Inotuzumab Ozogamycin (I0), a CD22 Monoclonal Antibody Conjugated to Calecheamicin, Is Active in Refractory-Relapse Acute Lymphocytic Leukemia (R-R ALL)

Patients (pts) with R-R ALL have a poor prognosis. CD22 is highly expressed in ALL. IO is active in CD22-positive lymphomas. Methods: Pts with R-R ALL received IO 1.8 mg/m2 IV over 1hr every 3 weeks. First 3 pts received 1.3 mg/m2 in course 1. Children were eligible for study after 10 adults were treated; first 3 children received 1.3 mg/m2. Study started June 2010. Results: 49 pts were treated. Median age 36 yrs (range 6–80); 12 pts ≥ 60 yrs; Ph+ in 7, t(4:11) in 5, other abnormalities in 25. CD22 expressed in > 50% blasts in all pts, > 90% in 28. Median number courses so far 2 (1–5). 13 pts received IO as salvage 1 (S1), 24 as salvage 2 (S2), 12 as ≥ salvage 3 (S3). 7 pts had allo SCT before IO. Overall, 9/49 pts (18%) achieved CR, 5 had marrow CR (10%), 14 had CRp (29%), 21 were resistant, 2 died within 4 wks. Overall, CR+mCR+CRp (OR) was 57%: S1 9/13 (54%); S2 11/24 (46%); S3 8/12 (67%). A lower response rate was noted in Ph-positive ALL (3 of 7 = 43%) and in t (4;11) (1 of 5 = 20%) otherwise there were no clear correlations between OR and pts/ALL characteristics or with CD22 expression ≥ vs. < 90%. In 24 pts with evaluable pharmacokinetics studies: 3-hr I0 level > 100 ng/ml associated with OR in 8/9 vs. 5/15 if I0 level < 100 ng/ml. Median survival 5.1 months: S1 not reached (65% at 8 mos), S2 4.1 mos, ≥ S3 6.7 mos. Median response duration, CR+mCR+CRp (OR), not reached (estimated 70% at 8 mos). Median survival in 28 responders 7.9 mos. Fever and mild hypotension occurred in most pts on days 1–2 and resolved with support. Liver function abnormalities (LFA) were noted as IO related in 32 (67%), severe in 4 (13%). 2 pts had liver biopsies showing periportal fibrosis (after 1 and 4 courses). 20 pts were able to proceed to allo SCT (19 in remission, 1 with active ALL); 5 pts post-allo SCT developed veno-occlusive disease, 2 receiving second allo SCT, 4 receiving thio-TEPA + clofarabine as part of their preparative regimen. Conclusions: IO is highly active in R-R ALL. LFAs occur and are reversible. Study of IO weekly schedule is ongoing. IO and chemotherapy combinations should be pursued.

Cortes:Pfizer: Consultancy, Research Funding. Kantarjian:Novartis: Consultancy, Research Funding; Pfizer: Research Funding; BMS: Research Funding.