Radioimmunotherapy in non-Hodgkin's lymphoma (NHL) using a fractionated schedule of DOTA-conjugated, 90Y-radiolabeled, humanized anti-CD22 monoclonal antibody, epratuzumab

Abstract

2545 Background: A phase I/II, multi-center, dose-escalation trial was conducted to establish the safety, optimal dosing, and preliminary efficacy of 90Y-epratuzumab administered weekly for 2 or 3 consecutive wks to pts with B-cell NHL who failed ≥1 regimen of standard chemotherapy. Methods: Eligibility criteria included <25% BM involvement, plts >100,000 cells/mm3, and measurable disease by CT with no single mass >10 cm. Pts received 1.5 mg/kg/wk epratuzumab with 111In-epratuzumab co-administered the 1st wk. Twenty-six pts with a median of 3 prior treatments have been treated, including 15 pts without prior bone marrow transplant (BMT) at 5–10 mCi/m2/wk (total 90Y dose, 15–22.5 mCi/m2) and11 pts with prior BMT escalated separately at 2.5–5 mCi/m2/wk (total 90Y dose, 5–10 mCi/m2). Results: Dose escalation is continuing, with no serious AEs considered treatment-related. One pt in each escalation arm had protocol-defined DLT (>12 wk platelet recovery); otherwise, therapy was well tolerated with no significant toxicity besides transient hematologic depression, including 4 pts retreated without additional toxicity. 111In imaging demonstrated antibody tumor targeting, and hot/cold PK demonstrated stability of DOTA chelation ≥1 wk. In 22 pts with treatment evaluations, 13 pts (59%) had an objective response (OR) by IWG criteria, including pts with and without BMT [5/9 (56%) and 8/13 (62%), respectively], with indolent and aggressive disease [8/10 (80%) and 5/12 (42%), respectively], across histologies [follicular NHL, 9/12 (75%); DLCL, 2/4 (50%); mantle cell, 2/6 (33%)], and in pts failing rituximab (9/15, 60%). Most OR's were complete responses (CR/CRu, 9/13, 69%), and 3/5 pts assessed after CR onset now have responses >6 mo, including 2 pts continuing >1 yr. Conclusion: This study shows the feasibility and safety of a dose-fractionation schedule of a 90Y-labeled anti-CD22 Mab, obtaining therapeutic responses across all pt groups, including durable complete responses, and achieving higher cumulative doses than other RAIT agents given as single doses. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Immunomedics Immunomedics Immunomedics Immunomedics