A dose-escalation study of tositumomab and iodine I 131 tositumomab (Bexxar) in pts with previously treated non-Hodgkin's lymphoma (NHL) with > 25% bone marrow involvement

Abstract

6575 Introduction: The Bexxar therapeutic regimen can produce durable and complete responses in patients with relapsed/refractory low-grade NHL. Virtually all previous studies of radioimmunotherapeutic agents (including Bexxar therapy) for NHL excluded patients with extensive bone marrow involvement (BMI) with tumor (>25% intertrabecular space) due to risk of excess hematologic toxicity. Therefore, we evaluated Bexxar therapy specifically in this patient population to assess safety and toxicity in a dose-escalation study. Methods: Subjects were required to have baseline BMI of >25% and platelet count of 150,000/mm3. A patient-specific dose of Iodine 131 Tositumomab was administered to deliver a defined amount of total body radiation. Dose escalation began at a total body dose of 45 cGy (subsequently increased in increments of 10 cGy). Dose limiting toxicity (DLT) was defined as ANC < 500/mm3 or platelets <25,000/mm3 for >17 d; or ANC <750/mm3 or platelets <50,000/mm3 for >24 d. Results: Eleven patients were enrolled (8 at 45 cGy and 3 at 55 cGy). Estimated BMI was 30% to 65%, with median of approx 40%. Subjects had a median of 3 prior chemotherapies (range: 1–6). One of 6 evaluable patients treated at 45 cGy experienced hematologic DLT. Three patients (estimated BMI 40–60%) received 55 cGy, with 1 having hematologic DLT concurrent with lymphoma progression with extensive BMI. Three of 11 (27%) subjects received hematologic supportive care. Non-hematologic toxicities were minimal and were similar to previous studies. Two patients responded with durations of 1 and 43.6+ months. Conclusion: Treatment of patients with >25 % bone marrow involvement with Bexxar therapy was well tolerated at 45 cGy total body dose and can result in lymphoma responses. Further studies with additional patients and at higher doses are required to further characterize the MTD and to establish efficacy. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Corixa Corp. Corixa Corp. Corixa Corp. Corixa Corp.