Timing of disease progression and impact on survival in Swedish mantle cell lymphoma patients—a novel illness‐death model study

Abstract

Background: In mantle cell lymphoma (MCL), time to relapse is a critical factor, and patients experiencing disease progression within 24 months from treatment start (POD24) have inferior survival. However, the cut-off at 24 months is arbitrary and potentially overly simplified. We aimed to quantify the impact of the timing of disease progression on overall survival, stratified by the most common first-line treatment concepts (Nordic-MCL, R-Bendamustin, and R-CHOP). Methods: Using the population-based Swedish lymphoma register, we identified all systemically treated MCL patients diagnosed between 2006 and 2018. We supplemented this with information on progression and relapse from medical chart reviews through 2022. Patients were categorized based on first-line treatment (Nordic MCL regimen, R-Bendamustin, R-CHOP, and others). POD was defined as a lack of response to primary therapy (progressive disease [PD]) or an initial response followed by a relapse. To assess the impact of POD timing on survival, we used an illness-death model with transition rates estimated using flexible parametric survival models to predict the five-year overall survival (OS) conditional on either being progression-free or experiencing POD as a smooth function of time since primary treatment. Results: A total of 1193 patients receiving systemic treatment were included. The median age at diagnosis was 70 years, and patients were followed for a median of 4 years (range 0–16 years, alive patients, six years). 33% of patients received R-Bendamustin (n = 387, median age 75 years), 30% received the Nordic MCL regimen (n = 351, median age 62 years), and 23% received R-CHOP (n = 276, median age 72 years). Almost half of the patients (48%, n = 571) experienced POD during follow-up. The five-year OS from treatment start was 47%, and progression-free survival was 32%. Among patients treated in the first line with either R-Bendamustin or the Nordic MCL protocol, those with a POD had substantially lower 5-year OS compared to patients who remained progression-free, also for POD occurring up to six years after primary treatment. For patients treated with R-CHOP, the impact of POD was largest if it occurred within 2–3 years after first-line therapy. Keyword: Aggressive B-cell non-Hodgkin lymphoma No conflicts of interests pertinent to the abstract.