Initial report of a phase II study with R-FND followed by ibritumomab tiuxetan radioimmunotherapy and rituximab maintenance in patients with untreated high-risk follicular lymphoma

Abstract

R-FND (rituximab, fludarabine, mitoxantrone, and dexamethasone) can induce molecular remissions in indolent lymphoma. The addition of ⁹⁰yttrium ibritumomab tiuxetan (⁹⁰YIT) radioimmunotherapy following first-line induction treatment in patients with advanced follicular lymphoma (FL) may improve remission rates. We now report 10-year follow-up results from our sequential treatment approach with an abbreviated regimen of R-FND followed by ⁹⁰YIT consolidation and rituximab maintenance. Forty-nine patients were enrolled; 47 received treatment. Patients had high-risk (FLIPI score ≥3) FL of grade 1–3A and stage III/IV with adequate hematologic function. Following R-FND, the complete and partial response rates were 91% and 8.5%, respectively. After ⁹⁰YIT consolidation, the CR rate increased to 97%. The 10-year PFS rate was 49%. The most common non-hematologic, grade 3 or 4 adverse events were fatigue, dyspnea, and myalgia. Five developed myelodysplastic syndrome (MDS). This treatment approach is most appropriate in FLIPI-based high-risk patients whose outlook with standard therapy is inadequate.

Keywords:

• Fludarabine
• ibritumomab tiuxetan
• radioimmunotherapy
• B-cell lymphoma
• BCL2

Acknowledgements

For their support in bringing this project to completion, we thank the staff in the Department of Lymphoma and Myeloma at MD Anderson, including Stephanie Martch and Shayda Dioun for her assistance with writing and editing the manuscript.

Our clinical protocol was approved by the MD Anderson Institutional Review Board and supported by the National Institute of Health/NCI, Cancer Center Support Grant P30 CA16672 (PI: Dr. Peter Pisters).

This study was originally sponsored by Genentech and IDEC Pharmaceutical. Subsequently, IDEC’s role was taken over by Cell Therapeutics, and then Spectrum. Neither sponsor played a role in the design of the study; in the collection, analysis, and interpretation of the data; or in writing the manuscript.

Author contribution

PM conceived of the study; PM and BP designed the study; and NF, BP, PM, FS, SSN, MF, MAR, ET, and FBH and provided study materials or patients. FS, PM, LF, and NF participated in data analysis and interpretation, and wrote the manuscript. All authors contributed toward critical review of the manuscript and approved the final version.

Disclosure statement

FS is on the advisory board of and consults for TG Therapeutics, Astex, ADC Therapeutics, and Imbrium. SSN reports research support from Kite/Gilead, Merck, BMS, Cellectis, Poseida, Karus, Acerta, and Unum Therapeutics. He is also an advisory board member/consultant for Kite/Gilead, Merck, Celgene, Novartis, Unum Therapeutics, Pfizer, Precision Biosciences, Cell Medica, Allogene, Incyte, and Legend Biotech. MF reports research funding from Genentech; and employment (current), stock options and stock units. All other authors report no competing interests.