Treatment de-escalation in good-risk diffuse large B-cell lymphoma: A population-based study from the Netherlands and Sweden

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Diana Al-Sarayfi (1), Mirian Brink (2), Wouter Plattel (1), Ingrid Glimelius (3,4), Karin Smedby (4,5), Sandra Eloranta (4), Marcel Nijland (1)

(1) University Medical Center Groningen, Department of Hematology, Groningen, (2) Netherlands Comprehensive Cancer Organisation (IKNL), Department of Research and Development, Utrecht, (3) Uppsala University, Department of Immunology, Genetics and Pathology, Cancer Precision Medicine, Uppsala, (4) Karolinska Institutet, Department of Medicine Solna, Clinical Epidemiology Division, Stockholm, (5) Karolinska University Hospital, Department of Hematology, Stockholm

No potential conflicts of interest

Introduction

Prospective trials (FLYER, S1001) demonstrated that four cycles of R-CHOP are non-inferior to six cycles in patients with good-risk limited stage diffuse large B-cell lymphoma (LS-DLBCL). Whether these de-escalation strategies are implemented in clinical practice and are reproducable in a broader, real-world population is unknown.

Methods

We included patients ≥18 years with Ann Arbor stage I–II, non-bulky diffuse large B-cell lymphoma (DLBCL) diagnosed between 2019–2023 in the Netherlands and Sweden, who received ≥3 cycles R-CHOP. Patients receiving 3 cycles without radiotherapy, R-miniCHOP, or R-CEOP were excluded. Treatment was categorized as 6 R-CHOP, 3 R-CHOP plus radiotherapy (RT) or 4 R-CHOP. Main outcomes were progression-free survival (PFS), overall survival (OS) and relative survival (RS). To estimate risk on relapse and mortality, multivariable analyses were used and adjusted for age, sex, Ann Arbor stage, LDH, and performance status.

Results

Out of a total population of 10,895 DLBCL patients, 1,856 (17%) were included (median age 67 years; 66% from the Netherlands), with median follow-up of 40 months. Treatment consisted of 6 R-CHOP (63%), 3 R-CHOP+RT (19%), or 4 R-CHOP (18%). Implementation rate of 4 R-CHOP was 17% in the Netherlands and 18% in Sweden. Overall response rates were similar between modalities (p=0.20). The 3-year PFS and OS for the total cohort were 86% and 90%, respectively. By treatment, the 3-year PFS was 83% for 6 R-CHOP, 94% for 3 R-CHOP + RT and 89% for 4 R-CHOP (p<0.01). The 3-year OS was 89%, 93%, and 94%, respectively (p<0.01). The 3-year RS was 94% for 6 R-CHOP, 100% for 3 R-CHOP + RT and 98% for 4 R-CHOP. After adjustment, risk of relapse and risk of mortality was similar between 4 R-CHOP and 6 R-CHOP (hazard ratio (HR) 1.00, 95% CI 0.65–1.55, and HR 0.97, 95% CI 0.58–1.64, respectively). In contrast, 3 R-CHOP+RT was associated with reduced relapse risk compared to 6 R-CHOP (HR 0.53, 95% CI 0.32–0.88) without OS-advantage (Figure 1).

Conclusion

This population-based study shows that 4 R-CHOP achieves comparable outcomes to 6 cycles in good-risk LS-DLBCL, supporting de-escalation strategies in clinical practice. Moreover, at 3-year follow-up 3 R-CHOP plus radiotherapy was associated with improved disease control.

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