Survival by First-line Treatment Type and Timing of Progression Among Follicular Lymphoma Patients: A National Population-based Study in Sweden

Caroline E Weibull; Tove Wästerlid; Björn Engelbrekt Wahlin; Per-Ola Andersson; Sara Ekberg; Sandra Lockmer; Gunilla Enblad; Michael J Crowther; Eva Kimby; Karin E Smedby

doi:10.1097/HS9.0000000000000838

Survival by First-line Treatment Type and Timing of Progression Among Follicular Lymphoma Patients: A National Population-based Study in Sweden

Hemasphere. 2023 Feb 23;7(3):e838. doi: 10.1097/HS9.0000000000000838. eCollection 2023 Mar.

Authors

Caroline E Weibull¹, Tove Wästerlid^{1

2}, Björn Engelbrekt Wahlin^{2

3}, Per-Ola Andersson⁴, Sara Ekberg¹, Sandra Lockmer^{2

3}, Gunilla Enblad⁵, Michael J Crowther^{6

7}, Eva Kimby³, Karin E Smedby^{1

2}

Affiliations

¹ Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
² Department of Hematology, Karolinska University Hospital, Stockholm, Sweden.
³ Unit of Hematology, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.
⁴ Section for Hematology and Coagulation, Sahlgrenska University Hospital, Gothenburg, Sweden.
⁵ Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology, Uppsala University, Uppsala, Sweden.
⁶ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
⁷ Red Door Analytics, Stockholm, Sweden.

Abstract

In follicular lymphoma (FL), progression of disease ≤24 months (POD24) has emerged as an important prognostic marker for overall survival (OS). We aimed to investigate survival more broadly by timing of progression and treatment in a national population-based setting. We identified 948 stage II-IV indolent FL patients in the Swedish Lymphoma Register diagnosed 2007-2014 who received first-line systemic therapy, followed through 2020. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated by first POD at any time during follow-up using Cox regression. OS was predicted by POD using an illness-death model. During a median follow-up of 6.1 years (IQR: 3.5-8.4), 414 patients experienced POD (44%), of which 270 (65%) occurred ≤24 months. POD was represented by a transformation in 15% of cases. Compared to progression-free patients, POD increased all-cause mortality across treatments, but less so among patients treated with rituximab(R)-single (HR = 4.54, 95% CI: 2.76-7.47) than R-chemotherapy (HR = 8.17, 95% CI: 6.09-10.94). The effect of POD was similar following R-CHOP (HR = 8.97, 95% CI: 6.14-13.10) and BR (HR = 10.29, 95% CI: 5.60-18.91). The negative impact of POD on survival remained for progressions up to 5 years after R-chemotherapy, but was restricted to 2 years after R-single. After R-chemotherapy, the 5-year OS conditional on POD occurring at 12, 24, and 60 months was 34%, 46%, and 57% respectively, versus 78%, 82%, and 83% if progression-free. To conclude, POD before but also beyond 24 months is associated with worse survival, illustrating the need for individualized management for optimal care of FL patients.