Conditional survival of younger patients with mantle cell lymphoma: Results from a randomized phase III trial of the European MCL Network

Abstract

During a fatal disease, patients often request updated information on their prognosis. After patients have already survived a certain time, conditional survival captures their future survival probability. We investigated conditional overall and failure-free survival in 473 younger mantle cell lymphoma (MCL) patients from a randomized phase III trial comparing immunochemotherapies R-CHOP and alternating R-CHOP/R-DHAP before autologous transplantation. Using conditional Kaplan-Meier method and Cox regression, we estimated subsequent survival of patients who had survived 1-8 years, considering MIPI, Ki-67, and treatment failure status. Starting at a lower level, R-CHOP patients only showed increasing subsequent survival as they survived longer (5-year conditional survival: 72% and 81% after surviving 1 and 7 years), while R-CHOP/R-DHAP patients had stable future survival over time (77% and 78%). The prognostic value of MIPI diminished after 3 years in R-CHOP patients but remained unchanged after R-CHOP/R-DHAP. Patients with treatment failure had markedly inferior survival compared with those in ongoing remission, regardless of the time survived. The longer patients remained in remission, the longer they would stay free of treatment failures. Our results enable personalized counselling for younger MCL patients by offering dynamic prognosis and underscore the importance of highly effective first-line treatment to improve survival.

Keywords: conditional survival; immunochemotherapy; mantle cell lymphoma; prognosis.

FIGURE 1

Kaplan–Meier plots of conditional overall survival in (A) R‐CHOP group (B) R‐DHAP group.

FIGURE 2

Kaplan–Meier estimates of 3‐ and 5‐year (A) conditional overall survival probabilities and (B) conditional failure‐free survival probabilities with 95% confidence intervals in R‐CHOP and R‐DHAP groups.

FIGURE 3

Estimates of 5‐year conditional overall survival probabilities with 95% confidence intervals from Cox regression models for (A) MIPI groups (B) treatment failure groups (C) Ki‐67 groups (N = 290) (D) MIPI and treatment failure groups in R‐CHOP group (E) MIPI and treatment failure groups in R‐DHAP group. MIPI, Mantle Cell Lymphoma International Prognostic Index.

FIGURE 4

Effects of MIPI score and treatment failure on conditional overall survival at each prediction time point in (A) R‐CHOP group (B) R‐DHAP group. MIPI, Mantle Cell Lymphoma International Prognostic Index; numbers on the left are prediction time in years from study registration; hazard ratios and corresponding 95% confidence intervals are derived from multivariate Cox regression models; the grey vertical line denotes hazard ratio of 1.