Repeat Treatment with Iodine-131-Rituximab Is Safe and Effective in Patients with Relapsed Indolent B-Cell Non-Hodgkin Lymphoma (NHL) Who Had Previously Responded to This Therapy.
Authors: Bishton Mark J. , Leahy Michael F. , Hicks Rod J. , Turner J. Harvey , McQuillan Ad , Seymour John Francis 
Published: October 2019

Abstract
Aims. A recent multi-center phase II trial of I131 rituximab treatment for patients (pts) with relapsed or refractory indolent B-cell NHL demonstrated an overall response rate (ORR) of 76%, with 53% attaining a complete response (CR) or CR unconfirmed (CRu). Small series suggest re-treatment with murine anti-CD20 radio-immunotherapy (Bexxarä, Zevalinä) may be safe and effective. Humanized antibodies have a longer half-life than murine antibodies, potentially prolonging bone marrow radio-isotope exposure, potentially leading to cumulative myelo-suppression on re-treatment. We therefore retrospectively analysed data from two institutions on the safety and efficacy of re-treatment with 131I-rituximab in pts with relapsed or refractory indolent CD20 positive B-cell NHL.
Methods. All pts who had been treated with two or more episodes of 131I-rituximab were identified from the institutional databases from January 2000 to July 2007. Pts received two unlabeled doses of rituximab 375mg/m2 and individualized 131-I-rituximab doses estimated to deliver a whole-body radiation absorbed dose of 0.75 Gy. Pts were monitored with weekly full blood counts until 12 wks post-therapy or recovery from nadir levels, and thyroid function was routinely monitored at follow-up visits. Following treatment, the severity and duration of cytopenias was noted, as was the development of myelodysplasia (MDS) and acute myeloid leukemia (AML), as well as elevated thyroid stimulating hormone (TSH) and/or a low free thyroxine (T4). We compared the response duration following first and second treatments and haematological toxicity.
Results. Sixteen pts [follicular (15), mantle cell (1)] who had previously responded to RIT were re-treated with I131 rituximab [median inter-treatment interval 19 months (9–54)]. There were no grade 3/4 adverse reactions during re-treatment infusion with 131I-rituximab, and in particular no anaphylaxis occurred. There was an ORR of 88%, with a 56% CR rate and by Kaplan-Meier analysis 36% of all retreated pts were estimated to be progression-free at 12 months. Six pts had longer remissions with the second treatment than their first. The time to progression post second treatment (median 11 months) was not significantly different from the first treatment (median 14 months; P=0.89). Rates of Grade 3/4 hematologic toxicity were neutropenia 29% and thrombocytopenia 27% respectively, and did not differ from first treatment (both 25%). There were no infectious complications requiring hospital admission and only one patient required packed cell transfusion. Three pts have subsequently required thyroxine supplementation, but no cases of thyroid cancer have occurred. AML was diagnosed in one pt at 28 months, although this patient had previously been treated with chlorambucil, and had a mild macrocytosis consistent with an early MDS prior to their first RIT. No cases of MDS were seen.
Conclusions. Re-treatment with 131I-rituximab is an efficacious and safe option for pts who have responded previously to 131I-rituximab. Myelo-suppression was unchanged from first exposure. Durable responses may be achieved despite modest TTP following the initial treatment.