Introduction: Yttrium90 Ibritumomab Tiuxetan (Y90-IT) is a radiolabeled anti-CD20 monoclonal antibody designed to target CD20-positive B-cell lymphoproliferative disorders. This radioimmunoconjugate combines a murine anti-CD20 antibody (ibritumomab) with the β-emitting isotope Yttrium-90 (Y90) via the chelator tiuxetan, offering dual cytotoxic mechanisms immune-mediated antibody activity and targeted radiation delivery. Y90-IT received FDA approval in 2002 for the treatment of relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin lymphoma (NHL), including in patients (pts) refractory to rituximab. Despite established efficacy in clinical trials, real-world outcomes remain underreported. This study aims to evaluate clinical outcomes, safety, and potential prognostic factors in patients treated with Y90-IT at a large academic center.

Methods: We performed a retrospective analysis of pts with low-grade B-cell NHL who received Y90-IT at Moffitt Cancer Center and were followed for up to 22 years between January 2002 and December 2024. Y90-IT was administered in accordance with the manufacturer's prescribing information and institutional protocols. Data were abstracted from institutional databases and electronic medical records. Due to the complexity of cross-institutional care, some clinical events may be underrepresented in time-to-event analyses such as Kaplan-Meier curves.

Results: A total of 122 patients with low-grade B-cell NHL were treated with Y90-IT. Among these, 72 patients (59.0%) received Y90-IT in the relapsed/refractory setting after at least one prior line of therapy, 43 pts (35.2%) received it as first-line consolidation following response to chemoimmunotherapy, and 6 pts (4.9%) received Y90-IT as first-line monotherapy. Treatment data were missing for one pt. The median age at treatment was 64 years (range, 38–89), with a slight male predominance (53.3%). Most pts had a Karnofsky Performance Status >90 (81.9%), and the majority were diagnosed with follicular lymphoma (83.6%) and had advanced-stage disease (Ann Arbor Stage III–IV, 83.5%).

The overall response rate (ORR), defined as complete response, partial response, or stable disease, was 77.9% (95% CI, 70.4–85.3); 22.1% (95% CI, 14.7–29.6) were classified as non-responders. When stratified by treatment setting, ORR was 70.8% (95% CI, 60.1–81.6) in the relapsed/refractory group, 88.4% (95% CI, 78.4–98.4) among pts treated as first-line consolidation, and 100% (95% CI, 100.0–100.0) in those who received (Y90-IT) as first-line monotherapy.

The median overall survival (OS) for the full cohort was 9.9 years (95% CI, 7.9–15.2). By treatment setting, median OS was 6.5 years (95% CI, 4.4–11.8) in the relapsed/refractory group, 15.2 years (95% CI, 11.8–not estimable [NE]) in the first-line consolidation group, and 8.4 years (95% CI, 0.6–NE) in the first-line monotherapy group. Median time to next treatment (TTNT) across all pts was 7.4 years (95% CI, 3.8–NE).

Eighteen pts (14.8%) developed secondary malignancies, with myelodysplastic syndrome or acute myeloid leukemia (MDS/AML) comprising the majority (11 pts; 64.7% of secondary malignancies). The median time from Y90-IT administration to the development of MDS/AML was 3.08 years (95% CI, 2.58–9).

Conclusions: In this large, single-institution, real-world cohort, Y90-IT demonstrated high response rates and durable survival outcomes, particularly when used as first-line consolidation in low-grade B-cell NHL. These findings reinforce its efficacy across a range of clinical scenarios. However, the observed incidence of secondary malignancies, especially MDS/AML, highlights the need for ongoing surveillance. Y90-IT production was discontinued in 2020, reflecting the shifting therapeutic landscape in B-cell lymphoid malignancies. The emergence of highly effective targeted agents and immunotherapies has significantly reduced the clinical use of radioimmunotherapy; however, our findings underscore its historical efficacy and suggest that select patient populations may still derive meaningful benefit in specific clinical contexts.

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2025
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