Original ResearchPositron-emission tomography–based staging reduces the prognostic impact of early disease progression in patients with follicular lymphoma
Introduction
FL is the second most common lymphoma in the United States, compromising approximately 30% of all lymphomas [1,2]. As treatment outcomes and OS continue to improve, surrogate end-points are increasingly needed to predict OS in prospective clinical trials.
Previous studies proposed early progression or an early event was the surrogate end-point predicting poor OS in patients with newly diagnosed FL. In one study, patients with FL whose disease progressed within 24 months from diagnosis (progression-free survival at 24 months [PFS24]) after treatment with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) had a 5-year OS of 50%, compared with 90% for those without early POD [3]. In a different study, patients with an event within 12 months (event-free survival at 12 months) after treatment with immunochemotherapy also had a poor OS [4]. These two studies shared similar but distinct definitions of early POD. One study based the analysis on event-free survival, which included the start of new lymphoma therapy as an event, whereas the other study used progression-free survival; therefore, early POD lacks a common definition. Nonetheless, the studies identified patients with early POD as a subgroup of patients with FL with inferior outcomes and represented an area of unmet medical needs. These observations suggested utilisation of a new clinical end-point to evaluate new treatment strategies, possibly leading to rapid approval by regulatory agencies. Furthermore, these observations suggested more intensive treatment approaches, including salvage chemoimmunotherapy followed by consolidative autologous stem cell transplantation, may be needed to improve the treatment outcome [3,5,6].
However, the imaging modality used at diagnosis and before treatment initiation in the earlier studies was not described [3,4]. Whether the prognostic significance is maintained in the PET-based staging era is currently unknown. PET with 2-[18F]-flouro-2-deoxyglucose integrated with CT (FDG-PET, hereafter referred to as PET) has emerged as an important imaging tool for staging, response assessment and predicting treatment outcomes of FL [7]. PET imaging is more sensitive than CT imaging in identifying extranodal disease and facilitates more accurate clinical staging or response assessment [[8], [9], [10], [11]]. Furthermore, several studies highlight the ability of PET imaging to identify sites of suspected transformation for targeted biopsy, which may influence the choice of initial therapy and treatment outcome [[12], [13], [14], [15]].
With this background, we examined the impact of PET staging on the treatment outcome and prognosis of FL. We also compared the prognostic significance of PFS24 after first-line therapy in patients with FL whose disease was assessed by CT or PET imaging modalities.
Section snippets
Study design
This is a retrospective study of adult patients (aged ≥18 years) diagnosed between the years of 1998 and 2009 with FL managed at Memorial Sloan Kettering Cancer Center (MSKCC). This time frame was selected to include patients who were treated in the rituximab era and to allow adequate follow-up. The institutional review board approved this study.
Participants
Patients with FL grade IIIB, composite histology or de novo disease transformation at diagnosis, with fewer than 3 clinic visits (indicative of a
Results
The median age of all 1088 patients was 57 years (range: 20–94). The median follow-up of the population was 8.3 years (range: 0.2–17.5), was 9.5 years (range: 0.3–17.5) for patients staged with CT and was 7.9 years (range: 0.2–17.2) for patients staged with PET. There was a trend of increased utilisation of PET imaging over time (Supplemental Fig. 1).
In the MSKCC cohort, patients were not evaluable if they had incomplete radiographic records (N = 57), missing treatment data (N = 1), were
Discussion
Our study provides evidence of the importance of pre-treatment PET–based staging in the current management of FL. Although early progression remains a predictor of poor outcomes in FL, the observed difference in outcomes is blunted in the era of PET-based staging. Patients who fail to achieve PFS24 and are alive at 24 months without evidence of transformation may enjoy a prolonged OS without the need for more intensive, and potentially more toxic, therapy. In the MSKCC cohort, less than 20% of
Author contributions
C.L.B., F.S., A.A. and A.Y. contributed to conception and design; C.L.B., A.A., F.S., K.S., Z.Y., S.L., L.M. and M.F. contributed to collection and assembly of data; C.L.B., A.Y., F.S., V.E.S., A.N., A.A., S.L., L.M. and M.F. contributed to data analysis and interpretation; C.L.B., F.S., A.A. and A.Y contributed to writing the first draft of the manuscript. All authors provided a critical review of the manuscript's content and approved the final manuscript. The corresponding author had full
Funding
This work was supported in part by National cancer institute (NCI) Cancer Center Support Grant (P30 CA008748). The funder of the study had no role in study design, data collection, data analysis, data interpretation or writing of the report.
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
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2022, BloodCitation Excerpt :Similarly, in the MSKCC cohort cited earlier, patients with stage I or II disease defined by PET demonstrated superior OS compared with those with stage I or II disease defined by CT. For patients with stage I disease, 10-year OS was 93% and 82%, respectively (log-rank P = .005), whereas the corresponding figures for patients with stage II disease were 89% and 68%, respectively (log-rank P = .048).15 In contrast, the clinical impact of identifying more disease sites in patients who already have evidence of AS on conventional CT- and bone marrow biopsy (BMB)–based staging is limited, with only 4% of patients upstaged from stage III to IV in one series and no effect on management.2
Treating lymphoma is now a bit EZ-er
2021, Blood AdvancesCitation Excerpt :Patients with classical indicators of more aggressive FL responded equally well to tazemetostat as those with more favorable disease. For example, patients with progression of disease within 24 months of first-line therapy (POD24) had an ORR of 63% and 25%, in the mutant and wild-type groups, respectively33 (more recent data suggest that the adverse prognosis of POD24 may be less than first estimated, with findings indicating that many patients with POD24 actually have transformed FL34,35). Double-refractory patients, to both rituximab and an alkylating agent, had ORRs of 78% and 27%, in the mutant and wild-type groups, respectively.36
The role of PET in the first-line treatment of the most common subtypes of non-Hodgkin lymphoma
2021, The Lancet HaematologyCitation Excerpt :18 (55%) of 33 patients who died after early disease progression had transformed disease, the rate of which was lower in patients staged by PET than CT. The authors hypothesised that PET staging might prevent some patients with transformation from being misdiagnosed with follicular lymphoma, which accounted for the better outcome.18 In the GALLIUM trial,17 patients were staged by CT; it is possible that patients who had rebiopsy on the basis of PET-driven identification of histological transformation might have been excluded from the GALLIUM trial.
- 1
Authors contributed equally to this work.
- 2
The Royal Marsden Hospital, London, United Kingdom.
- 3
Peking University Cancer Hospital, Beijing, China.
- 4
Sylvester Comprehensive Cancer Center, University of Miami Health System, Miami, FL, USA.
- 5
Division of Biostatistics, College of Public Health, Ohio State University, OH, USA.