Timing between Rituximab and 90Y-Ibritumomab Tiuxetan in Pts with Non-Hodgkin’s Lymphoma Does Not Affect Clinical Outcomes.
Authors: Friedman Isaiah E. , Andreadis Charalambos , Diangi Yumi Taylor , Nasta Sunita D. , Luger Selina M. , Stadtmauer Edward A. , Schuster Stephen J. 
Published: April 2020

Abstract
BACKGROUND: Rituximab, a chimeric, monoclonal antibody that specifically targets CD20, is widely used in the treatment of non-Hodgkin’s lymphoma (NHL). 90Y ibritumomab tiuxetan (90Y-Iab) is the radiolabeled parent molecule of rituximab with the same antigen specificity and is currently approved for treatment of pts with relapsed or refractory low-grade, follicular, or transformed NHL. Most NHL pts in current practice are heavily exposed to rituximab (as opposed to pts in the early trials of 90Y-Iab) raising the concern for binding-site saturation translating into inferior clinical outcomes in this group. Since rituximab is detectable in the serum 6 mos after completion of treatment (Gordon et al, JCO23:1096–1102,2005), we tested the hypothesis that pts who receive 90Y-Iab within 6 mos of a standard four-week course of rituximab have inferior outcomes to pts who receive 90Y-Iab at least 6 mos after their last dose of rituximab.
METHODS: Thirty-eight pts with NHL treated with a single course of 90Y-Iab between 1999 and 2006 were included in this retrospective, single-institution study. The median age was 59 y (range 21 – 83 y) and the median number of prior therapies was 4 (range 1 – 13). Overall, 21 pts had indolent NHL (17 follicular grade 1/2, 2 small lymphocytic, and 2 marginal zone), while 17 pts had aggressive NHL (11 diffuse large cell, 3 mantle cell, 2 follicular grade 3, and 1 PTLD). Among pts, 72% had stage III/IV disease, 42% had bulky lesions (&gt;5 cm), and 58% had an elevated serum LDH. Median follow up was 17 mos (range 2 – 46 mos).
RESULTS: In this cohort, progression-free survival (PFS) was significantly shorter for pts with aggressive lymphoma, compared to pts with indolent disease (HR=2.0, 95%CI: 1.02 – 4.0, p=.044). Overall survival (OS) was also significantly decreased for pts with aggressive histology (HR=4.6, 95%CI: 1.7 – 12.9, p=.004). In our analysis, 16 pts ( 42%) received 90Y-Iab within 6 mos of their last dose of rituximab (“group A”) and 22 pts (58%) received 90Y-lab at least 6 mos after their last dose of rituximab (“group B”). Overall response rate (CR + PR) was 38% in group A (95%CI: 15 – 65%) and 50% in group B (95% CI: 28 – 72%) (p=.52). PFS was not significantly different between the study groups: 3.8 mos in group A versus 3.0 mos in group B, even when stratified by histology (HR=0.98, 95%CI: 0.48 – 2.0, p=.96). Furthermore, the median OS was 21 mos in group A and 44 mos in group B, but was not significantly different for the two groups when stratified by histology (HR=0.55, 95%CI: 0.21 – 1.4, p=.21) since there was a disproportionate number of pts with aggressive histology in group A.
CONCLUSIONS: Timing of 90Y-Iab in relation to rituximab had no effect on response rates, PFS, and OS in this retrospective analysis. To our knowledge, this is the only reported study to address this question and needs to be evaluated in additional cohorts. Given its limitations, our study suggests that treatment decisions regarding whether to administer 90Y-Iab to NHL pts should be made independent of whether rituximab was given in the previous six months.