cells, but not on hematopoietic stem cells [9,11]. CD33 is member of the sialic acid-binding immunoglobulin-like lectin (Siglec) family of inhibitor receptors, and its activation induces apoptosis and inhibition of proliferation in AML cells.…”