Long-term follow-up from the FOL-BRITe study found that following bendamustine plus rituximab (BR) treatment with Y90-ibritumomab tiuxetan (90YIT) leads to a high overall response rate (ORR) in patients with untreated follicular lymphoma (FL), according to research presented by Cristiana A. Costa, DO, from the Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center in Lebanon, New Hampshire, at the 2016 ASH Annual Meeting.
90YIT is approved for use in FL patients who achieved a complete or partial response to frontline R-CHOP chemotherapy, and Dr. Costa and researchers investigated whether 90YIT was as safe and effective when used after BR frontline therapy – which has been proven superior to R-CHOP in this setting.
Thirty-nine adult patients (median age = 57 years; range = 31-75 years) with chemotherapy-naïve FL requiring treatment were enrolled in the FOL-BRITe study from October 2010 to May 2014. All patients had stage II through IV disease and had adequate hematologic, liver, and renal function; 33 of the 39 patients (85%) had grade 1-2 disease, and six patients (15%) had grade 3a disease. According to the Follicular Lymphoma International Prognostic Index (FLIPI), 18 percent of patients had low-risk disease, 44 percent had intermediate-risk disease, and 38 percent had high-risk disease.
Treatment consisted of a short induction course of BR for four 28-day cycles, consisting of:
- rituximab 375 mg/m2 (one initial dose, then on day 1 of the next week)
- bendamustine 90 mg/m2 (administered on days 1 and 2, one week after initial rituximab dose)
If patients obtained at least a partial response (PR) after induction, had a platelet count >100,000/mm3, a granulocyte count >1,500/mm3, and bone marrow infiltration <25 percent, they then received consolidation with 90YIT six to 12 weeks after completion of the last BR cycle.
The ORR was 97 percent, with more than half of the patients (n=22; 56%) achieving a complete response (CR) or unconfirmed complete response (CRu; primary endpoint), 16 patients (41%) achieving a PR, and one patient (3%) experiencing stable disease.
Four patients were not eligible to receive consolidation with 90YIT: two due to thrombocytopenia, one due to stable disease after BR, and one who declined treatment.
Immediately following 90YIT treatment, 30 of the 35 90YIT-treated patients were in CR/CRu (86%) and four remained in PR (11%), while one patient progressed during 90YIT treatment. Dr. Costa and researchers found that 90YIT consolidation improved responses and had a high rate of conversion – some of which occurred more than one year after treatment. Most patients who were in PR after BR achieved CR/CRu immediately after 90YIT (n=10/16; 63%) and three (19%) additional patients converted to CR/CRu during follow-up.
After a median follow-up of 30 months, 25 patients (71%) remained in CR/CRu, while 10 (29%) progressed or relapsed. The 24-month progression-free survival (PFS) was 80 percent (95% CI 63-90), and the median PFS had not been reached.
Grade 3/4 hematologic toxicities that occurred during treatment with 90YIT included neutropenia (34%), leukopenia (37%), thrombocytopenia (40%), lymphopenia (15%), and anemia (6%). One patient developed John Cunningham virus /progressive multifocal leukoencephalopathy 13 months after receiving the last dose of rituximab and 90YIT.
Following treatment, secondary malignancies occurred in three patients, including one case of chronic myeloid leukemia that developed 11 months later, one case of acute myeloid leukemia that developed 15 months later, and one case of uterine cancer that developed 52 months later. One patient died due to lymphoma progression 35 months after treatment.
“BR followed by 90YIT is a well-tolerated regimen for FL with high response rates,” Dr. Costa and researchers concluded, adding that long-term safety “reflects the natural history of patients with indolent lymphomas.”
Costa CA, Zaki BI, Yen SP, et al. Short course of bendamustine and rituximab followed by 90Y-ibritumomab tiuxetan in patients with chemotherapy-naive follicular lymphoma (FOL-BRITe): Final report of response rates and progression free survival. Abstract #1793. Presented at the 2016 ASH Annual Meeting, December 5, 2016; San Diego, California.