Experience with 2 Dose Schedules of Inotuzumab Ozogamicin, Single Dose, and Weekly, in Refractory-Relapsed Acute Lymphocytic Leukemia (ALL)

CD22 expression occurs in more than 90% of patients with ALL. Inotuzumab ozogamicin, a CD22 monoclonal antibody bound to calicheamicin, is active in ALL.

Evaluate the efficacy and toxicity profiles of two schedules of inotuzumab, single-dose and weekly, in refractory-relapsed ALL.

Patients with refractory-relapsed ALL were eligible. Pediatric patients were allowed on therapy after 10 adults were treated. Eligibility criteria were standard including normal organ functions (renal, hepatic). The original single dose schedule gave inotuzumab at 1.3–1.8 mg/m2 IVq 3–4 weeks. After the initial 49 patients were treated, the schedule was modified to inotuzumab weekly, 0.8 mg/m2 D1, 0.5 mg/m2 D8 and 15, q 3–4 weeks. The latter schedule was based on higher invitro efficacy with more frequent exposure, and possible lower clinical toxicity.

83 patients were treated, 49 with single dose, and 34 with weekly dose. 29% were ≥ 60 yrs; 71% were in salvage 2 or beyond; only 8 (10%) were in salvage 1 with CRD1>12 months; 28% had Ph+ or t (4; 11); 10 (12%) had prior allogeneic SCT. Overall 14 patients (17%) achieved CR, 23 (28%) had CRP (no platelet recovery), and 9 (11%) had marrow CR (no recovery of counts), for an overall response rate of 46/83=55%. Response rate was 28/49 (57%) with single dose and 18/34 (53%) with weekly dose. Only 4 patients died in the first 4 weeks of therapy. Among 28 patients with cytogenetic abnormalities who achieved response, 25 (89%) achieved completed cytogenetic response. Among 44 patients who achieved response and had MRD studies by multi-parameter flow cytometry, 28 (64%) became MRD negative. The median survival was 5.4 months, 5.0 months with the single dose and 6.3 months with the weekly dose. Reversible grade 1–2 and 3–4 bilirubin elevations were observed in 24% and 4% respectively on single-dose and in 3% and 0% on weekly dose. Reversible grade 1–2 and 3–4 liver enzyme elevations were observed in 55% and 2% respectively on single-dose and in 21% and 6% respectively on weekly dose. Adverse factors for response included: salvage 2 or later vs. salvage 1 (49% vs. 71%); Ph+ and t(4; 11) abnormalities vs. others (39% vs. 62%). Allogeneic SCT was performed 22/49 patients (49%) on single-dose and in 9/34 (26%) so far (shorter follow-up) on weekly schedule: veno-occlusive disease was observed in 5/22 with single-dose (23%) and in 1/9 with weekly dose (11%).

Inotuzumab is highly active in refractory relapsed ALL. Weekly dose appears to be equally effective and less toxic than single dose.

Cortes:Pfizer: Consultancy, Research Funding. Jabbour:Pfizer: Honoraria.