Upfront Consolidation Combining Yttrium-90 Ibritumomab Tiuxetan and High-Dose Therapy with Stem Cell Transplantation in Poor-Risk Patients with Diffuse Large B Cell Lymphoma

Abstract

We evaluated the safety and efficacy of standard-dose yttrium-90 (Y(90)) ibritumomab tiuxetan combined with high-dose BEAM (carmustine, etoposide, cytarabine, and melphalan) after first-line induction treatment in young patients with poor prognoses diffuse large B cell lymphoma (DLBCL) (clinicaltrials.gov: NCT00689169). Seventy-five high-risk (≥2 International Prognostic Index [IPI] factors) consecutive DLBCL patients (≤65 years old) in complete remission (CR) or partial remission (PR) after rituximab chemotherapy were treated with Y(90) ibritumomab tiuxetan and BEAM regimen followed by autologous stem cell transplantation (ASCT). The median follow-up was 34 months. Of the 75 patients, 71 underwent ASCT and were eligible for analysis. Median time to reach a neutrophil count of >500/μL and platelet count of >20,000/μL was 11 days. Mucositis ≥3 (51%) occurred in most patients. Other adverse events were similar to those seen with BEAM alone. The overall response rate was 86%; 59 patients (83%) achieved a CR or unconfirmed CR. The 2-year event-free survival (EFS), overall survival (OS), and disease-free survival were 79%, 83%, and 91%, respectively. Disease status (CR/PR) and positron emission tomography (PET) findings before transplantation did not predict treatment failure. The IPI (2 versus >2) and maximum tumor diameter of ≥10 cm at diagnosis appeared to be prognosis factors for OS but not for EFS. Adding Y(90) ibritumomab tiuxetan to BEAM is safe and does not increase transplantation-related toxicity. First-line consolidation with Y(90) ibritumomab tiuxetan and high-dose chemotherapy induced high rates of EFS and OS in poor-prognosis patients with DLBCL, regardless of PET status after induction treatment and warrants a randomized study.

Pretransplant FDG‐PET in aggressive non‐Hodgkin lymphoma: systematic review and meta‐analysis

“…There was moderate risk of bias in the domain of study participation in seven studies, because six studies did not report whether refractory/relapsed disease was histologically verified and one study reported that histological verification of relapsed disease was not performed in all cases. There was moderate risk of bias in the domain of prognostic factor measurement in seven studies, because five studies did not report which PET system (stand‐alone PET or integrated PET/CT) was used, and two studies used a stand‐alone PET system instead of an integrated PET/CT system. There was high risk of bias in the domain of outcome measurement in 10 studies , because these studies did not report whether relapse after ASCT was histologically verified.…”

“…There was moderate risk of bias in the domain of prognostic factor measurement in seven studies, because five studies did not report which PET system (stand‐alone PET or integrated PET/CT) was used, and two studies used a stand‐alone PET system instead of an integrated PET/CT system. There was high risk of bias in the domain of outcome measurement in 10 studies , because these studies did not report whether relapse after ASCT was histologically verified. There was high risk of bias in the domain of study confounding in 11 studies due to several reasons.…”

“…Third, four studies mixed different histological subtypes of aggressive non‐Hodgkin lymphoma in their survival analyses. Fourth, seven studies () mixed patients who had received various induction therapies in their survival analyses. Fifth, two studies did not report at all which induction therapy was used.…”

Radioimmunotherapy (90Y-Ibritumomab Tiuxetan) for Posttransplant Lymphoproliferative Disorders After Prior Exposure to Rituximab

“…As observed in two patients, consolidation with 90 Y-IT either as a single agent or as part of high-dose intensification therapy is feasible in PTLD similarly to NHL (19,20). Finally, earlier treatment 90 Y-IT may be beneficial as observed in NHL (21).…”

Phase II Study of Yttrium-90 Ibritumomab Tiuxetan Plus High-Dose BCNU, Etoposide, Cytarabine, and Melphalan for Non-Hodgkin Lymphoma: The Role of Histology

“…20, 42–44 Consistently, 90 yttrium-ibritumomab tiuxetan has been found to have a favorable safety profile; it generally does not add toxicity to BEAM, although a trend toward increased mucositis has been noted. In a matched-cohort analysis of autologous transplant conditioning regimens for diffuse large cell lymphoma, radioimmunotherapy-based conditioning had a similar relapse incidence to TBI but with lower toxicity.…”