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): Final Analysis

Dose dense CHOP (CHOP-14), the addition of rituximab to CHOP-21 and consolidation with radioimmunotherapy following CHOP chemotherapy have all been shown to improve the outcome of DLBCL. We report the results of final analysis of a phase II clinical trial using a combination of the above with dose dense CHOP+R, every 2 weeks, followed by radioimmunotherapy consolidation in untreated DLBCL patients.

Patients with previously untreated DLBCL with measurable disease, age >18 years, performance status 0–2, and adequate marrow, liver and kidney function were eligible. Those with transformed lymphoma were excluded. Patients received standard CHOP along with rituximab 375mg/m2 IV on day 1, repeated every two weeks for 6 cycles, followed by Zevalin consolidation 6–8 weeks later.

20 patients were enrolled. The median age was 60 years (range 33–81 years). 8 patients were men and all patients had an ECOG performance status of 0 or 1. 4 (20%) had stage II, 11 (55%) stage III and 5 (25%) stage IV disease. The majority of patients had an IPI of 2 (40%) or 3 (55%). 14 patients (70%) had extra-nodal disease. 18 patients completed 6 cycles of CHOP+R, 16 of whom went onto Zevalin consolidation. Of the 2 patients who did not complete 6 cycles of CHOP+R, one patient with multiple lung masses could not tolerate further therapy and the other withdrew consent after 5 cycles. Of the 2 patients who completed 6 cycles of chemotherapy but did not receive Zevalin, one was excluded due to abnormal biodistribution on dosimetry with Zevalin and the other because of organizing pneumonia. Following CHOP+R alone in patients who received 4 or more cycles (n=20), ORR was 100% with a 75% CR (n=15) and a 25% PR (n=5). All 4 patients who stopped treatment with dose dense CHOP+R remained in CR. With Zevalin, 3 patients converted from PR to CR, maintaining an ORR of 100% (n=20) with an improved CR of 90% and a PR of 10%. The most common grade 3/4 toxicity with Zevalin was neutropenia in 8 patients (n=50%) with no cases of neutropenic fever. At a median follow-up of 42.4 months, median PFS and OS were not reached. 3 patients relapsed (15%), all of whom had extra-nodal disease, 2 had an IPI of 3, and 2 had bulky disease. All relapses were retreated with one patient now in CR and 2 deceased. One other patient died of organizing pneumonia, in CR at the time of death. To date, 17 patients remain alive, all in CR.

Consolidation with Zevalin radioimmunotherapy following dose dense CHOP+R therapy converts PRs to CRs and maintains durable responses with acceptable toxicity in patients with untreated DLBCL.

Off Label Use: Chemotherapy with R-CHOP every 21 days is the standard of care for DLBCL in the front-line setting. We are administering R-CHOP every 14 days for dose intensification followed by zevalin (radioimmunotherapy) consolidation for untreated DLBCL. This regimen is off-label. Gregory:Amgen: Consultancy; Astellas: Research Funding; Celgene: Research Funding; Cephalon: Research Funding, Speakers Bureau; Genentech (Roche): Consultancy, Research Funding, Speakers Bureau; Glaxo-Smith-Kline: Research Funding; Immunomedics: Research Funding; NCIC CTG: Research Funding; Novartis: Consultancy, Research Funding; Onyx (Proteolix): Research Funding; Spectrum Pharmaceuticals: Consultancy.