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.

Figure 1

Treatment schema. CSP indicates cyclosporine; and MMF, mycophenolate mofetil.

Figure 2

Waterfall plot of day 84 response after ⁹⁰Y-ibritumomab tiuxetan-based NMAT by histology and chemoresistance. HCL indicates hairy cell leukemia. For the 4 patients who died before day 84, the most recent response data before death were used.

Figure 3

Early response in bulky, chemoresistant lymphoma. A 33-year-old woman with CLL/SLL had a partial response lasting 10 months after initial therapy with 6 cycles of fludarabine-R and then experienced progressive disease while receiving pentostatin-cyclophosphamide-R, and continued progressive disease while receiving CHOP. (A) Baseline image reveals a dominant 12 cm left submandibular mass. She was treated with 32 mCi of ⁹⁰Y-ibritumomab tiuxetan, fludarabine, 2 Gy TBI, and a matched unrelated allogeneic transplant and achieved a PR by after transplantation day 28 (B) and complete remission by day 84. The patient remains alive and disease-free 3 years after transplantation.

Figure 4

(A) OS and PFS of all treated patients. (B) OS by histology. (C) PFS by histology. (D) Landmark analysis of OS based on response at 3 months after transplantation. (E) Cumulative incidence of NRM.