⁹⁰Y Ibritumomab Tiuxetan (Y2B8, Zevalin®) Radioimmunotherap (RIT) Is Highly Effective for Relapsed or Refractory Indolent B-Cell Non-Hodgkin’s Lymphoma (B-NHL) Pretreated with Rituximab-Containing Chemotherapy (R-Chemo): Japanese Multicenter Phase II Study.

Background and Objectives: Y2B8 RIT has been reported to be effective in patients with relapsed or refractory indolent B-NHL pretreated with rituximab monotherapy or chemotherapy. However, no data has been available for Y2B8 in indolent B-NHL pretreated with R-chemo. We conducted a multicenter phase II study of Y2B8 RIT to evaluate its efficacy and safety in patients with relapsed or refractory indolent B-NHL, focusing on those pretreated with R-chemo.

Patients and Treatment: The Y2B8 regimen comprised an infusion of rituximab (250 mg/m²) and injection of ¹¹¹In ibritumomab tiuxetan (In2B8) (3.5 mCi [129.5 MBq]) for imaging interpretation and estimation of the feasibility of Y2B8 administration, followed 1 week later by rituximab (250 mg/m²) and Y2B8 (0.4 mCi [14.8 MBq/kg] for platelets >150,000/μL or 0.3 mCi/kg [11.1MBq/kg] for 100,000/μL< platelets <150,000/μL). A total of 45 patients (32–72 years; median, 57 years) were enrolled: 66.7%, of stage III/IV at study entry; 82.2%, with follicular lymphoma; 33.3%, with bone marrow involvement; and 55.6%, with more than 2 prior therapy regimens (range, 1–11). Of them, 40 patients were treated with Y2B8: 22 with 0.4 mCi/kg and 18 with 0.3 mCi/kg. Two patients showed prominent bone marrow uptake on imaging inspection and did not receive Y2B8. Twenty-two patients were previously treated with R-chemo (18 R-CHOP, 2 R-COPP, 2 CHASER, 1 R-FAMP, and 1 R-EPOCH) and 15 patients had received rituximab monotherapy. Only 5 patients had not received rituximab.

Results: The overall response rate was 83% (63% complete response [CR], 5% complete response unconfirmed [CRu], and 15% partial response [PR]), as evaluated by International Workshop Criteria modified by Japan Clinical Oncology Group. %CR in patients pretreated with R-chemo was 73% (78% in pts pretreated with R-CHOP). The median progression-free survival (PFS) time was 9.6 months (95% CI: 7.3 months to not calculated) with a median follow-up time of 6.5 months (range: 1.2–12.7 months). In complete responders, the median PFS has not been reached. Toxicity was primarily hematologic, transient, and reversible except in 2 patients, in whom prolonged grade 3 cytopenia and anemia did not recover by 6 months after the therapy (neutropenia and decreased Hb in one and thrombocytopenia in another). The incidence of grade 4 neutropenia, thrombocytopenia, and anemia was 43%, 5%, and 5%, respectively. No grade 4 non-hematologic toxicity was observed. Most frequent grade 3 non-hematologic toxicities were febrile neutropenia (4%), cystitis (4%), and pneumonia (4%).

Conclusions: Y2B8 RIT is highly effective with acceptable toxicities in patients with relapsed or refractory indolent B-NHL. It is noteworthy that Y2B8 RIT brings high %CR in patients pretreated with R-chemo such as R-CHOP therapy.