90Y-Ibritumomab tiuxetan, fludarabine, and TBI-based nonmyeloablative allogeneic transplantation conditioning for patients with persistent high-risk B-cell lymphoma

Abstract

Nonmyeloablative allogeneic transplantation (NMAT) infrequently cures active chemoresistant, bulky, or aggressive B-cell lymphoma (B-cell non-Hodgkin lymphoma [B-NHL]). We hypothesized that ⁹⁰Y-ibritumomab tiuxetan-based NMAT would facilitate early cytoreduction in such patients promoting improved long-term disease control by the allogeneic graft. Forty high-risk B-NHL patients with persistent disease received 0.4 mCi/kg (maximum, 32 mCi/kg) ⁹⁰Y-ibritumomab tiuxetan, fludarabine, and 2 Gy total body irradiation and matched-related (15) or unrelated (25) transplantation. Baseline features included: median age, 58 years (range, 29-69 years); median prior regimens, 6 (range, 3-12); chemosensitive disease, 6 (15%); bulk > 5 cm, 17 (range, 5.2-18.6 cm, 43%); diffuse large B-cell lymphoma, 14 (35%); and comorbidity score > zero, 34 (85%). Early responses were observed in 24 (60%, 14 complete remission/complete remission unconfirmed, 10 partial response) patients, including 17 of 29 (59%) with chemotherapy-resistant disease and 10 (59%) with bulk > 5 cm. The estimated 30-month survival, progression-free survival, and nonrelapse mortality were 54.1%, 31.1%, and 15.9%, respectively. Early response, baseline platelet counts over 25 000/μL, indolent histology, and related donors were associated with improved survival. The addition of ⁹⁰Y-ibritumomab tiuxetan to NMAT is safe and yields early responses and prolonged disease control in some of the highest-risk B-NHL patients. This trial was registered at www.clinicaltrials.gov as #NCT00119392.

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

“…In a recent retrospective analysis Soiffer et al 37 could show that the use of in vivo T-cell depletion in the context of RIC leads to a significant increase in the rate of relapse. Furthermore, disease stage and pace of relapse in the patient with aggressive NHL as treated within this study precluded a meaningful strategy of preemptive additional DLI after in vivo T-cell depletion as propagated for FL by Thomson et al 38 This may also explain why the use of additional dose-escalated RIT combined with RIC in our case did not lead to a lower incidence of relapse compared with less intense RIC regimens without or with RIT as reported by Gopal et al and Rezvani et al 32,39 For future studies, we therefore would suggest omitting additional in vivo T-cell depletion using alemtuzumab.…”

“…However, NRM was 45% at 2 years, most probably related to the high-risk patient cohort treated. Recently, Gopal et al 32 reported a similar approach using the same RIC and reported a NRM of only 16%, which may have been the result of a different patient selection.…”

“…Furthermore, in a cohort of patients with high-grade NHL using the same RIC but without additional RIT, Morris et al 6 reported an estimated 3-year NRM of 38%. However, Gopal et al 32 reported in their study of standard dose RIT using 90 Y-ibritumomab tiuxetan combined with a conditioning with fludarabine/2 Gy TBI in a similar high-risk cohort of patients an incidence of NRM of only 16%. Therefore, the relatively high NRM in our study might be also related to the RIC regimen used including alemtuzumab as GvHD prophylaxis.…”

The current therapeutic scenario for relapsed mantle cell lymphoma

“…The addition of radioimmunotherapy (RIT) to allo-SCT procedures has shown only conflicting results so far [65,66]. In conclusion, the issue of tolerability of such an immunological strategy is essential, as the high NRM (along with the high relapse rate) remains the major limitation for the application of allo-SCT in relapsed MCL.…”

The role of allogeneic haematopoietic progenitor cell transplantation in patients with diffuse large B-cell non-Hodgkin lymphomas (DLBCL)

“…Several studies have shown that the use of 90 Y-ibritumomab tiuxetan or 131 I-tositumomab in combination with high-dose chemotherapy and auto-HCT have no detectable effect on engraftment and has a toxicity profile similar to that of conventional conditioning regimens. [45][46][47] Gopal et al 48 recently reported the results of a prospective phase II study evaluating a conditioning regimen of 90 Y-ibritumomab tiuxetan with fludarabine and low-dose TBI in 40 high risk B-cell NHL patients who underwent allo-HCT with persistent disease at the time of transplantation. This study included 14 patients (35%) with DLBCL, 8 patients (20%) with mantle cell NHL and 18 patients (45%) with indolent NHL.…”