High Response Rates and Durable Remissions in Patients with Previously Untreated Advanced-Stage Follicular Lymphoma Treated with Tositumomab and Iodine I-131 Tositumomab (Bexxar)
Reviewer: Walter Sall, MD
Last Modified: December 7, 2002
Presenter: Mark S. Kaminski
Presenter's Affiliation: University of Michigan
Type of Session: Poster
- I-131 Tositumomab is a monoclonal murine antibody directed against the CD20 cell surface protein present on most lymphocytes, including most lymphoma cells.
- Recent trials of Bexxar in patients with relapsed or refractory low grade non-Hodgkin's lymphoma (LG NHL) have shown that sustained, durable remissions up to 8+ years are possible.
- Bexxar is likely to be more effective as first line therapy as treatment naive patients have a more intact immune system and less chance of treatment resistant disease.
- This prompted a trial of Bexxar in previously untreated stage III/IV patients with LG NHL.
Materials and Methods
- Phase II single center study. Patients enrolled from June 1996 to April 1999. Median F/U 43 months .
- Median age 49 years. All patients were stage III or IV, never previously treated. 71% were small cleaved cell while 29% were follicular mixed cellularity. 63% had positive bone marrow and 31% had elevated LDH.
- Bexxar was administered according to the standard protocol as previously described by Kaminski. Briefly, an initial dosmetric dose of 5 mCi was administered in order to determine the therapeutic dose required to provide a total body dose of 75 cGy. This dose was delivered in a single administration.
- 95% overall response rate. 74% Complete response rate (CR). 79% of complete responders still in CR after 30-66 months.
- 5 year progression free survival (PFS): 62.3%. Median duration of response and median PFS not yet reached.
- 94% of patients PCR (+) for the t(14;18) translocation at enrollment became PCR negative after treatment.
- Primary side effect was myelosupression. Median neutrophil nadir was 1,300; median platelet nadir was 83,000. No patients required transfusion or growth factor support
- Hypothyroidism was the other main toxicity. Estimated 4 year incidence of hypothyroidism was 12%.
- 63% of patients developed human anti-murine antibodies, possibly limiting future retreatment with Bexxar. This is significantly higher than the 10% rate seen previously in trials of patients with relapsed or refractory LG NHL.
- No incidence of myelodysplastic syndrome at median follow-up of 2.6 years.
- Bexxar provides a high CR rate (74%) in previously untreated advanced stage follicular NHL.
- Bone marrow and thyroid toxicity is acceptably low.
- The initial treatment of low grade lymphoma remains controversial. The data presented in this trial provide support for the use of molecularly targeted therapies such as Bexxar in the first line treatment for LG NHL. Bexxar leads to a high response rate in treatment naive patients with a low incidence of associated side effects, especially when compared to conventional cytotoxic chemotherapy. Phase III trials are necessary in order to further define the utility of Bexxar as first line therapy and to clarify the significance of the rather high incidence of human anti-murine antibody production, which may limit the potential of Bexxar retreatment.
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