TY - JOUR
T1 - Phase i study of a modified regimen of 90yttrium-ibritumomab tiuxetan for relapsed or refractory follicular or transformed cd20+ non-hodgkin lymphoma
AU - Vaklavas, Christos
AU - Meredith, Ruby F.
AU - Shen, Sui
AU - Knox, Susan J.
AU - Micallef, Ivana N.
AU - Shah, Jatin J.
AU - Lobuglio, Albert F.
AU - Forero-Torres, Andres
PY - 2013
Y1 - 2013
N2 - Radioimmunotherapy capitalizes on the radiosensitivity of non-Hodgkin lymphoma (NHL) and the targeted nature of monoclonal antibodies. In an attempt to reverse bone marrow infiltration with B-cells and optimize the biodistribution of Yttrium-90 (90Y)-ibritumomab tiuxetan, we conducted a phase I study combining a single course of 90Y- ibritumomab tiuxetan after a 4-weekly course of rituximab in relapsed or refractory low-grade or transformed CD20+ B-cell NHLs with <25% marrow involvement. The 0.4 mCi/kg dose was associated with 80% grade-4 cytopenias. Dose escalation was held, and 6 patients were enrolled at a 0.3 mCi/kg cohort. As the 0.3 mCi/kg dose was well tolerated, the 0.4 mCi/kg cohort was expanded to 6 additional patients. In the expansion cohort, grade-4 cytopenia developed in 33%. Further dose escalation was held, and the maximum tolerated dose was determined at 0.4 mCi/kg. With this regimen, marrow involvement decreased in all patients with complete clearance in 50%. The overall response rate was 82%. With a median follow-up of 31.7 months, the median progression-free survival and time to next treatment were 12.3 and 10.9 months, respectively. Although this regimen was associated with a high response rate, the hematologic toxicity was higher than with the standard 90Y-ibritumomab tiuxetan regimen.
AB - Radioimmunotherapy capitalizes on the radiosensitivity of non-Hodgkin lymphoma (NHL) and the targeted nature of monoclonal antibodies. In an attempt to reverse bone marrow infiltration with B-cells and optimize the biodistribution of Yttrium-90 (90Y)-ibritumomab tiuxetan, we conducted a phase I study combining a single course of 90Y- ibritumomab tiuxetan after a 4-weekly course of rituximab in relapsed or refractory low-grade or transformed CD20+ B-cell NHLs with <25% marrow involvement. The 0.4 mCi/kg dose was associated with 80% grade-4 cytopenias. Dose escalation was held, and 6 patients were enrolled at a 0.3 mCi/kg cohort. As the 0.3 mCi/kg dose was well tolerated, the 0.4 mCi/kg cohort was expanded to 6 additional patients. In the expansion cohort, grade-4 cytopenia developed in 33%. Further dose escalation was held, and the maximum tolerated dose was determined at 0.4 mCi/kg. With this regimen, marrow involvement decreased in all patients with complete clearance in 50%. The overall response rate was 82%. With a median follow-up of 31.7 months, the median progression-free survival and time to next treatment were 12.3 and 10.9 months, respectively. Although this regimen was associated with a high response rate, the hematologic toxicity was higher than with the standard 90Y-ibritumomab tiuxetan regimen.
KW - Yttrium-ibritumomab tiuxetan
KW - immunotherapeutic approaches
KW - lymphoma and other lymphoproliferative conditions
KW - radioimmunotherapy
KW - rituximab
UR - http://www.scopus.com/inward/record.url?scp=84878844262&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84878844262&partnerID=8YFLogxK
U2 - 10.1089/cbr.2012.1387
DO - 10.1089/cbr.2012.1387
M3 - Article
C2 - 23530878
AN - SCOPUS:84878844262
SN - 1084-9785
VL - 28
SP - 370
EP - 379
JO - Cancer Biotherapy and Radiopharmaceuticals
JF - Cancer Biotherapy and Radiopharmaceuticals
IS - 5
ER -