Ibritumomab Tiuxetan Consolidation Following CHOP + Rituximab Improves Outcomes in Patients With Previously Untreated Diffuse Large B-Cell Lymphoma (DLBCL)

ORLANDO, Fla.—Consolidation with yttrium-90 ibritumomab tiuxetan following dose-dense cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab (CHOP-R) in patients with previously untreated diffuse large B-cell lymphoma (DLBCL) converted partial remissions (PR) to complete remissions (CR) and maintained durable responses with acceptable toxicity.

That's the conclusion of a final analysis of a phase 2 trial using dose-dense CHOP-R every 2 weeks followed by consolidation with radioimmunotherapy, Reem Karmali, MD, of Rush University Medical Center, Chicago, Ill., and colleagues reported. Dose-dense CHOP (CHOP-14), the addition of rituximab to CHOP-21, and consolidation with radioimmunotherapy following CHOP chemotherapy all have been shown to improve outcome in patients with DLBCL.

Twenty patients were enrolled in the study. Eligibility included previously untreated DLBCL with measurable disease, age >18 years, performance status 0-2, and adequate marrow, liver, and kidney function; those with transformed lymphoma were excluded. Patients received standard CHOP plus rituximab 375 mg/m2 IV on day 1, repeated every 2 weeks for 6-8 cycles, followed by consolidation with 90Y ibritumomab tiuxetan 6 to 8 weeks later, Dr. Karmali noted in a poster presentation during the 52nd American Society of Hematology Annual Meeting and Exposition.

Median age was 60 years (range, 33-81 years); 40% were male. All had ECOG performance status 0 or 1. Four patients (20%) had DLBCL stage 2; 11 (55%) stage 3; and 5 (25%) stage 4. The majority of patients had an International Prognostic Index (IPI) score of 2 (40%) or 3 (55%). Fourteen patients (70%) had extranodal disease.

Eighteen of the 20 patients completed 6 cycles of CHOP+R, 16 of whom went on to consolidation with 90Y ibritumomab tiuxetan. Of 2 patients who did not complete 6 cycles of CHOP+R, 1 patient with multiple lung masses could not tolerate further therapy, and the other withdrew consent after 5 cycles. Of 2 patients who completed 6 cycles of chemotherapy but did not receive 90Y ibritumomab tiuxetan, 1 was excluded due to abnormal biodistribution on dosimetry with the radioimmunotherapy and 1 because of organizing pneumonia.

Overall response rate (ORR) was 100% following CHOP+R alone in patients who received 4 or more cycles (n=20): 75% CR (n=15) and 25% PR (n=5). All 4 patients who stopped treatment with dose-dense CHOP+R remained in CR. With 90Y ibritumomab tiuxetan, 3 patients converted from PR to CR, maintaining an ORR of 100% (n=20), with an improved CR of 90% and PR of 10%. Estimated overall survival was 125 months; progression-free survival was 92.6 months.

The most common grade 3/4 toxicity with 90Y  ibritumomab tiuxetan was neutropenia in 8 patients (n=50%); there were no cases of neutropenic fever. At a median follow-up of 42.4 months, median progression-free survival and overall survival were not reached. Three patients relapsed (15%), all of whom had extranodal disease; 2 had an IPI of 3, and 2 had bulky disease. All relapses were retreated, with 1 patient now in CR and 2 deceased. One other patient, in CR at time of death, died of organizing pneumonia. To date, 17 patients remain alive, all in CR.

The investigators noted that chemotherapy with R-CHOP every 21 days is the standard of care for DLBCL in the front-line setting. However, the administration of R-CHOP every 14 days for dose intensification followed by 90Y ibritumomab tiuxetan consolidation for untreated DLBCL represents off-label use.

Off Label Use: Chemotherapy with R-CHOP every 21 days is the standard of care for DLBCL in the front-line setting. This study administered R-CHOP every 14 days for dose intensification followed by 90Y  ibritumomab tiuxetan (radioimmunotherapy) consolidation for untreated DLBCL.