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2957 Yittrium 90 Ibritumomab Tiuxetan (Zevalin®) in the Treatment of Relapsed or Refractory Indolent B-Cell Non-Hodgkin Lymphoma; Integrated Analysis of Three Japanese Institution’s Experience with Improvement Trend of the Long-Term Responses over a 10 Year Study Period

Program: Oral and Poster Abstracts
Session: 623. Mantle Cell, Follicular, and Other Indolent B-Cell Lymphoma—Clinical Studies: Poster III
Hematology Disease Topics & Pathways:
Follicular Lymphoma, Diseases, Lymphoma (any), Marginal Zone Lymphoma, Non-Biological, Mantle Cell Lymphoma, Therapies, Non-Hodgkin Lymphoma, B-Cell Lymphoma, Lymphoid Malignancies
Monday, December 7, 2020, 7:00 AM-3:30 PM

Ilseung Choi, MD1*, Masaya Okada, MD2* and Tomoki Ito, MD, PhD3*

1Department of Hematology, National Hospital Organization Kyushu Cancer Center, Fukuoka-City, FKO, Japan
2Division of Hematology, Department of Internal Medicine, Hyogo College Of Medicine, nishinomiya city, Japan
31st. Department of internal medicine, Kansai Medical University, Hirakata, Japan


This study investigated all cases treated by Yittrium 90 Ibritumomab Tiuxetan (90Y-IT, Zevalin®) for relapsed or refractory indolent B-cell non-Hodgkin lymphoma at the three Japanese institutions between 2008/10/14 and 2018/5/15. 90Y-IT is the only radioimmunoconjugate agent available on the Japanese market since August 2008. J3Zi study (UMIN-CTR: 000037105) created integrated dataset of 90Y-IT treatment, and subjects were requiring at least two years follow-up period.


A total of 347 cases were registered and 316 patients of the per-protocol set were analyzed creating the integrated dataset. Overall response rate (ORR) and complete response rate (CR) were evaluated using positron emission tomography (PET, 84%), computed tomography (CT, 8%) or other methods (8%) at 8-12 weeks after 90Y-IT treatment. Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method. The prognostic factors of PFS and OS were analyzed using Cox regression analysis.


All patients had previously been administered with median of 2 (mean 3.9) chemotherapeutic regimens at a mean age of 65 years. The majority of cases were follicular lymphoma (FL) patients (75%) followed by mucosa-associated lymphoid tissue lymphoma/marginal zone lymphoma (MALT/MZL) patients (13%). The ORR was 89% and CR was 66%. The Kaplan-Meier survival curves of PFS and OS extending over the 10 year study period were shown in Figure 1A. The progression free 2-year cumulative survival rate (PFS 2-years) was 61%. The PFS 2-years of the early phase (2008/10/14-2013/7/9) defined as the cut-off date of the previous report, and the late phase (2013/7/10-2018/5/15) were 51% and 73%, respectively (p<0.0001). The overall 5-year cumulative survival rate (OS 5-years) was 77%. The OS 5-years of the early phase and the late phase were 73% and 83% respectively (p=0.0565). The evident improvement trend of the long-term responses during the 10 year study period was demonstrated (Figure 1B).

Among several prognostic factors, treatment response (CR/non-CR), number of prior treatments (≦2/≧3), sIL-2R (≦500/>500 U/ml) and progression of disease within 24 months after the first-line treatment initiation (POD24, no/yes), were the significant factors (univariate analysis, p<0.05) for both PFS and OS. The number of prior treatment and POD24 showed correlation with each other, but also showed a significant different between the early phase and the late phase of the study, thus the factors resulting in the improvement trend shown in figure 1 have to be carefully discussed.

In 316 cases, 26 (8.2%) of second primary malignancy (SPM) including 9 (2.8%) haematological malignancy (7 myelodysplastic syndrome, 1 acute myeloid leukemia and 1 chronic myeloid leukemia) were observed and 1 death (treatment related Sepsis) in 15 infection cases recorded. All the long-term follow-up safety reports were consistent with the previous studies of the relapsed/refractory low-grade follicular lymphoma, and there was no obvious trend associated with radioimmunoconjugate therapy.


The study represents the largest reported cohort for therapeutic use of 90Y-IT in Japan. The improvement trend of the long-term responses (PFS and OS) during the 10 year study period was demonstrated. The response and survival data in this large real-world cohort is superior to the previously published 90Y-IT trial data including the US phase-3 trial conducted 20 years ago. The factors resulting in this improvement trend have to be carefully assessed in attempt to achieve better outcomes for 90Y-IT treatment in future.

Figure-1 Legend

(A) Overall survival (OS, black line) and progression-free survival (PFS, gray line) with 95% confidence intervals (n=316), Kaplan-Meier method.

(B) Improvement trend of the long-term (2-year) treatment responses (PFS and OS) over the 4 periods of 90Y ibritumomab tiuxetan treatment (n=316) dated; 2008/10/14-2011/7/9 (n=91), 2011/7/10-2013/7/9 (n=86), 2013/7/10-2015/7/10 (n=60), 2015/7/10-2018/5/15 (n=79).


This study was sponsored by Mundipharma. Data management and statistical analysis under the direction of investigators Ilseung Choi, Masaya Okada and Tomoki Ito was provided by L Data Science, Co., Ltd. and was funded by Mundipharma.

Disclosures: No relevant conflicts of interest to declare.

*signifies non-member of ASH