90Y-Ibtritumomab as a Single Agent for De Novo or Transformed Diffuse Large B Cell Lymphoma.

BACKGROUND: 90Y-Ibritumomab is approved for use in relapsed/refractory follicular non-Hodgkin’s lymphoma (NHL), and for transformed lymphoma. It is also being studied in the setting of relapsed diffuse large B cell lymphoma.

AIM: To determine response rate and duration, and toxicity of 90Y-ibritumomab in relapsed/refractory diffuse large B-cell (de novo or transformed) lymphoma (DLBCL).

METHODS: Permission for the study was obtained from the Institutional Review Boards of St. Francis Hospital and Harford Hospital, Hartford, CT, respectively. Patients who had received 90Y-ibritumomab for DLBCL were identified. A retrospective chart review was conducted to determine patient and disease characteristics, safety and efficacy of 90Y-ibritumomab.

RESULTS: A total of 9 individuals received 90Y-ibritumomab between May, 2004, and November, 2006. Their median age was 71 years (48–90 years) and male:female ratio 4:5. Pathology at initial diagnosis was de novo DLBCL (n=4), and follicular (n=4) or small B cell NHL (n=1). The interval to transformation to DLBCL in the latter 5 patients was a median of 7 years (0.5–10 years). At original diagnosis, 5 patients had B symptoms, 3 had bone marrow involvement, 5 had CD10-positivity, 6 had intermediate high or high risk features, and only one had a cytogenetic abnormality (t14;18;22).The median number of prior treatment regimens was 2 (1–3). Seven had received radiation. The last dose of rituximab was administered a median of 9 months (1 week-18 months) previously. Patients were refractory to (n=4) or relapsed after (n=5) the last treatment (chemotherapy and/or rituximab). The median duration of response to last treatment was 2.5 months (1–12 months). The interval from diagnosis of de novo or transformed DLBCL to treatment with 90Y-ibritumomab was a median of 12.5 months (6–35 months). At the time of treatment with 90Y-ibtitumomab, 3 patients had B symptoms, and 4 had <25% bone marrow involvement. The risk status at the time of treatment with ibritumomab was low (n=1), low intermediate (n=2), high intermediate (n=1), and high (n=3) where information was available. There were no non-hematologic or infectious adverse events. The median duration of an absolute neutrophil count <1.5 x 10⁹/L was 4 weeks (0–12 weeks), hemoglobin <10 g/dL 4 weeks (0–12 weeks), and platelet count <100 x 10⁹/L 6 weeks (4–12 weeks). Two patients required platelet and red cell transfusion support. The complete and partial response rates were 11% and 11%, respectively. The duration of response in these 2 patients was 24 months (on-going) and 3 months, respectively. The median progression-free and over-all survival following 90Y-ibritumomab was 3 months and 12 months, respectively. The only patient (de novo DLBCL) who achieved a complete response remains disease-free at this time. She had failed two prior chemotherapy regimens combined with rituximab and was not eligible for stem cell transplantation.

CONCLUSIONS: 90Y - ibritumomab is well tolerated in patients with relapsed/refractory DLBCL but response rates are low and response durations short. Outcome was poor whether or not patients had de novo or transformed DLBCL. 90Y-Ibritumomab cannot be recommended as a single agent in relapsed/refractory patients with DLBCL.