Phase I trial of ⁹⁰Y-ibritumomab tiuxetan in patients with relapsed B-cell non-Hodgkin's lymphoma following high-dose chemotherapy and autologous stem cell transplantation

Abstract

Between January 2001 and September 2005, 19 patients with progressive B-cell non-Hodgkin's lymphoma were treated with a cohort-specific dose of yttrium-90 ibritumomab tiuxetan (0.10 - 0.20 mCi/kg) to determine appropriate dosing in patients who had previously received high-dose chemotherapy and autologous stem cell transplantation (ASCT). Patients were required to have adequate end organ function and bone marrow status. Patients had been treated with a median of three prior therapies (range, 1 - 9). The median time from ASCT to radioimmunotherapy was 28 months. Hematologic toxicities were dose-limiting and included grade 3 - 4 thrombocytopenia (53%), neutropenia (32%), and anemia (21%). The majority of grade 3 - 4 events occurred at the 0.2 mCi/kg dose level. Nine patients responded (complete response, complete response unconfirmed, or partial response) to the therapy. At a median follow-up of 37 months, the 1-year event-free and overall survival rates were 26% and 57%, respectively. A dose of 0.2 mCi/kg ibritumomab tiuxetan is safe and effective for patients with progressive disease after high-dose chemotherapy and ASCT.

Radioimmunotherapy with 90Y-ibritumomab tiuxetan is a safe and efficient treatment for patients with B-cell lymphoma relapsed after auto-SCT: an analysis of the international RIT-Network

“…In addition, efficacy and safety of RIT had also been shown for limited numbers of patients, who had been treated for relapsed disease after ASCT. [6][7][8] The data of this report, obtained in the real-life setting of an international registry, confirm the feasibility of RIT in patients after ASCT and corroborate the value of 90 Y-ibritumomab tiuxetan as particularly potent treatment modality to obtain clinically meaningful, in part long-lasting remissions in patients with relapsed B-cell lymphoma. …”

“…Thus we documented significant, particularly delayed hematotoxicities in this cohort of heavily pretreated patients, exceeding those previously reported. [6][7][8] Comparing the quartiles of patients with lowest and those with the most severe hematotoxicity, we found no differences between such patient groups regarding age, tumor stage, previous chemotherapies, line of therapy, histologic subtype of the lymphoma, BM infiltration, days from transplantation to RIT, dose of radionuclide and indication for RIT. The overall response rate to RIT was 53%, with best responses representing CR in 30, PR in 14 and s.d.…”

“…[1][2][3][4][5] As to the marrow toxicity of RIT, patients with a history of ASCT had been excluded from most trials, resulting in only limited data on the safety and efficacy of RIT in patients with relapsed disease after ASCT. 6,7 However, a phase 1 clinical trial of Vose et al 5 recently documented the feasibility of RIT with ibritumomab tiuxetan up to dose levels of 0.2 mCi/kg, providing a rationale to offer RIT also to patients after ASCT. We here summarize retrospective data collected outside clinical trials from 109 patients treated with RIT for lymphoma relapsed after ASCT, as reported to the international RIT registry (RIT-NT).…”

Second hematopoietic SCT for lymphoma patients who relapse after autotransplantation: another autograft or switch to allograft?

“…Recently, Vose et al 14 reported the use of yttrium-90 ibritumomab tiuxetan in 19 patients with B-cell NHL who progressed after auto-HSCT. These patients were treated with a cohort-specific yttrium-90 ibritumomab tiuxetan dose.…”

Radioimmunotherapy for B-cell lymphoma: Y90 ibritumomab tiuxetan and I131 tositumomab

“…A CR was achieved in 1/3 patients with FL. By contrast, the approach of Vose et al (2003) was to perform a dose-escalation study with Y 90 ibritumomab tixuetan. Sixteen patients were treated in three cohorts, the highest dose administered being 0.2 mCi/kg; in this group, the majority of grade 4 haematological toxicities occurred and contrasts to the experience with full dose, Y 90 ibritumomab tiuxetan reported above.…”