PHILADELPHIA-In five clinical trials involving 250 patients with relapsed, refractory, or transformed low-grade non-Hodgkin's lymphoma (NHL), tositumomab and iodine(Drug information on iodine) I 131 tositumomab (Bexxar) produced responses of longer duration than did prior chemotherapy. The US Food and Drug Administration (FDA) Oncologic Drugs Advisory Committee recently recommended that the ra- dioimmunotherapeutic regimen be approved for the treatment of advanced NHL. The baseline demographics and disease characteristics for patients enrolled in the five clinical trials are detailed in Table 1. Reviewing longterm follow-up of these trials, Mark S. Kaminski, MD, of the University of Michigan Medical Center in Ann Arbor, reported that overall confirmed response rate was 56%, and 30% of patients achieved a complete response (see Table 2) (ASH abstract 1381).[2-5] The duration of response ranged from 10.9 to 45.4 months (median, 14.7 months). The median duration of complete response has not yet been reached, and 70% of patients who achieved a complete response were alive and still in complete response 7.8 years or longer after treatment. Dr. Kaminski concluded that tositumomab and iodine I 131 tositumomab therapy achieves durable complete responses in patients with advanced low-grade NHL. Low-Grade Transformed NHL Patients with NHL have varying response rates to chemotherapy and immunotherapy depending on the number of prior therapies and disease stage. Other studies examined responses to tositumomab and iodine I 131 tositumomab from specific patient subpopulations.[3-5] Andrew D. Zelenetz, MD, of Memorial Sloan-Kettering Cancer Center in New York, reported responses from patients with transformed low- grade NHL, a subgroup with a particularly poor prognosis and expected survival of less than 12 months (ASH abstract 1384). Among the 250 patients enrolled in the five clinical trials, 71 patients had a diagnosis of transformed low-grade NHL. These patients had received a median of four prior therapies (range, 1 to 11). The majority of patients (70%) had bulky disease (tumor size > 5 cm); 28% had bone marrow involvement; and approximately half had elevated lactate dehydrogenase and/or a modified International Prognostic Index score greater than or equal to 3. The overall confirmed response rate was 39%, and 25% of patients achieved a complete response. The median duration of response was 20 months, and the median duration of complete response was 36.5 months. Seventeen patients had a response of 12 months or more. Dr. Zelenetz concluded that the results demonstrate that tositumomab and iodine I 131 tositumomab "is an effective therapy for patients with transformed low-grade NHL." Progression After Rituximab(Drug information on rituximab) Although rituximab (Rituxan), a chimeric anti-CD20 antibody, is an effective therapy for indolent NHL, most patients eventually relapse and require further treatment. An analysis of 40 patients who failed to respond to rituximab or relapsed after treatment, found that tositumomab and iodine I 131 tositumomab produced an overall response rate of 68% and that 30% of patients achieved a complete response.[ 4] Sandra J. Horning, MD, of Stanford University Medical Center in Palo Alto, California, reported that the median duration of response was 14.7 months, and the median duration of complete response had not been reached at the time of the report (ASH abstract 1385). Nine patients were still in complete response after 12 to 26 months of follow-up. These response rates are encouraging considering that approximately two-thirds of the patients enrolled in this study had failed to respond to prior rituximab therapy, Dr. Horning noted. She concluded that the radioimmunotherapy was "highly effective in patients with indolent and transformed lymphoma" who have progressed after rituximab therapy. As Front-Line Treatment As with other treatments for NHL, it was expected that response rates to tositumomab and iodine I 131 tositumomab would be greatest in the frontline setting. This prompted a study of 76 patients with previously untreated, stage III/IV, low-grade (71% follicular small cleaved cell, 29% follicular mixed cell) NHL, and poor prognostic factors such as bone marrow involvement (63%) and elevated lactate dehydrogenase (31%). Dr. Kaminski reported that the confirmed response rate was 95%, and 74% of patients achieved a complete response. The median duration of response and the median progressionfree survival had not been reached after 8 to 66 months of follow-up. The primary toxicities associated with treatment included myelosuppression and hypothyroidism. Grade 3 or 4 neutropenia was noted in 34% of patients and grade 3 or 4 thrombocytopenia was noted in 17% of patients. Dr. Kaminski concluded that the regimen achieved a high confirmed complete response rate and had an acceptable safety profile in patients with previously untreated advancedstage NHL.