SAN DIEGO, CA—“In patients with previously untreated, advanced follicular lymphomas (FL),” Joseph Oliver W. Press, MD, PhD, of Fred Hutchinson Cancer Research Center, Seattle, WA, states, “CHOP chemotherapy plus rituximab or CHOP chemotherapy plus 131iodine-tositumomab have produced outstanding progression-free survival (PFS) and overall survival (OS) rates.” Dr. Press presented the findings from SWOG-0016, a Phase 3, randomized, intergroup trial at the 53rd American Society of Hematology Meeting and Exposition.

Investigators conducted the study to compare PFS, OS, overall, and complete response rates, toxicities and HAMA formation between CHOP + rituximab and CHOP + 131iodine-tositumomab radioimmunotherapy (RIT). Patients (n=532) were eligible for the study if they had advanced stage (bulky stage II, III, or IV) evaluable FL of any grade (1, 2, or 3) and were treatment-naive. The CHOP-R arm of patients received six cycles of CHOP chemotherapy (cyclophosphamide 750mg/m2, doxorubicin 50mg/m2, vincristine 1.4mg/m2, and prednisone 100mg daily for five days) at 3-week intervals with six doses of rituximab anti-CD20 antibody (375mg/m2 on Days 1, 6, 48, 90, 134, and 141; following the protocol depicted by Czuczman et al [J Clin Oncol 17:268,1999]). The CHOP-RIT arm of patients received six cycles of CHOP followed by a dosimetric infusion of tositumomab/131iodine-tositumomab. One to two weeks later, CHOP-RIT patients received a therapeutic infusion of 131iodine-tositumomab labeled with sufficient I-131 (median 85 mCi) to deliver a total body dose of 75cGy to patients with normal platelet count.

The trial, conducted by the Southwest Oncology Group (SWOG) and Cancer and Leukemia Group B (CALGB), was designed to have 86% power to detect a hazard ratio (HR) of CHOP-RIT to CHOP-R of 0.67 for 2-year PFS based on a one-sided 0.021 level test.  Five hundred and twenty-six patients were evaluable for toxicity (263 in each arm) out of 554 enrolled patients. Patient characteristics, including FLIPI scores, were well-balanced in both arms.

Median follow-up among patients still living is 4.9 years. Progression or death occurred in 106/267 eligible patients receiving CHOP-R versus 86/265 eligible patients receiving CHOP-RIT.; there were 26 deaths in the CHOP-R arm and 40 deaths in the CHOP-RIT arm. The 2-year estimate of PFS was 76% for CHOP-R and 80% for CHOP-RIT, and the hazard ratio for CHOP-RIT versus CHOP-R was 0.79 (95% CI: 0.60–1.05, P=0.11 [2-sided] or P=0.06 [1-sided]). The 2-year estimate of OS was 97% of CHOP-R patients and 93% of CHOP-RIT patients, and the hazard ratio for CHOP-RIT versus CHOP-R was 1.55 (95% CI: 0.95–2.54, P=0.08 [2-sided]).

Grade ≥3 neutropenia occurred frequently in both groups. There was a trend for greater rates of infection(23%), febrile neutropenia (16%), and cardiovascular events (7%) in the CHOP-R arm, whereas thrombocytopenia (18%), thyroid dysfunction (7%), and HAMA (17%) was more prevalent in the CHOP-RIT arm. Serious adverse events did not significantly differ between groups.

Dr. Press summarized that there are presently no statistically significant differences observed for PFS, OS, or serious toxicities with either regimen. Median times to progression have not yet been achieved for either course of therapy. A follow-up trial is assessing whether CHOP-R plus RIT consolidation, along with maintenance rituximab, will be furthermore beneficial.