Radionuclide therapy of B-NHL with Y-90 epratuzumab: A report of the multi-centre trial

Full text: The advantages of increased efficacy of RAIT compared to the naked antibody are at expense of temporary reversible bone marrow suppression. An ongoing, phase I/II, multi-center, dose escalation trial in patients with relapse of a B-NHL is assessing safety and efficacy of Y-90-epratuzumab administered weekly for 2 or 3 consecutive weeks to achieve relatively high fractionated Y-90 doses (> 5 mCi/kg BW). Patients with indolent and aggressive NHL who failed prior therapy were eligible for this study. Thirty-seven patients have been revealed into two dose groups without achieving MTD (total 90Y dose, 30 mCi/m2) There were 18 follicular, 10 mantle cell, and DLBC-NHL. In 16 cases there was a foregoing BMT. The therapy consisted of 2-3 weekly injections of 2 Y-90-hLL2 in dose steps of 3x5 3x10 mCi/m2 (high-dose group without BMT) or 2x2.5 mCi/m2 (low-dose group with prior BMT). In the frame of the first infusion there was added In-111-hLL2 to check the targeting of the tumour by imaging at day 3-5 post injection. In the low-dose group in 2 cases there were hematologic DLT noticed so that in this group MTD was achieved. In the high- dose group at 3x10 mCi/m2 there was only one DLT obvious. Except these non-lethal cytopenias no significant toxicity was noticed. Also a HAMA induction was not substantiated. Five patients without additional toxicity were treated a second time Of the 37 patients, 23 (62%) had an objective response (OR) by IWG criteria, including patients with indolent and aggressive disease [12/17 (70%) and 11/20 (55%), respectively], across histologies [follicular NHL, 13/18 (72%); DLBCL, 7/9 (78%); mantle cell, 4/10 (40%)], and in patients failing rituximab (10/16, 63%). Most ORs were complete responses (CR/CRu, 15/23), and with follow-up now available in 15 CR/Cru responders, all had responses ≥23 mo, including 2 patients continuing > 2.5 yrs. Dose escalation continues after 5/6 patients (83%) in the last cohort receiving 10 mCi/ m2 x 3 weekly infusions had an objective response, including 4 patients with CR/CRu. In conclusion, this fractionated schedule of 90Y-labeled humanized anti-CD22 antibody appears safe and efficacious in patients with recurrent NHL. Dose escalation continues after achieving 65% complete responses at a 30 mCi/m2 cumulative 90Y-dose