Disease progression more than 6 years after treatment impacts overall survival in mantle cell lymphoma

Studies on mantle cell lymphoma (MCL) emphasize that patients with progression of disease (POD) ≤24 months have inferior prognosis compared to patients with later POD. This population-based study assessed the impact of POD on overall survival (OS) by timing of progression and first-line treatment. A total of 1186 MCL patients diagnosed 2006-2018 were identified in the Swedish lymphoma register. POD was defined as progressive disease after first-line treatment or relapse following initial response. Hazard ratios (HRs) with 95% confidence intervals (CIs), comparing all-cause mortality among patients with and without POD, were estimated with Cox regression. An illness-death model was used to quantify the impact of timing of progression on OS, conditional on the timepoint of POD/PF (progression-free). Patients were followed for up to 10 years following treatment (median 3.7 years). BR, Nordic MCL2, and R-CHOP/R-CHOP-like treatment were administered to 33%, 30%, and 14% of patients. Almost half (48%, n = 572) of patients experienced POD, with consequently higher mortality, regardless of timing and treatment (adjusted HR = 7.56, 95% CI: 6.32-9.05). Importantly, even for patients with POD after 6-10 years, mortality was more than two-fold increased (HR = 2.67, 95% CI: 1.05-6.79). On the absolute scale, a survival difference persisted for progression occurring up to 9 years after primary treatment. Especially early but also late progression (well beyond the 24-month mark) has a large negative impact on survival in MCL. These results highlight the need for improved first-line, including maintenance therapies to sustain remission and optimize outcomes for MCL patients.