Radioimmunotherapy with I131 Tositumomab in Relapsed and Transformed Low-Grade (LG) Non-Hodgkin’s Lymphoma (NHL): Long-Term Follow-Up of a Single Institution Experience.
Authors: Qawi Huma , O’Brien Teresa M. , Venugopal Parameswaran , Shammo Jamile , Bogdanova Elena , Gregory Stephanie A. 
Published: October 2019

Abstract
Background: Tositumomab and Iodine I 131 Tositumomab (BEXXAR®) is approved for the treatment of recurrent LG or transformed CD20+ NHL refractory to Rituximab or relapsed after chemotherapy. In 5 trials and an expanded access program (>995 pts), response rates were 47%–68% (durable CRs in up to 30%) with median response durations of 12–18 months. Most pts who relapsed post-BEXXAR tolerated subsequent cytotoxic regimens, stem cell transplant, localized radiation, Rituximab, and Bexxar re-treatment.
Methods: A retrospective analysis of 49 pts with relapsed/refractory LG NHL and transformed NHL treated at Rush U. Medical Center (1998–2001) evaluated treatments pre-Bexxar, responses to BEXXAR, and treatments post-BEXXAR. All pts received BEXXAR as previously described (JCO. 19:3918). Median age was 57 yrs (range, 28–88 yrs); 88% had stage III/IV disease, and 49% had bone marrow involvement. Median time from diagnosis to Bexxar treatment was 31 mo (range, 8–204 mo); median prior treatments was 3 (range, 1–7). Prior therapies included anthracycline/ anthracenedione-based therapy in 36 (73%) pts, fludarabine in 22 (45%) pts, both in 16 (33%) pts, and Rituximab in 22 (45%) pts. Median time from last treatment failure or relapse was 3 mo (range, 1–15 mo).
Results: Overall response rate to BEXXAR was 63%, with CR in 16 (33%) pts, and PR in 15 (30%) pts. Four (8%) pts had SD. Median duration of response was 11 mo (range, 3–41 mo). Of 16 CRs, 12 (75%) were durable (TTF >12 mo). After a median follow-up of 5.3 yrs (range, 2.7–6.1 yrs), 24 (77%) of 31 responders were alive. Of the 18 nonresponders, 14 died within 1 year, and 4 pts were alive after subsequent therapy. Overall, 19 pts died from progressive disease and 2 from other causes (lung cancer and MDS/AML). Relapse After BEXXAR. 17 pts relapsed after BEXXAR and received other therapies: 11 of 12 patients who received monoclonal antibodies (Rituximab or BEXXAR) have responded and were alive at last follow up (Table 1).
Retreatment With BEXXAR. After a median follow-up of 3.4 yr since BEXXAR re-treatment, 3 pts remained in CR (2 with no further therapy); 2 were alive with disease. Interestingly, CR duration after Bexxar re-treatment compared favorably with the first Bexxar treatment in 3 pts (Table 2).
Conclusion: Radioimmunotherapy (RIT) is one of the most efficacious treatments for relapsed LG NHL and is delivered over a single week with tolerable toxicity, most of which is hematologic and reversible. Our results suggest that pts who relapse after RIT can be safely and effectively treated with various therapies and responses comparable to pts without prior RIT. We have shown that BEXXAR re-treatment may lead to significantly longer duration of remission compared to initial BEXXAR therapy.
Table 1. Relapsed Patients:Treatment After BEXXAR
Treatment Alive Dead No Further Treatment 2 0 Rituxan alone 3 0 BEXXAR 5 0 RT only 1 0 Rituximab/Chemo/RT 2 1 Rituximab/Chemo/BMT 1 0 Chemo 0 1 Chemo for Lung Ca 0 1
Table 2. Response to Retreatment With BEXXAR (All Received Fludarabine Prior to Bexxar)
Patient Response, Bexxar #1 # Treatments Response, Bexxar #2 1 CR 7 mo 0 CR 3.5 years to date 2 CR 13 mo 0 CR 3 years to date 3 CR 6 mo 1 CR 3 years, alive with disease 4 CR 12 mo 2 CR 9 mo, alive with disease 5 CR 10 mo 2 PR 3 mo, alive with disease