A phase 2 study of inotuzumab ozogamicin and rituximab, followed by autologous stem cell transplant in patients with relapsed/refractory diffuse large B-cell lymphoma

• Published in: Leukemia & lymphoma 2015-10, Vol.56 (10), p.2863-2869
• Main Authors: Wagner-Johnston, Nina D, Goy, Andrè, Rodriguez, Maria A, Ehmann, W Christopher, Hamlin, Paul A, Radford, John, Thieblemont, Catherine, Suh, Cheolwon, Sweetenham, John, Huang, Yifan, Sullivan, Sharon T, Vandendries, Erik R, Gisselbrecht, Christian
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antibodies, Monoclonal, Humanized - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Drug Resistance, Neoplasm; Female; Hematopoietic Stem Cell Mobilization - methods; Hematopoietic Stem Cell Transplantation - adverse effects; Hematopoietic Stem Cell Transplantation - methods; Humans; Kaplan-Meier Estimate; Lymphoma, Large B-Cell, Diffuse - diagnosis; Lymphoma, Large B-Cell, Diffuse - mortality; Lymphoma, Large B-Cell, Diffuse - therapy; Male; Middle Aged; Neoplasm Staging; Odds Ratio; Peripheral Blood Stem Cell Transplantation - adverse effects; Peripheral Blood Stem Cell Transplantation - methods; Prognosis; Recurrence; Remission Induction; Retreatment; Rituximab - administration & dosage; Transplantation Conditioning; Transplantation, Autologous; Treatment Outcome; Young Adult
• ISSN: 1042-8194; 1029-2403
• DOI: 10.3109/10428194.2015.1017821

This study evaluated the safety and efficacy of inotuzumab ozogamicin (INO), a targeted humanized anti-CD22 antibody conjugated to calicheamicin, plus rituximab (R-INO) every 3 weeks, up to six cycles, followed by high dose therapy and autologous stem cell transplant (HDT-aSCT) in patients with high-risk relapsed/refractory diffuse large B-cell lymphoma (DLBCL). The primary endpoint was overall response (OR) rate after three cycles of R-INO. Sixty-three patients were enrolled. Common grade 3/4 adverse events during R-INO treatment were thrombocytopenia, lymphopenia and neutropenia. OR rate after three cycles of R-INO was 28.6% (95% confidence interval: 17.9-41.4). Eighteen patients underwent HDT-aSCT; 2-year progression-free survival (PFS) for these patients was 61.1%. Serious infections and hepatic toxicity following aSCT occurred in 33% and 22%, respectively. One- and 2-year PFS rates for all enrolled patients were 28.9% and 25.3%, respectively (median, 3.0 months). R-INO had lower than expected activity as a salvage regimen for transplant eligible patients with DLBCL.