Here is a summary of Kaminsky's presentation at ASCO, from Medscape
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Mark Kaminski[1] from the Dana Farber Cancer Institute, Boston, Massachusetts, presented data from a phase II trial of iodine-131-coupled tositumomab therapy in 76 patients who had previously untreated, stage III (30%) or IV (70%) follicular lymphoma. Median age in this group was rather young (49 years; range, 23-69), and the median time from diagnosis to protocol therapy was 8 months (1-105 months). This lag suggests that many of the patients had indolent disease, initially allowing for a "watch and wait" approach. Nonetheless, 64% of patients had marrow involvement (< 25%), and approximately 29% had high tumor burden, defined as a tumor bulk > 500 g at the time of therapy. Dosimetric amounts of tositumomab given 7-14 days prior to therapy allowed researchers to estimate the lymphoma bulk. Each patient received sufficient I-131 individually dosed to deliver 75 cGy of total body radiation.
The overall response rate was 97% (Table 1) -- impressive results which appear to be durable at a median follow-up of 16.2 months. The median duration of response has not yet been reached. Three-year progression-free survival was 71% (95% confidence interval, 56% to 83%), and estimated 3-year overall survival is 91%. Specific response data are as follows:
Table 1. Stage III and IV Follicular Lymphoma -- Response to 75cGy I-131 Delivered by Tositumomab
Number of Patients (%)
Complete response 58 (76%)
Partial response 16 (21%)
Overall response rate 74 (97%)
The t(14;18) translocation characteristic of follicular lymphoma was identified by polymerase chain reaction (PCR) during baseline analysis of the bone marrow samples from 40 study patients. In 34 of these patients (84%), posttreatment marrow samples obtained following recovery of B cells were PCR negative for the t(14;18) translocation, and remained negative at 36+ months.
Therapy with I-131 tositumomab was well tolerated. Sixty-two percent of the study patients developed human antimouse antibodies (HAMA). Two thirds of the patients developing HAMA experienced flulike symptoms beginning in the 2 weeks following therapy and lasting less than a week. Hematologic toxicity was acceptable: grade IV neutropenia occurred in only 5% of study patients, and no patients experienced grade IV thrombocytopenia. The median nadir for neutrophils was 1300 cells/mm3. Median hemoglobin nadir was 12.2 g/dL, and platelet nadir was 83,000/mm3. The nadirs generally occurred 4 to 7 weeks post-therapy.
The 16.2-month follow-up period is short, especially considering the indolent natural history of low-grade lymphoma. However, the attainment of clinical and molecular remissions in the majority of treated patients makes these early data promising. |
