Positron-emission tomography-based staging reduces the prognostic impact of early disease progression in patients with follicular lymphoma.

BACKGROUND

Previous studies reported that early progression of disease (POD) after initial therapy predicted poor overall survival (OS) in patients with follicular lymphoma (FL). Here, we investigated whether pre-treatment imaging modality had an impact on prognostic significance of POD.

METHODS

In this retrospective study, we identified 1088 patients with grade I-IIIA FL; of whom, 238 patients with stage II-IV disease were initially treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP), and 346 patients were treated with rituximab-based chemotherapy. Patients (N = 484) from the FOLL05 study served as an independent validation cohort. We risk-stratified patients based on pre-treatment radiographic imaging (positron-emission tomography [PET] versus computed tomography [CT]) and early POD status using event-defining and landmark analyses. A competing risk analysis evaluated the association between early POD and histologic transformation.

RESULTS

In the discovery cohort, patients with POD within 24 months (PFS24) of initiating R-CHOP therapy had a 5-year OS of 57.6% for CT-staged patients compared with 70.6% for PET-staged patients. In the validation cohort, the 5-year OS for patients with early POD was 53.9% and 100% in CT- and PET-staged patients, respectively. The risk of histologic transformation in patients whose disease progressed within one year of initiating therapy was higher in CT-staged patients than in PET-staged patients (16.7% versus 6.3%, respectively), which was associated with a 9.7-fold higher risk of death.

CONCLUSION

In FL, pre-treatment PET staging reduced the prognostic impact of early POD compared with CT staging. Patients with early POD and no histologic transformation have an extended OS with standard therapy.

Informations de copyright

Copyright © 2019 Elsevier Ltd. All rights reserved.

Déclaration de conflit d'intérêts

Conflict of interest statement C.L.B. reports research support from Janssen, Novartis, Epizyme, Xynomic and Bayer; reports honoraria from Dava Oncology and is a consultant for from Kite and Juno. J.F.G. is presently employed by Janssen and reports honoraria from Bayer, Epizyme, Roche, Genentech and AbbVie. P.A.H. reports research support from Portola, Molecular Templates, Incyte and J&J Pharmaceuticals and is a consultant for Portola Pharmaceutics, Celgene, Karyopharm and Juno Therapeutics. S.M.H. reports research support from ADCT Therapeutics, Aileron, Celgene, Forty Seven, Infinity/Verastem, Kyowa Hakka Kirin, Millenium/Takeda, Seattle Genetics and Trillium and is a consultant for ADCT Therapeutics, Aileron, Corvus, Forty Seven, Innate Pharma, Kyowa Hakka Kirin, Millenium/Takeda, Mundipharma, Portola and Seattle Genetics. A.K. reports research support from AbbVie, Adaptive Biotechnologies, Celgene, Pharmacyclics and Seattle Genetics and serves on the scientific advisory board for Celgene. M.J.M. reports research support from Genentech, Roche, GlaxoSmithKline, Bayer, Pharmacyclics, Janssen, Rocket Medical and Seattle Genetics; reports honoraria from Genentech, Roche, Bayer, Pharmacyclics, Janssen, Seattle Genetics and GlaxoSmithKline and is a consultant for Genentech, Bayer, Merck, Juno, Roche, Teva, Rocket Medical, Seattle Genetics, Genentech, Roche, Seattle Genetics and Bayer. A.J.M. reports research support from Incyte, Seattle Genetics, BMS and Merck and is a consultant for Kyowa Hakko Kirin Pharma, Miragen Therapeutics, Takeda Pharmaceuticals, ADC Therapeutics, Seattle Genetics, Cell Medica, Bristol-Myers Squibb and Erytech Pharma. C.H.M. reports research support from BMS, Merck and Seattle Genetics; is a consultant for AstraZeneca, BMS, Karyopharm Therapeutics, Merck, Seattle Genetics, Takeda and Vaniam Group and serves on the scientific advisory board for AstraZeneca, Karyopharm Therapeutics, Merck, Seattle Genetics, Takeda and Vaniam Group. A.N. reports research support from Pharmacyclics, NIH and Rafael Pharma and is a consultant for Janssen, Pharmacyclics, Medscape and Targeted Oncology. M.L.P. reports research support from Genentech, Juno and Regeneron; reports honoraria from Novartis, Merck, Celgene, Juno and Pharmacyclics and is not a consultant for any firms. D.S. reports research support from and serves on the scientific advisory board for Seattle Genetics. G.v.K. reports research support from Pharmacyclics, Genentech and Bayer. A.D.Z. reports research support from MEI Pharma, MorphoSys, Sandoz, Celgene, Roche and Gilead; is a consultant for Genentech/Roche, Gilead, Celgene, Janssen, Amgen, Novartis and Adaptive Biotechnology and serves on the board of directors (DMC Chair) for BeiGene. S.L. is a consultant for and serves on the scientific advisory board for Roche, Celgene, Sandoz and Gilead. M.F. reports research support from Mundipharma s.r.l., Cephalon/Teva, Celgene, Millennium/Takeda and Roche and is a consultant for and serves on the scientific advisory boards for Takeda, Roche, Celgene, Sandoz and Spectrum. A.Y. reports research support from Janssen, Curis, Merck, BMS, Syndax and Roche; reports honorarium from Janssen, AbbVie, Merck, Curis, Epizyme, Roche and Takeda and is a consultant for BioPath, Xynomic, Epizyme and Roche. F.S., A.A., A.N., K.S., L.M., V.E.S., E.J., C.O. and Z.Y. declare no conflict of interest.