Phase 1 study of inotuzumab ozogamicin combined with R-GDP for the treatment of patients with relapsed/refractory CD22+ B-cell non-Hodgkin lymphoma

<b>Objective</b>: To evaluate safety, tolerability, and preliminary activity of inotuzumab ozogamicin (InO) plus rituximab, gemcitabine, dexamethasone, and cisplatin (R-GDP) in patients with relapsed/refractory CD22+ B-cell non-Hodgkin lymphoma (NHL). <b>Methods</b>: Patients received InO plus R-GDP (21-day cycle; six-cycle maximum) using up-and-down dose-escalation schema for gemcitabine and cisplatin to define the highest dosage regimen(s) with acceptable toxicity (Part 1; <i>n</i> = 27). Part 2 (<i>n</i> = 10) confirmed safety and tolerability; Part 3 (<i>n</i> = 18) evaluated preliminary efficacy. <b>Results:</b> Among 55 patients enrolled, 42% were refractory at baseline (median 2 [range, 1–6] prior therapies); 38% had diffuse large B-cell lymphoma (DLBCL). The highest dosage regimen with acceptable toxicity was InO 0.8 mg/m², rituximab 375 mg/m², cisplatin 50 mg/m², gemcitabine 500 mg/m² (day 1 only) and dexamethasone 40 mg (days 1–4); this was confirmed in Part 2, in which three patients had dose-limiting toxicities (grade 4 thrombocytopenia [<i>n</i> = 2], febrile neutropenia [<i>n</i> = 2]). Most frequent treatment-related adverse events were thrombocytopenia (any grade, 85%; grade ≥3, 75%) and neutropenia (69%; 62%). Overall (objective) response rate (ORR) was 53% (11 complete, 18 partial responses); ORR was 71%, 33%, and 62% in patients with follicular lymphoma (<i>n</i> = 14), DLBCL (<i>n</i> = 21), and mantle cell lymphoma (<i>n</i> = 13), respectively. <b>Conclusions:</b> InO 0.8 mg/m² plus R-GDP was associated with manageable toxicity, although gemcitabine and cisplatin doses were lower than in the standard R-GDP regimen due to hematologic toxicity. Evidence of antitumor activity was observed; however, these exploratory data should be interpreted with caution due to the small sample size and short follow-up duration (Clinicaltrials.gov number: NCT01055496).