Evaluation of Yttrium 90 (⁹⁰Y) Ibritumomab Tiuxetan (Zevalin®) in Patients with Non-Hodgkin’s Lymphoma (NHL) Having Previously Received Autologous Stem Cell Transplant (ASCT).

Background: As the first radioimmunotherapeutic (RIT) agent approved for the treatment of relapsed or refractory B-cell NHL, yttrium 90 (⁹⁰Y) ibritumomab tiuxetan (Zevalin^®) has been shown to achieve durable responses in heavily pretreated NHL patients. In phase 1–2, the eligibility criteria for ⁹⁰Y ibritumomab tiuxetan therapy excluded patients with hypocellular bone marrow (<15%), lymphomatous involvement >25%, or prior ASCT due to concern of depleting the bone marrow reserve. However, Kaminski et al previously demonstrated that a parallel RIT agent, ¹³¹I tositumomab, was safe and efficacious when administered after ASCT (

Methods: Patients with histologically confirmed relapsed or refractory B-cell NHL, ≥18 years, platelet counts >100,000/mm³, bone marrow cellularity >15%, and lymphomatous involvement <25% were eligible for treatment. In a series of 40 patients treated with ibritumomab tiuxetan at the UPMC Cancer Center, 6 patients with prior ASCT were treated. A standard course of ibritumomab tiuxetan was given, with the therapeutic dose of ⁹⁰Y ibritumomab tiuxetan administered at 0.3 mCi/kg (the initial patient, and another with platelet count ≥150,000/mm³) or the standard dose of 0.4 mCi/kg ⁹⁰Y in the 4 remaining cases (baseline platelet count >150,000/mm³). Pretreatment diagnostic PET/CT scans were taken for all patients and evaluated for areas of lymphomatous involvement. Follow-up scans were performed approximately 12 weeks after treatment to assess patient response. Maximum toxicities were monitored weekly over a 12-week period after therapy and classified according to CTCAE v. 3.0 toxicity criteria.

Results: Patients with a prior history of ASCT had received a minimum of 4 previous regimens (range, 4–7). Subjects presented with follicular NHL (n = 3), transformed NHL (n = 1), large cell lymphoma (n = 1), and mantle cell lymphoma (n = 1). Six patients were evaluable for toxicity and 5 patients were evaluable for response. Observed toxicities were consistent with those expected in this patient population, with 33% (2/6) and 17% (1/6) of patients experiencing grade 4 thrombocytopenia and grade 3 neutropenia, respectively. Episodes of bleeding or neutropenic fever were not observed. Of the 5 patients evaluable for response, 1 patient with follicular lymphoma had a complete response to ibritumomab tiuxetan as determined by FDG-PET imaging.

Conclusions: Ibritumomab tiuxetan therapy is feasible and safe in NHL patients who have previously received ASCT. Heavily pretreated patients can benefit from the administration of ibritumomab tiuxetan although additional data are needed to further characterize the degree of clinical response after ASCT.