Efficacy of 90Y-Ibritumomab Tiuxetan in the Older Population with Non-Hodgkin Lymphoma Pre-Treated with Rituximab-Based Regimens: A Single-Institution Experience

Background: The use of (90)Y-Ibritumomab tiuxetan (90Y-IT) as radioimmunotherapy in the treatment of B-cell non-Hodgkin lymphoma (NHL) has been approved for consolidation and salvage treatment of follicular and indolent lymphoma. It has also been studied in the treatment of diffuse large B-cell and mantle cell lymphoma. Toxicities primarily include myelosuppression with a risk of treatment-associated myelodysplastic syndrome (t-MDS).

Methods: Retrospective cohort analysis of patients with B-cell NHL who received 90Y-IT from 2010 to 2016 at Geisinger Medical Center. 90Y-IT was administered as both consolidation and salvage treatment according to recommended dosing guidelines and cytopenia was monitored at routine intervals. A random subset of patients received maintenance Rituximab (R) at 375 mg/m2 every three months for eight doses.

Results: Sixty-six patients with NHL received 90Y-IT at a median age of 68 years (range 32-91), 33 (50%) patients were male, and 37 (56%) were greater than 65 years of age. Disease subtypes included: follicular center cell (n=31, 47%), diffuse large B-cell (n=22, 33%), mantle cell (n=3, 4.5%), marginal zone (n=7, 10.6%), small lymphocytic (n=1, 1.5%), and Waldenstrom macroglobulinema (n=2, 3.03%). Thirty-three patients (50.0%) had aggressive NHL and 38 (57.6%) had stage III/IV disease. Disease status prior to 90Y-IT was as follows: CR (n=33, 50%), PR (n=22, 33.3%), and relapse/refractory (n=11, 16.7%).

Twenty-nine patients (43.9%) received >1 line of treatment prior to 90Y-IT therapy. The median duration of disease prior to 90Y-IT was 18 months (range 4-184). Sixty-four patients received R prior to 90Y-IT and no patient received fludarabine-based therapy. The median PFS and OS were 27 and 30 months, respectively, for all patients. There was no significant difference in PFS and OS between patients younger and older than 65 years of age, between patients in CR and not in CR at the time of 90Y-IT, or between patients with aggressive and indolent disease.

The median follow-up period was 30 months (range 15-87). The overall response rate (ORR) was 92.4% (n=61) with a PR-to-CR conversion rate of 22.7%. In the salvage setting, the ORR was 84.8%. In the relapse/refractory setting, the ORR was 72.7%. Patients not in CR at the time of 90Y-IT were found to be responsive to R maintenance: PFS improved from median 21 to 56 months and OS improved from median 28 to 66.5 months (p=0.002).

Fifteen patients (22.7%) received R maintenance after 90Y-IT and demonstrated improvement in PFS (mean 26.9 to 49.8 months, p=0.0004) and OS (mean 32.7 to 55.7 months, p=0.0004). In the diffuse large B-cell lymphoma population, the patients with R maintenance had demonstrated benefit in PFS (mean 21.4 to 46.0 months, p=0.0423) and OS (mean 23.7 to 46.0 months, p=0.0417). Among the indolent lymphomas, the addition of R maintenance demonstrated improvement in OS from 35.4 to 57.1 months (p=0.0197).

Among patients with grade 3/4 hematologic toxicities, six (9.1%) required blood transfusion, four (6.1%) needed platelet transfusion, and 17 (25.8%) received pegfilgastrim. Two patients required hospitalization for febrile neutropenia. Ten patients (15.2%) relapsed after 90Y-IT at median 65.0 months, and one patient (1.5%) developed t-MDS (del 5q, del 20q) 54 months after treatment. There were 14 deaths (six were secondary to progressive lymphoma or chemotherapy-related neutropenic sepsis).

Conclusions: This is one of the largest single-center experiences of 90Y-IT administered to a predominantly elderly population with B-cell NHL pre-treated with Rituximab-based regimens. This study demonstrates the safety and feasibility of 90Y-IT in the elderly population with manageable toxicity, with no increased risk of treatment-related myelodysplastic events. This study also demonstrated PFS and OS benefit in administering Rituximab maintenance post 90Y-IT to both indolent and aggressive B-cell NHL and should be further investigated in future studies.