Inotuzumab Ozogamicin Versus Standard Care for Acute Lymphoblastic Leukemia

作者：H. Kantarjian, D. DeAngelo, M. Stelljes, G. Martinelli, M. Liedtke, W. Stock, N. Gökbuget, S. O'brien, Kongming Wang, Tao Wang, M. L. Paccagnella, B. Sleight, E. Vandendries, A. Advani · 发表于：New England Journal of Medicine · 年份：2016 · DOI：10.1056/nejmoa1509277 · 被引用次数：1194 · 研究领域：Medicine

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 trea...