90-yttrium-ibritumomab tiuxetan as first-line treatment for follicular lymphoma: updated efficacy and safety results at an extended median follow-up of 9.6 years

Abstract

Radioimmunotherapy with 90-yttrium-ibritumomab tiuxetan (90Y-IT) as first-line treatment in patients with follicular lymphoma (FL) demonstrated promising results with a complete remission (CR) rate of 56% and a median progression-free survival (PFS) of 26 months, when initially analyzed after a median follow-up of 30.6 months. The aim of this long-term follow-up was to investigate whether clinical benefits were maintained and new safety signals appeared. Fifty-nine patients, aged ≥ 50 years, with FL grade 1 to 3A in stages II to IV were treated with 90Y-IT as first-line therapy. If CR without evidence of minimal residual disease (MRD), partial response or stable disease was achieved 6 months after treatment, patients were observed without further treatment. Patients with CR but persisting MRD received consolidation therapy with rituximab. The primary endpoint was the clinical response rate. Secondary endpoints were time to progression, safety, and tolerability. After a median follow-up of 9.6 years, median PFS was 3.6 years, and 8-year PFS was 38.3%. Median overall survival (OS) was not reached during the extended follow-up, and 8-year OS amounted to 69.2%. Age 65 years and above or disease progression within 24 months of treatment were significantly associated with shorter OS. An important finding was the lack of new safety signals. In particular, no increase in secondary malignancies or transformation into aggressive lymphoma was observed compared to trials with a similar follow-up. In summary, 90Y-IT as first-line treatment demonstrates a favorable safety profile and long-term clinical activity in a substantial fraction of FL patients in need of therapy. ClinicalTrials.gov Identifier: NCT00772655.

Keywords: 90-yttrium-ibritumomab tiuxetan; 90Y-IT; First-line therapy; Follicular lymphoma.

Conflict of interest statement

K.R. has received honoraria from Roche, BMS, Amgen, Novartis, Janssen-Cilag, and Abbvie, and reports consultant/advisory roles for MSD and Essex Pharma. A.V. has received honoraria from Roche, Amgen, Kite/Gilead, Novartis, and BMS, and reports consultant/advisory roles for Roche, Amgen, Kite/Gilead, Novartis, and BMS. C.A.P. has received honoraria from BMS, Novartis, Daiichi-Sankyo, EUSA Pharma, and Sirtex Medical, and reports a consultant/advisory role for EUSA Pharma. U.K. reports consultant/advisory roles for Roche, BMS, Celgene, Novartis, Gilead, Pentixapharm, EUSA Pharma, Janssen-Cilag, AstraZeneca, Hexal, MSD, Takeda, and Amgen. C.W.S. has received honoraria from GILEAD, Janssen, Pfizer, and Roche, and reports consultant/advisory roles for BMS, Celgene, Daiichi-Sankyo, GILEAD, Hexal, Janssen, Merck Serono, Novartis, Roche, and Takeda. The other authors have no competing interests to declare that are relevant to the content of this article.

© 2022. The Author(s).

Figures

Fig. 1

Progression-free survival. a Progression-free survival after a median follow-up of 9.6 years among 59 patients treated. b Progression-free survival of patients aged 50–64 years (blue curve) as compared to patients ≥ 65 years (red curve) (P = 0.607)

Fig. 2

Overall survival. a Overall survival after a median follow-up of 9.6 years among 59 patients treated. b Overall survival of patients aged 50–64 years (blue curve) as compared to patients ≥ 65 years (red curve) (P = 0.002). c Overall survival of patients with disease progression within 24 months of 90Y-IT treatment (POD24) (red curve) as compared to patients without disease progression within 24 months (blue curve) (P = 0.004) in 47 evaluable patients

Fig. 3

Cumulative incidences. a Estimated cumulative incidence of transformation into aggressive lymphoma in 51 evaluable patients. b Estimated cumulative incidence of secondary malignancies in 55 evaluable patients. SEM, standard error of the mean