Preliminary results of gemtuzumab ozogamicin (GO) during myeloablative conditioning for allogeneic stem cell transplantation (AlloSCT) or following reduced intensity alloSCT (RI-AlloSCT) in children with AML

Abstract

7038 Background: CD33 is expressed in 80–90% of childhood AML. GO, an immunotoxin targeting CD33, induces remission in 20–30% of relapsed/refractory childhood AML. Standard myeloablative conditioning (MAC) for AlloSCT in children with standard risk AML (SR-AML) is BU/CY. However, this regimen may be associated with 32% transplant related mortality (TRM) and 25% risk of relapse in SR-AML (Woods et al, Blood, 2001). Outcome following AlloSCT for high risk (HR) AML (≥CR3, induction failure [IF], refractory disease) is dismal (≤10% OS). There is a need for novel therapy during conditioning and after AlloSCT that can reduce TRM and relapse in SR-AML and improve outcome in HR-AML. Methods: We have performed 2 phase I studies of GO. In the first study of CD33+ HR-AML GO was dose escalated on day - 14 (3–7.5 mg/m2) prior to BU /CY MAC regimen. In the 2nd study of CD33+ SR-AML 2 doses of GO (4.5- 9 mg/m2) were administered ≥60d post reduced intensity conditioning (RIC) AlloSCT (8 wks apart). Results: In the HR-AML study, ten pts (2 CR3, 5 IF, 3 refractory) were studied. One pt died of chronic GVHD, 4 died of progressive disease, and 5 remain alive with no evidence of disease (NED). One pt developed mild VOD that resolved without therapy. In the SR-AML study, 11 pts, (8-CR1 and 3-CR2), received BU/FLU RIC. Nine pts received two doses of GO (Table) at mean d+78 and +153, respectively. One pt received one dose of GO but relapsed and died. One pt had primary graft failure. Nine pts are alive with NED; 1pt died from cGVHD. There has been no DLT secondary to GO and the MTD of GO in each study has not been reached. Conclusion: GO has been safe and well tolerated either added to MAC in children with HR-AML or as consolidation following RI-AlloSCT in SR-AML. We are currently accruing patients at the final dose level of GO in both studies. Study Conditioning GO Dose Median Age(range) Donors Myeloid Recovery (days) ANC>500/mm3× 2 days Platelet Recovery (days)(> 20,000/mm3 × 7 days UNTX) Mean Donor ChimerismDay-30 HR-AML Myeloablative 3mg/m2 [n=3] 8 yr 1 6/6 HLA-MSD, 24±10 54±49 96%±5 BU:12.8–16mg/kg 4.5mg/m2[n=3] (0.75-17) 1 10/10 MUD CY:120 mg/kg± ATG 6mg/m2 [n=3] 8 UCB (3 6/6, 2 5/6 and 3 4/6) 7.5mg/m2[n=1] SR-AML Reduced Intensity 4.5mg/m2[n=3], 11 years 8 6/6 HLA-MSD 15±4 16±16 97±2% BU:6.4–8mg/kg 6mg/m2 [n=4], (0.5-21) 1 5/6 MRD FLU: 150mg/kg ± ATG 7.5mg/m2 [n=3] 2 4/6 UCB. No significant financial relationships to disclose.