Inotuzumab ozogamicin (INO) is a humanized anti-CD22 antibody conjugated to calicheamicin. CD22 is expressed on the majority of B-cell non-Hodgkin's lymphomas (B-NHL). This phase II study evaluated the safety and efficacy of INO in patients (patients) with CD22+ indolent B-NHL refractory to rituximab (R), R plus chemotherapy, or radioimmunotherapy (RIT).Methods
Patients that had progressed after ≥2 systemic therapies with no response/progression within 6 mo of R-containing therapy or 12 mo of RIT were enrolled. Patients received INO 1.8 mg/m2 every 28 days for 4 to 8 cycles, with dose/frequency adjusted based on toxicity.Results
81 patients (72 follicular lymphoma [FL], 4 marginal zone, 5 small lymphocytic lymphoma) have been enrolled: the median age was 63 years (29–84 years), 54% were male, and 65% had >2 prior anticancer regimens. Based on the Follicular Lymphoma International Prognostic Index, 24%, 28%, and 48% of FL patients, respectively, were low, intermediate, and high risk. Treatment-emergent adverse events (AEs; >30% all grades/ ≥ 5% grade ≥3) were thrombocytopenia (69%/57%), neutropenia (51%/26%), nausea (48%/5%), fatigue (47%/3%), AST increased (43%/4%), lymphopenia (36%/12%), leukopenia (32%/9%), and GGT increased (20%/6%). Seventeen patients reported 35 serious AEs. Twenty-six patients reported 35 AEs that led to discontinuation (thrombocytopenia , neutropenia , GGT increased , hyperbilirubinemia , leukopenia, Budd-Chiari syndrome, hepatic cirrhosis, abnormal hepatic function, pneumonia, and blood alkaline phosphatase [1 each]). In 74 evaluable patients, overall response rate (ORR) was 58% (in 65 FL patients, ORR was 63%, including 32% with complete response). The progression-free survival rate at 12 months was 52%. Thirteen deaths (disease progression , other ) were reported, all >30 days after the last dose of INO.Conclusions
In patients with indolent B-NHL refractory to R-containing therapy or RIT, INO showed definitive clinical activity and had a safety profile similar to that previously reported.