Phase II Study of 2-Weekly CHOP+Rituximab Followed by Yttrium 90 Ibritumomab Tiuxetan (Zevalin) in Patients with Previously Untreated Diffuse Large B Cell Lymphoma (DLBCL).

Interval reduction from 3 to 2 weeks (CHOP-14; Pfreundschuh et al, Blood, 2004), addition of Rituximab to CHOP-21 (R-CHOP-21, Coiffier et al NEJM 2002) and consolidation with radioimmunotherapy following CHOP chemotherapy have all been shown to improve the outcome of DLBCL. We report the results of a Phase II clinical trial designed to evaluate the safety and efficacy of combination of the above, using 2-weekly CHOP+Rituximab followed by consolidation with Zevalin in patients with untreated DLBCL.

Patients and Methods: Patients with previously untreated DLBCL with measurable disease, age>18 years and performance status 0-2 were eligible. Patients were required to have adequate marrow, liver and kidney functions. Patients with transformed lymphoma were excluded. Patients received standard CHOP along with Rituximab 375mg/m2 IV on day 1. Treatment was repeated every two weeks for a total of 6 cycles. Zevalin was administered within 6–8 weeks after the last dose of CHOPR therapy.

Results: 14 patients were enrolled. The median age was 59.5 years (range 48–82), and 6 patients were men. All patients had an ECOG performance status of 0 or 1. 3 (21%) had stage II, 5 (36%) stage III and 6 (43%) had stage IV disease. IPI was 2 in 13 (93%) and 3 in 1 (7%). Bone marrow showed lymphoma in two patients only. LDH was elevated in 9 patients. All patients except 2 completed all 6 cycles of CHOP+R. One patient withdrew consent after 5 cycles and one patient with multiple lung masses could not be continued on therapy after two cycles because of prolonged rehab. Following CHOP+R alone in patients who received a minimum of 4 cycles of CHOP+R (13), 8 patients achieved CR and 5 achieved PR. Following consolidation with Zevalin, three patients in PR were converted to CR. After a median follow-up of 17.5 months, OSS is 14/14 (100%). 11 patients (79%) remain in CR. One patient progressed and proceeded to stem cell transplant; one came off study after 2 cycles of CHOP+R and remains with evidence of disease; and the third patient, who achieved PR with CHOP+R is waiting restaging after Zevalin. Most common adverse events were hematologic. Grade 3 Neutropenia was observed in 10 patients and grade 4 in 7. Grade 3 thrombocytopenia was observed in 3 and grade 4 in 1. Non-hematologic toxicities included: grade 3 pneumonia in 3, DVT in 1, grade 4 pneumonia in 1, grade 3 fever in 2 and grade 4 fever in 1.

Conclusion: Consolidation with Zevalin radioimmunotherapy following dose dense CHOP+R therapy is well tolerated, effective and able to convert PRs to CRs.