Gemtuzumab Ozagamicin Is Well Tolerated as Post-Consolidation Therapy in Childhood AML.

The NOPHO-AML 2004 protocol includes a post-consolidation randomization to Gemtuzumab ozagamicin, (GO, Mylotarg) or no further therapy. Randomization is offered to all standard-risk patients and to high-risk patients without a donor for SCT. GO is administered as a 2-hour infusion of 5 mg/m² at least four weeks after the last consolidation including high-dose cytarabine and etoposide (HA₂E). GO is repeated following a scheduled interval of three weeks. By August 2007 a total of 45 patients have been randomized (39 with standard-risk and 6 with high-risk AML). An additional nine patients were eligible but not randomized due to clinical decision (n=2), parental refusal (n=6), or administrative error (n=1). Twenty-three were randomized to receive GO. Detailed toxicity data were available from 21 of these patients. The median age was 3 years (six patients less than 2 years of age) at the time of GO. The median interval from HA₂E to first GO was 32 days (range 27 – 43). The median interval from first to second GO was 22 days (range 20 – 28). All randomized patients received the second GO except one who relapsed shortly after the first infusion. No major events were reported in relation to the infusion. ALAT showed a slight elevation from a median baseline of 64 U/L to a median peak of 82 U/L and bilirubin increased from a median baseline of 5 μmol/L to a median peak of 8 μmol/L; highest value 25 μmol/L. No patients showed signs of VOD. No significant decrease in hemoglobin was observed whereas all patients became severely leukopenic (median nadir WBC 0.6) and neutropenic (median nadir ANC 0.1). Recovery to ANC > 0.5 lasted a median of 14 days (range 0 – 21). Fever needing antibiotic treatment occurred following 8 of 40 GO courses. None of the infectious episodes were life-threatening. Only a modest decline in platelet count was noted, median nadir 77 (range 10 – 239). Platelet transfusion was given following 5 of 40 GO courses. In conclusion GO infusion was well tolerated without clinical liver toxicity. Severe neutropenia was common but antibiotics were necessary following only 20% of the courses. Thrombocytopenia was modest.