1 research outputs found
Phase 1 study of inotuzumab ozogamicin combined with R-GDP for the treatment of patients with relapsed/refractory CD22+ B-cell non-Hodgkin lymphoma
<p><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).</p> <p><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>β=β27). Part 2 (<i>n</i>β=β10) confirmed safety and tolerability; Part 3 (<i>n</i>β=β18) evaluated preliminary efficacy.</p> <p><b>Results:</b> Among 55 patients enrolled, 42% were refractory at baseline (median 2 [range, 1β6] prior therapies); 38% had diffuse large B-cell lymphoma (DLBCL). The highest dosage regimen with acceptable toxicity was InO 0.8βmg/m<sup>2</sup>, rituximab 375βmg/m<sup>2</sup>, cisplatin 50βmg/m<sup>2</sup>, gemcitabine 500βmg/m<sup>2</sup> (day 1 only) and dexamethasone 40βmg (days 1β4); this was confirmed in Part 2, in which three patients had dose-limiting toxicities (grade 4 thrombocytopenia [<i>n</i>β=β2], febrile neutropenia [<i>n</i>β=β2]). Most frequent treatment-related adverse events were thrombocytopenia (any grade, 85%; grade β₯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>β=β14), DLBCL (<i>n</i>β=β21), and mantle cell lymphoma (<i>n</i>β=β13), respectively.</p> <p><b>Conclusions:</b> InO 0.8βmg/m<sup>2</sup> 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).</p