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
Authors: Karmali Reem , Manson Andrew , Bueschel Katherine , Shell Kathryn , Gregory Stephanie A. , O'Brien Teresa , Shammo Jamile M. , Larson Melissa L , Venugopal Parmeswaran 
Published: October 2019

Abstract
Abstract 3947

Background:
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 and Methods:
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.

Results:
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.

Conclusion:
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.

Disclosures:
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.