Author:

Keywords:

Science & Technology, Life Sciences & Biomedicine, Oncology, B-CELL LYMPHOMA, CD22-TARGETED IMMUNOCONJUGATE, ANTITUMOR EFFICACY, SALVAGE THERAPY, CALICHEAMICIN, CHEMOTHERAPY, CMC-544, POTENT, FAMILY, Adult, Aged, Antibodies, Monoclonal, Humanized, Antibodies, Monoclonal, Murine-Derived, Antineoplastic Combined Chemotherapy Protocols, Drug Administration Schedule, Female, Humans, Hyperbilirubinemia, Inotuzumab Ozogamicin, Liver, Liver Cirrhosis, Liver Failure, Lymphoma, Non-Hodgkin, Male, Middle Aged, Molecular Targeted Therapy, Neutropenia, Prognosis, Recurrence, Risk Factors, Rituximab, Thrombocytopenia, Treatment Outcome, 1103 Clinical Sciences, 1112 Oncology and Carcinogenesis, Oncology & Carcinogenesis, 3211 Oncology and carcinogenesis

Abstract:

PURPOSEInotuzumab ozogamicin (INO) is an antibody-targeted chemotherapy agent composed of a humanized anti-CD22 antibody conjugated to calicheamicin, a potent cytotoxic agent. We performed a phase I/II study to determine the maximum-tolerated dose (MTD), safety, efficacy, and pharmacokinetics of INO plus rituximab (R-INO) for treatment of relapsed/refractory CD20(+)/CD22(+) B-cell non-Hodgkin lymphoma (NHL). PATIENTS AND METHODSA dose-escalation phase to determine the MTD of R-INO was followed by an expanded cohort to further evaluate the efficacy and safety at the MTD. Patients with relapsed follicular lymphoma (FL), relapsed diffuse large B-cell lymphoma (DLBCL), or refractory aggressive NHL received R-INO every 4 weeks for up to eight cycles.ResultsIn all, 118 patients received one or more cycles of R-INO (median, four cycles). Most common grade 3 to 4 adverse events were thrombocytopenia (31%) and neutropenia (22%). Common low-grade toxicities included hyperbilirubinemia (25%) and increased AST (36%). The MTD of INO in combination with rituximab (375 mg/m(2)) was confirmed to be the same as that for single-agent INO (1.8 mg/m(2)). Treatment at the MTD yielded objective response rates of 87%, 74%, and 20% for relapsed FL (n = 39), relapsed DLBCL (n = 42), and refractory aggressive NHL (n = 30), respectively. The 2-year progression-free survival (PFS) rate was 68% (median, not reached) for FL and 42% (median, 17.1 months) for relapsed DLBCL. CONCLUSIONR-INO demonstrated high response rates and long PFS in patients with relapsed FL or DLBCL. This and the manageable toxicity profile suggest that R-INO may be a promising option for CD20(+)/CD22(+) B-cell NHL.