Inotuzumab Ozogamicin versus Standard Therapy for Acute Lymphoblastic Leukemia

Abstract

Background Inotuzumab ozogamicin, an anti-CD22 antibody conjugated to calicheamicin, is active in acute lymphoblastic leukemia. Methods In this phase 3 trial, adults with relapsed/refractory acute lymphoblastic leukemia were randomized to inotuzumab ozogamicin or standard intensive chemotherapy. Primary endpoints were complete remission and overall survival. Results Primary intent-to-treat (ITT) analysis of complete remission included the first 218 (inotuzumab ozogamicin, n=109; standard, n=109) of 326 patients randomized. Complete remission rate was significantly better with inotuzumab ozogamicin (80.7% [95% CI, 72%–88%] vs 29.4% [21%–39%]; P<0.001), as was minimal residual disease (MRD)-negativity among responders (78.4% [68%–87%] vs 28.1% [14%–47%]; P<0.001); remission duration was longer (median, 4.6 [3.9–5.4] vs 3.1 [1.4–4.9] months; hazard ratio=0.55 [0.31–0.96], P=0.034). More patients proceeded to transplant with inotuzumab ozogamicin (41%) versus standard (11%; P<0.001). In the ITT survival analysis (n=326), progression-free survival was significantly longer with inotuzumab ozogamicin vs standard (HR, 0.45 [97.5% CI, 0.34–0.61]; P<0.001; median, 5.0 [95% CI, 3.7–5.6] vs 1.8 [1.5–2.2] months). The overall survival HR was 0.77 (97.5% CI, 0.58–1.03); P=0.04; median was 7.7 (95% CI, 6.0–9.2) vs 6.7 (4.9–8.3) months. 2-year overall survival rate was 23% (95% CI, 16%–30%) vs 10% (5%–16%). In the safety population, the most frequent nonhematologic inotuzumab ozogamicin treatment-emergent grade ≥3 adverse events were liver-related. Any grade veno-occlusive liver disease occurred in 15 (11%) patients receiving inotuzumab ozogamicin. Conclusion Patients receiving inotuzumab ozogamicin versus standard care achieved higher response, MRD-negativity rates, and prolonged progression-free survival and overall survival. Veno-occlusive disease was a major non-hematologic toxicity.

Perspectives of Fc engineered antibodies in CD19 targeting immunotherapies in pediatric B-cell precursor acute lymphoblastic leukemia

“…9 , 11 , 15 CD22 specific immunotherapies (e.g. the ADC inotuzumab ozogamicin 35 and CD22 CAR T cells 28 ) or antibodies against myeloid targets may represent valid treatment options in that situation. A promising future concept for the therapy with Fc engineered antibodies is the combination of two antibodies of different specificities for simultaneous targeting of two antigens, which should hamper tumor escape by loss of one of the targets.…”

Immunotherapy in Pediatric Acute Leukemia: A Novel Magic Bullet or an Illusory Hope?

“…For example, CD22 is proven to be internalized on antibody binding. Inotuzumab ozogamicin is the antibody targeting CD22 linked to calicheamicin that showed improvement over chemotherapy including complete hematologic remission, longer progression-free, and overall survival [64,65]. The analog that could have been potentially used in AML is gemtuzumab ozogamicin, targeting CD33.…”

Hyper-CVAD + epratuzumab as a salvage regimen for younger patients with relapsed/refractory CD22-positive precursor B-cell acute lymphocytic leukemia

“…Patrice Chevallier, 1 Sylvain Chantepie, 2 Francoise Huguet, 3 Emmanuel Raffoux, 4 Xavier Thomas, 5 Thibaut Leguay, 6 Tony Marchand, 7 Francoise Isnard, 8 …”