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1143 Outcome By Primary Treatment Type and Timing of Progression Among Follicular Lymphoma Patients: A Large, Population-Based Study in Sweden

Program: Oral and Poster Abstracts
Session: 623. Mantle Cell, Follicular, and Other Indolent B-Cell Lymphoma—Clinical Studies: Poster I
Hematology Disease Topics & Pathways:
Follicular Lymphoma, Adult, Diseases, Non-Hodgkin Lymphoma, B-Cell Lymphoma, Study Population, Lymphoid Malignancies, Clinically relevant
Saturday, December 5, 2020, 7:00 AM-3:30 PM

Caroline Weibull1*, Björn E Wahlin, MD, PhD2, Sandra Lockmer3*, Gunilla Enblad4,5*, Per-Ola Andersson, MD, PhD6,7*, Eva Kimby, MD, PhD8,9 and Karin E. Smedby, MD, PhD3,10*

1Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
2Karolinska Institutet, Department of Medicine, Huddinge, and Karolinska University Hospital, Unit for Hematology, Stockholm, Sweden
3Karolinska University Hospital, Stockholm, Sweden
4Dept of Oncology, Akademiska University Hospital, Uppsala, Sweden
5Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden
6Gothenburg University, Sahlgrenska Academy, Gothenburg, Sweden
7Dept of Hematology, South Älvsborg Hospital, Borås, Sweden
8Hematology, Karolinska Institute, Stockholm, Sweden
9Karolinska Institute, Department of Medicine Huddinge and Karolinska University Hospital, Stockholm, Sweden
10Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden

Purpose: Follicular lymphoma (FL) is generally regarded as an indolent malignancy, yet the clinical outcome is highly variable. In recent years, POD24 (progression of disease within 24 months) has emerged as a potential prognostic marker for overall survival (OS) in FL and other non-Hodgkin lymphomas. The association with survival, however, has mostly been studied in selected clinical trial cohorts and among patients treated with R-CHOP. We aimed to investigate OS by timing of progression and type of primary treatment in a population-based setting in Sweden.

Methods: We identified all patients diagnosed with FL in stages II-IV and grade 1-3a between 2007 and 2014, using the population-based Swedish lymphoma register. Data were complemented with information on progression, transformation and second-line treatment through medical charts review up to December 31st, 2017. The analysis covered 4 out of 6 health care regions (75% of all patients diagnosed nationally). The patients were categorized according to type of first-line treatment: R-chemo of any type, R-Benda, R-CHOP (including R-CHOEP), or other (including immunotherapy only). Among patients where it was decided to start first-line treatment within 6 months of diagnosis (and where treatment was started within nine months), POD was defined as either lack of response to first-line therapy (stable [SD] or progressive disease [PD]), or initial response and subsequent relapse/progression/transformation as indication for second-line therapy. To quantify the impact of timing of POD on survival, the five-year OS conditional on either being progression-free (PF) or having experienced POD at different time points during follow-up, was estimated using a flexible parametric illness-death model.

Results: Among a total of 970 FL patients, median age at diagnosis was 66 years and patients were followed for a median of 6.4 years (range 0-12 years). The 5-year OS was 75% and progression-free survival was 59%. Six hundred (62%) patients had a first-line treatment within nine months of diagnosis and were hence analyzed further, whereas the remaining 370 (38%) patients were classified as wait-and-watch and were not analyzed further. Among the 600 treated patients, 337 (56%) had R-chemo (R-CHOP or alike (n=210), R-Benda (n=97), other (n=30)), and 263 (44%) received non-R-chemo treatment (mainly R-monotherapy, radiotherapy only, or R-lenalidomide). Patients who received R-Benda were on average older than the other groups. Among patients treated with R-chemo, those who stayed progression-free had a 5-year conditional OS above 75% regardless of PF time point. For patients who progressed, the 5-year conditional OS improved as time point of POD was prolonged (Fig 1a, left panel). Early POD (within 12-24 months) was associated with a particularly poor prognosis (5-year conditional OS below 55%). The OS improvement over time of POD was especially pronounced among R-Benda treated patients (Fig 1b, right panel). Among patients receiving non-R-chemo treatments, early POD was associated with a slightly worse 5-year OS but differences between POD and PF patients were less marked (Fig 1a, right panel).

Conclusion: This population-based study of Swedish stage II-IV FL patients shows that among immunochemotherapy-treated patients, progression of disease was always associated with worse survival in comparison to progression-free patients regardless of timing of progression. This reduction in survival was more pronounced the earlier the progression (as described by others). Interestingly, among patients selected for milder non-immunochemotherapy-based treatments, progression of disease did not have a strong effect on survival.

Disclosures: Weibull: Janssen Cilag: Research Funding. Wahlin: Gilead Sciences: Research Funding; Roche: Consultancy, Research Funding. Smedby: Takeda: Research Funding; Janssen: Research Funding; Celgene: Consultancy.

*signifies non-member of ASH