Promising Prognostic Value of Diagnosis to Treatment Interval Among Patients With Newly Diagnosed Mantle Cell Lymphoma

Narendranath Epperla, MD, MS, The Ohio State University, Columbus, Ohio, shares findings from a pooled analysis of 3 large datasets assessing the potential significance of diagnosis to treatment interval (DTI) for the prognosis of mantle cell lymphoma (MCL), arguing that DTI should be reported among all patients with newly diagnosed MCL enrolling in clinical trials. 

Transcript: 

Hello everyone. I'm Naren Epperla from Ohio State University, United States, and I'm an assistant professor in clinical medicine. My focus is taking care of patients with lymphomas. Today, I take this opportunity to discuss a recent study [that] is looking at the impact of diagnosis to treatment interval in patients with mantle cell lymphoma. 

DTI, in short, which stands for diagnosis to treatment interval, has been shown to have prognostic relevance in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). However, similar information is not available in patients with newly diagnosed mantle cell lymphoma. Given the sparsity of data, we tried to answer this question by using 3 large data sets and doing a pooled analysis.

We included the data from [Specialized Program of Research Excellence (SPORE)] the University of Iowa and Mayo Clinic, [the Molecular Epidemiology Resource (MER)] Dataset, CALGB 50403 dataset, and the Mantle Cell Lymphoma Real World Cohort study dataset. Our question was, does the time to initiate systemic therapy impact outcomes in patients with newly diagnosed mantle cell lymphoma? 

We defined DTI, which is diagnosis to treatment interval, as the time in days from the diagnosis to initiating the therapy. We stratified the DTI groups into 2: patients who received the treatment within 14 days, [which] is a short DTI [of] 0 to 14 [days], and those who received treatment between 15 to 60 days, which is [a] long DTI. Off note, patients who are on observation and/or who received treatment beyond 60 days were not included in the analysis given the excellent outcomes associated with these patient groups, which we already know. When we did the pooled analysis, a total of 1,097 patients were included—there were more patients, but after excluding the patients with insufficient information and all the other exclusionary criteria, we landed at 1,097 patients.

Among these, 300 patients were in the short DTI group and 797 patients were in the long DTI group. First, we tried to look at the associations of DTI with adverse factors, and we noted that patients who had short DTI [were] indeed associated with some high-risk features and adverse features such as high-risk [MCL International Prognostic Index (MIPI)], that is MIPI 6.2 or higher, presence of B symptoms, bone marrow involvement, worse [eastern cooperative oncology group performance status (ECOG)] performance status which we defined as ECOG performance status of 2 or higher, and lack of receipt of intensive induction therapy. We also noted that patients with short DTI [were] also associated with high [lactate dehydrogenase (LDH)] and stage 4 disease. 

We then looked at the outcomes. Our primary endpoint was looking at overall survival and the secondary outcome was looking at progression-free survival (PFS). The median overall survival in patients who had short DTI was 7.8 years and in patients with long DTI, the median overall survival was 11.8 years. This was statistically significant between the 2 groups wherein the patients with long DTI had superior median overall survival compared to the patients who had short DTI.

This prognostic relevance for overall survival was retained even after controlling for other significant risk factors in the multivariable analysis. A similar trend was also noted for progression-free survival variants. Patients with short DTI had significantly shorter progression-free survival compared to the patients with longer DTI. Similar to the overall survival, we also noted that patients who had short DTI retained its prognostic relevance for inferior PFS on multivariable analysis after controlling for other risk factors. 

In essence, what we saw in our study was patients with short DTI had inferior outcomes and had prognostic relevance even after controlling for known risk factors, including MIPI, which is also known as mantle cell international prognostic index. Given this data, it is important to rethink our enrollment [in] clinical trials wherein we suggest that maybe patients who have aggressive disease biology could benefit from 1 cycle of treatment of the trial and then can get enrolled in the clinical trial subsequently. Thank you.

Source: 

Epperla N, Switchenko J, Bachanova V, et al; Impact of diagnosis to treatment interval in patients with newly diagnosed mantle cell lymphoma. Blood Adv 2023; 7 (11): 2287–2296. doi: 10.1182/bloodadvances.2022009225