LONG-TERM SURVIVAL TRENDS IN ADVANCED-STAGE MANTLE CELL LYMPHOMA: A POOLED ANALYSIS OF SIX RANDOMIZED PHASE III TRIALS FROM 1996 TO 2020

Abstract

Introduction: Mantle cell lymphoma (MCL) remains a challenging disease with a poor prognosis, despite advancements in treatment strategies. Since 1996, the German Low-Grade Lymphoma Study Group (GLSG, now German Lymphoma Alliance) and the European MCL Network have conducted six landmark randomized phase III trials—GLSG1996, GLSG2000, European MCL trial 1, MCL Younger, MCL Elderly, and TRIANGLE, which have transformed the standard of care for advanced-stage MCL patients. This study aimed to evaluate survival trends in advanced-stage MCL patients over the past three decades, focusing on the impact of evolving first-line treatments.

Methods: We performed a pooled analysis of six randomized phase III trials including treatment-naïve, advanced-stage MCL patients enrolled between 1996 and 2020. Patients were grouped into four eras (1996–2000, 2000–2004, 2004–2014, 2016–2020) based on trial enrollment periods. Overall survival (OS) was compared across eras using Kaplan-Meier methods and Cox regression models adjusted for MCL International Prognostic Index (MIPI) and treatment regimens. Additionally, we analyzed dynamic survival trends on a continuous time scale using penalized splines.

Results: Among 2541 MCL patients, survival outcomes have improved steadily since 1996. In younger patients (< 60 or ≤ 65 and suitable for high-dose treatment), median OS significantly increased from 4.9 years (5-year OS: 49%) in 1996–2000 to 6.4 years (60%) in 2000–2004, to 13.8 years (73%) in 2004–2014 and was not yet reached (84%) in 2016–2020, with nearly doubled OS in 2004–2014 (vs. 2000–2004: MIPI-adjusted HR [aHR] = 0.56, 95% CI: 0.44–0.72, p < 0.0001) and 2016–2020 (vs. 2004–2014: aHR = 0.52, 0.41–0.65, p < 0.0001) (Figure A). In older patients (> 65 or ≥ 60 and ineligible for high-dose treatment)), median OS improved albeit to a less extent from 3.8 years (5-year OS: 40%) in 1996–2000 to 4.3 years (43%) in 2000–2004, and to 4.8 years (49%) in 2004–2014, with improved OS in 2000–2004 (vs. 1996–2000: aHR = 0.70, 0.51–0.96, p = 0.025) and 2004–2014 (vs. 2000–2004: aHR = 0.80, 0.64–1.02, p = 0.070) (Figure B). In younger patients, dynamic modeling revealed a sharp decline in mortality risk between 2000 and 2005, followed by sustained improvements (Figure C). In older patients, dynamic modeling showed a constant decrease in risk from 1996 to 2014 (aHR = 0.95, 0.93–0.97, p < 0.0001) (Figure D). Patients receiving the same treatment regimens had comparable OS across different eras. Adjusting for treatment regimens eliminated most survival trends, underscoring the impact of ASCT, immunochemotherapy, rituximab maintenance, high-dose cytarabine-containing regimen, and ibrutinib on survival improvements.

Conclusions: Survival outcomes in MCL have substantially improved over the past three decades, especially in younger patients, driven largely by advancements in first-line treatments. Our findings highlight the ongoing need for treatment innovations to further enhance outcomes for MCL patients.

Encore Abstract: EHA 2025

Keywords: aggressive B-cell non-Hodgkin lymphoma

Potential sources of conflict of interest:

M. Ladetto

Consultant or advisory role: AbbVie, Acerta, Amgen, ADC Therapeutics, BeiGene, Celgene/BMS, Eusapharma, GSKI, Gentili, Gilead/Kite, Lilly, Novartis, Incyte J&J, Jazz, Regeneron, Roche, Sandoz

M. Dreyling

Consultant or advisory role: Abbvie, Astra Zeneca, AvenCell, Beigene, BMS, Genmab, Gilead/Kite, Incyte, Janssen, Lilly/Loxo, Novartis, Roche, Sobi

Honoraria: Astra Zeneca, Beigene, BMS, Gilead/Kite, Janssen, Lilly, Roche