A study at ASH 2024 found that early progression of disease in mantle cell lymphoma significantly worsens survival, indicating the need for a more nuanced approach to risk stratification.
Mantle cell lymphoma (MCL), a subtype of non-Hodgkin lymphoma, is characterized by frequent relapses and variable treatment responses, explain the authors of a recent study presented at the ASH 2024 Annual Meeting. Prior research has shown that progression of disease (POD) within 24 months is linked to poor prognosis, yet comparisons between patients with POD and those who remain progression-free (PF) have been limited, they said.
“It has been established that [POD] within 24 months in patients [with MCL] is associated with poor prognosis. However, comparisons with [PF] patients are scarce, and the cut-off at 24 months potentially oversimplifies a more complex patient trajectory,” the authors noted.
For their population-based study, the authors sought to refine the understanding of disease progression by analyzing the impact of POD timing on overall survival (OS) following first-line therapy.
The study included 1,185 patients with MCL diagnosed from 2006 to 2018 who received systemic first-line treatment. Patients were classified as experiencing POD if they had progressive disease as their best response to therapy or relapsed after an initial response. Those who had not yet met these criteria were considered PF. The analysis used Cox proportional hazards models with POD as a time-varying covariate and an illness-death model to evaluate cumulative progression risk and conditional 5-year OS.
Among the cohort, 33% received bendamustine-rituximab (BR), 30% received Nordic MCL2 (dose-escalated R-CHOP alternating with R-cytarabine followed by autologous stem cell transplantation), and 14% received R-CHOP or a similar regimen. The median age was highest for BR (75 years) and lowest for Nordic MCL2 (62 years). Nearly half of the patients (48%) experienced POD, with 12% progressing immediately after first-line therapy. The cumulative 5-year risk for POD was 44% for BR, 39% for Nordic MCL2, and 51% for R-CHOP.
POD was associated with significantly increased mortality across all treatment groups. The adjusted hazard ratio (HR) for all-cause mortality in POD versus PF patients was 7.45. Early progression (<12 months) had the most severe impact, particularly in Nordic MCL2-treated patients (HR=34.2). The 5-year OS for BR-treated patients with POD at one year was just 4.7%, compared to 50% if they remained PF. Similarly, OS was markedly reduced for early POD in Nordic MCL2 (14% vs 74%) and R-CHOP (13% vs 48%).
“Taken together, POD is associated with worse outcomes regardless of when it occurs, although very early POD is especially serious,” the authors wrote.
Even beyond 24 months, POD was associated with poor survival outcomes, underscoring the inadequacy of a fixed 24-month threshold for risk stratification.
“This underlines the importance of not limiting to a dichotomized comparison (<24/>24 months) when studying patient prognosis and eligibility for new treatments within or outside of clinical trials,” the authors noted. “The comparison of survival between patients with POD and those who remain PF incorporating the full patient pathway over a continuous timescale adds further nuance to our understanding of the disease course.”
Future research should focus on identifying factors influencing POD and OS to refine treatment strategies and enhance patient survival.
