Bendamustine/Rituximab Followed by Yttrium Y-90 Ibritumomab Tiuxetan in Previously Untreated Follicular Lymphoma

Get Permission

In the phase II Fol-BRITe study reported in Clinical Cancer Research, Lansigan et al found that a short course of bendamustine/rituximab followed by consolidation with yttrium Y-90 ibritumomab tiuxetan (Y-90 ibritumomab tiuxetan) was associated with a high response rate and a high rate of conversion of partial to complete response in patients with previously untreated follicular lymphoma.

Study Details

The U.S. multicenter study enrolled 39 evaluable patients with grade 1 to 3a, stage II to IV symptomatic or bulky follicular lymphoma between October 2010 and May 2014. Patients received rituximab 375 mg/m2 on day -7 as a lead-in to four 28-day cycles of rituximab 375 mg/m2 on day 1 and bendamustine 90 mg/m2 on days 1 and 2 of each cycle. Patients were restaged at 4 to 6 weeks after the last cycle of induction therapy, and those with at least partial response, adequate cell count recovery, and bone marrow infiltration < 25% subsequently received—at 6 to 12 weeks after induction—treatment with rituximab on day 1 and rituximab followed by infusion of Y-90 ibritumomab tiuxetan at 0.4 mCi/kg on day 8.

Overall, 82% of patients had intermediate- or high-risk Follicular Lymphoma International Prognostic Index scores and 15% had grade 3a disease.


  • After four cycles of bendamustine/rituximab, 38 (97%) of 39 patients achieved response, with 22 (56%) having CR/CRu.
  • Among 35 patients receiving Y-90 ibritumomab tiuxetan, 34 (97%) achieved response, with 31 (89%) having CR/CRu.


After four cycles of bendamustine/rituximab, 38 patients (97%) achieved response, with 22 (56%) having complete response (CR)/CR unconfirmed (CRu). Treatment with Y-90 ibritumomab tiuxetan was completed by 35 patients. Following Y-90 ibritumomab tiuxetan, 34 (97%) of 35 patients achieved response, with 31 (89%) having CR/CRu. On intent-to-treat analysis among all 39 patients, the response rate was 95%, and the CR/CRu rate was 77%. The conversion rate from partial response to CR/CRu after Y-90 ibritumomab tiuxetan was 81%. At a median follow-up of 45 months, progression-free survival was 71%. At a median follow-up of 52 months, overall survival was 96%.

Adverse Events

During bendamustine/rituximab induction, grade 3 or 4 neutropenia occurred in three patients.  During the Y-90 ibritumomab tiuxetan treatment period, grade 3 or 4 hematologic toxicities in 35 patients included neutropenia in 76%, thrombocytopenia in 74%, and anemia in 6%. During follow-up, one patient developed JC virus/progressive multifocal leukoencephalopathy (PML) at 13 months and remained alive in CR at last analysis with no further progression of PML. One patient developed chronic myeloid leukemia at 11 months and remained alive, and one patient developed acute myeloid leukemia at 15 months and remained alive.

The investigators concluded, “This report demonstrates that four cycles of [bendamustine/rituximab] followed by consolidation with Y-90 ibritumomab tiuxetan achieve high response rates that are durable. In addition, consolidation with Y-90 ibritumomab tiuxetan results in a high conversion rate of [partial response] to CR/CRu. A short course of [bendamustine/rituximab] followed by Y-90 ibritumomab tiuxetan is a safe and effective regimen for frontline treatment of [follicular lymphoma].”

Frederick Lansigan, MD, of Dartmouth-Hitchcock Medical Center, is the corresponding author for the Clinical Cancer Research article.

Disclosure: The study was funded by Teva Pharmaceutical Industries and Spectrum Pharmaceuticals. For full disclosures of the study authors, visit

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.