Impact of diagnosis to treatment interval in patients with newly diagnosed mantle cell lymphoma

Abstract

The prognostic relevance of diagnosis to treatment interval (DTI) in patients with newly diagnosed mantle cell lymphoma (MCL) is unknown. Hence, we sought to evaluate the impact of DTI on outcomes in MCL using three large datasets: (1) the University of Iowa/Mayo Clinic Specialized Program of Research Excellence MER, (2) patients enrolled in the ALLIANCE/CALGB 50403, and (3) a multi-site MCL patient cohort. Patients were a priori divided into two groups, 0-14 days (short DTI) and 15-60 days (long DTI). The patients in whom observation was deemed appropriate were excluded. 1097 patients with newly diagnosed MCL and available DTI were included in the study. 27% (n=300) had short DTI, while 73% (n=797) had long DTI. Patients with short DTI had worse ECOG performance status (ECOG PS ≥2, 14%vs4%, p<0.01), stage IV disease (91% vs 84%, p=0.009), higher lactate dehydrogenase (50%vs36%, p<0.01), bone marrow involvement (89%vs81%, p=0.005), more frequent B symptoms (35%vs28%, p=0.02), higher MIPI (MIPI ≥6.2, 44%vs24%; p<0.001), and were less likely to receive intensive induction therapy (64%vs53%, p=0.001) compared to long DTI group. The median PFS (2.5 years vs. 4.8 years, p<0.0001) and OS (7.8 years vs. 11.8 years, p<0.0001) were significantly inferior in the short DTI group compared to the long DTI cohort and remained significant for PFS (HR=1.50; 95%CI=1.20-1.87) and OS (HR=1.57; 95%CI=1.20-2.06) in multivariable analysis. We show that the DTI is an important prognostic factor in patients with newly diagnosed MCL and is strongly associated with adverse clinical factors and poor outcomes. DTI should be reported in all the newly diagnosed MCL patients who are enrolling in clinical trials and steps must be taken to ensure selection bias is avoided.