|
Journal of Clinical Oncology, 2004 ASCO Annual Meeting Proceedings (Post-Meeting Edition).
Vol 22, No 14S (July 15 Supplement), 2004: 6732
© 2004 American Society of Clinical Oncology
The iodine I-131 tositumomab therapeutic regimen: Summary of safety in 995 patients with relapsed/refractory low grade (LG) and transformed LG non-Hodgkin's lymphoma (NHL)
S. A. Gregory,
J. P. Leonard,
S. J. Knox,
A. D. Zelenetz,
J. Armitage and
M. Kaminiski
Rush-Presbyterian-St. Luke's Medical Center, Chicago, IL; Weill Medical College of Cornell University, New York, NY; Stanford School of Medicine, Stanford University, Stanford, CA; Memorial Sloan-Kettering Cancer Center, New York, NY; University of Nebraska Medical Center, Omaha, NE; University of Michigan Comprehensive Cancer Center, Ann Arbor, MI
6732
Background: The Bexxar (tositumomab and iodine I 131 tositumomab [B]) therapeutic regimen yields high rates of complete and durable responses in pts with relapsed/refractory LG NHL. Methods: The safety of B therapy was reviewed for 995 pts with relapsed/refractory LG NHL, including 230 pts in 5 clinical trials and 765 pts in an expanded access program (EAP). Demographics and risk factors were similar for both groups except that pts from EAP were less heavily pretreated (median, 2 vs 4 prior therapies) and more frequently received Rituximab (56% vs 17%). All adverse events (AEs) occurring within 13 wks of treatment were reported, regardless of relationship to study drug. Median follow-up was 24 mo (range, 0.1 - 118 mo). Results: Most frequent hematologic (heme) AEs were grade (gr) 3/4 neutropenia (41%), thrombocytopenia (37%), and anemia (12%), requiring supportive care in 27% of pts (G-CSF, 12%; erythropoietin, 10%; platelet transfusions 12%; packed RBCs, 16%). Bleeding events occurred in 7% of pts (2% gr 3/4) and serious infection in 5%. Significant (P < .001) predictors of gr 3/4 heme toxicity were number of prior therapies, baseline blood counts, prior fludarabine, and degree of bone marrow (BM) involvement. Nonheme gr 3/4 AEs occurred in < 5% of pts. Infusions were well tolerated (2% gr 3/4 infusion AEs). Delayed toxicities included HAMA responses (cumulative incidence, 9.8% at 2 yr; 10.1% at 5 yr) and hypothyroidism (cumulative incidence, 8.7% at 2 yr; 16.6% at 5 yr), and 35 pts developed MDS/AML after B therapy. A masked independent review of BM and peripheral blood (Bennett et al. Blood. 2003;102:30a. Abstr 91) showed that the overall incidence of MDS/AML was 2.1% (95% CI = 1.3, 3.2%) with an annualized incidence of 1.1%/yr (95% CI = 0.7, 1.6%/yr). Conclusions: The most common AEs were prolonged cytopenias, but rates of heme sequelae were low. The data do not suggest an increased risk of MDS/AML over that seen in pts heavily pretreated with leukemogenic therapies. These data suggest that the risks associated with B therapy are outweighed by the clinical benefits in pts with relapsed/refractory LG NHL.
No significant financial relationships to disclose.
|
