Radioimmunotherapy with yttrium-90-ibritumomab tiuxetan as part of a reduced- intensity conditioning regimen for allogeneic hematopoietic cell transplantation in patients with advanced non-Hodgkin lymphoma: results of a phase 2 study

Abstract

Forty patients were enrolled in this phase 2 study combining radioimmunotherapy (RIT) using yttrium-90-ibritumomab-tiuxetan (15 MBq [0.4 mCi]/kg) with reduced-intensity conditioning (RIC) using fludarabine (90 mg/m 2 ) and 2 Gy total body irradiation followed by allogeneic hematopoietic cell transplantation (HCT) from related (n ‫؍‬ 13) or unrelated (n ‫؍‬ 27) donors for the treatment of advanced non-Hodgkin lymphoma. Diagnoses were follicular lymphoma (n ‫؍‬ 17), chronic lymphocytic leukemia (n ‫؍‬ 13), mantle cell lymphoma (n ‫؍‬ 8), marginal zone lymphoma (n ‫؍‬ 1), and lymphoplasmacytic lymphoma (n ‫؍‬ 1). Median age was 55 years (range, 34-68 years). All patients were high risk with refractory disease or relapse after preceding autologous HCT. No additional toxicities attributable to RIT were observed. Engraftment was rapid and sustained. Incidences of acute graft-versus-host disease 2-4 and chronic graft-versus-host disease were 43% and 53%, respectively. Kaplan-Meierestimated nonrelapse mortality was 45% at 2 years. Twenty-two of 40 patients (55%) are alive, resulting in a KaplanMeier-estimated 2-year survival of 51% for all, 67% for follicular lymphoma, 49% for chronic lymphocytic leukemia, and 37% for mantle cell lymphoma patients. The combined use of RIT with RIC is feasible with acceptable toxicity, even in elderly and heavily pretreated patients. This study is registered at www.clinicaltrials.gov as #NCT00302757. (Blood. 2010;116(10): 1795-1802)

Dose-escalated radioimmunotherapy as part of reduced intensity conditioning for allogeneic transplantation in patients with advanced high-grade non-Hodgkin lymphoma

“…Previously, we reported a cohort of 40 patients treated with 90 Y-ibritumomab tiuxetan at a dose of 15 MBq/kg (0.4 mCi/kg) followed by RIC with fludarabine/2 Gy TBI and allogeneic HCT from MUD or MRD. 31 We observed moderate toxicity of this approach with main toxicities related to RIC and allogeneic HCT but not attributable specifically to RIT. Promising disease responses and long-term outcomes in particular in patients with FL and CLL have been observed.…”

TBI during BM and SCT: review of the past, discussion of the present and consideration of future directions

“…Such agents, recognizing and binding to CD20, are currently available for patients with B-cell non-Hodgkin's lymphoma, and have been employed as part of RIC regimens for allogeneic BMT in the phase II setting. 76 An agent targeted to BM would be penultimate in allowing directed delivery of radiation. Extensive work to extend the success of radioimmunotherapy to other forms of cancer is currently underway with goals of expanding cell surface targeting, and tailoring radionucleotides employed to specific clinical situations 77 (Table 3).…”

Hematopoietic Stem Cell Transplantation for Follicular Lymphoma : Optimal Timing and Indication

“…A German group reported a phase II study combining radioimmunotherapy (RIT) using 90 Y-ibritumomab tiuxetan with RIC using Flu and 2 Gy TBI followed by allo-SCT from related (n = 13) or unrelated donors (n = 27) for advanced NHL (17 FL, 13 chronic lymphocytic leukemia, 8 MCL, and 2 other histologies). 55 Disease status at SCT was CR in 7 patients, PR in 27 patients, and SD in 6 patients (i. e. 15% of chemorefractory disease). The 2-year OS and EFS for patients with FL were 67% and 57%, respectively.…”