ALBERT

Description: Introduction: I-131-Tositumomab is a radiolabeled murine monoclonal antibody that binds to the CD20 antigen on the surface of malignant and normal B lymphocytes, targeting radiation to B cells. I-131-Tositumomab has been studied with chemotherapy and in high-doses as part of conditioning regimens for autologous stem cell transplant (ASCT) in relapsed/refractory B cell lymphoma patients (pts). Non-myeloablative I-131-tositumomab was approved in the US and Canada for treatment of CD20 antigen-expressing relapsed or refractory low-grade follicular or transformed non-Hodgkin lymphomas (NHL). Since February 2014, tositumomab and I-131-tositumomab, the Bexxar¨ therapeutic regimen, is no longer commercially available. Methods: We conducted a single-center, phase I trial of I-131-tositumomab in pts with CD20+ B cell NHL with relapsed or progressive lymphoma after ASCT. Eligibility criteria included creatinine grade 3 non-hematologic adverse event. After treatment, pts were monitored weekly for 13 weeks for hematological and other toxicities with response assessments at weeks 7 and 13, and then evaluated at weeks 26, 39, and 52, then every 3 months during year 2, every 4 months during year 3, every 6 months during year 4, and yearly thereafter. Results: 12 pts were enrolled and received both dosimetric and therapeutic doses of I-131-tositumomab; 6 pts (50%) were men. Median age was 58.5 years (range: 49-66). 5 of 12 (41.6%) pts had diffuse large B cell lymphoma (DLCBL), 4/12 (33.3%) follicular lymphoma (FL), and 3/12 (25.0%) FL transformed to DLBCL. Median number of prior therapies was 4 (range: 3 - 8); median time from ASCT was 1.6 years (range: 0.3 - 6.8). 2 pts had progressive disease after ASCT (1 transformed FL; 1 DLBCL); 10 pts had relapsed from complete remission (CR) after ASCT. 7 pts received 25cGy I-131-tositumomab. The cohort receiving 25cGy was expanded to 6 due to grade 4 neutropenia (1 pt), and then expanded to 7 because 1 pt progressed prior to week 7 response assessment. 3 pts received 50cGy and 1 pt each received 65cGy and 75cGy. At all doses, I-131-tositumomab was well-tolerated. Treatment-related toxicities 〉 grade 3 were exclusively hematological and not dose dependent, including thrombocytopenia (2/12: 1 grade 3, 1 grade 4), neutropenia (2/12: 1 grade 3, 1 grade 4) and anemia (2/12: 2 grade 3). Hematologic toxicities were reversible in all cases, with median time to recovery to 〈 grade 3 toxicity 7 days. Non-hematological adverse events were mild and 〈 grade 2. The most commonly reported non-hematological adverse event was fatigue. Overall response rate at week 7 was 41.6% (5/12) with 33.3% (4/12) pts achieving CR (2 pts with FL; 2 pts with DLBCL). Median duration of response was 13.8 months. As of May 2014, 2 pts are still in CR, including 1 pt with FL at 10.3 months and 1 pt with DLBCL at 5.5 years. Median progression free survival is 6.5 months; median time to treatment failure is 4.4 months. At the median follow-up of 21.9 months (range: 10.3 – 66.3), overall survival is 68.7%; no secondary hematologic malignancies have been observed. Conclusion: This is the first study of I-131-tositumomab RIT in pts with relapsed or progressive NHL after ASCT. In pts with CD20+ DLBCL, FL, or transformed FL following ASCT, non-myeloablative I-131-tositumomab is well-tolerated and can achieve sustained complete remissions. Table 1:Dose Escalation SchemaPlatelet count〉100,000, 150,000Dose level 120 cGy25 cGyDose level 240 cGy50 cGyDose level 355 cGy65 cGy Disclosures Schuster: GlaxoSmithKline: Research Funding.