Time to Relapse May Predict Long-Term Outcomes in Mantle Cell Lymphoma

Peter Riedell, MD

Despite autologous hematopoietic cell transplantation (autoHCT), many patients with mantle cell lymphoma (MCL) relapse. However, time to relapse may provide clues for a patient’s long-term outcome.

An analysis of patients diagnosed with MCL treated with rituximab (Rituxan)-based induction therapy followed by first autoHCT within 1 year of diagnosis aimed to determine if the length of time until relapse effected long-term outcomes. Data between 2008 to 2018 was collected using the Center for International Blood and Marrow Transplant Research (CIBMTR) database.

In total, 461 patients were included in the analysis, with the median age being 60 years. Among the patients, 57% had a Karnofsky Performance Score of 90 or greater and 83% had stage III to IV disease at diagnosis. Additionally, 76% had extra nodal involvement. At the median follow-up of 67 months, the 5-year progression-free survival was 45.8% and the 5-year overall survival (OS) was 69.6%.

In an interview with Targeted Oncology, Peter Riedell, MD, an assistant professor of Medicine at the University of Chicago, discussed the analysis and its results in more detail. He also explained what the study findings mean for clinical practice.

TARGETED ONCOLOGY: What are outcomes generally like for patients with MCL? How does timing of relapse following transplant impact OS?

Riedell: Mantle cell lymphoma is an uncommon subtype of B-cell non-Hodgkin lymphoma, and overall, outcomes can be very heterogeneous. In young and fit patients, 1 of the standard treatment paradigms would be utilization of upfront rituximab and cytarabine-containing induction regimen followed by consolidative autologous stem cell transplant. And in general, the outcomes are favorable with that treatment approach. In our study, we demonstrated findings including a 5-year progression-free survival of close to about 45%, with a 5-year overall survival close to about 70%. One of the things to note though, is there is a population of patients that do relapse early, and we specifically wanted to focus on that population of patients to evaluate their outcomes, and the impact of early relapse in that population of patients undergoing an upfront transplant. Through a dynamic landmark we were able to look at relapse at different time points, and we specifically noted in our analysis that patients that relapse by the 6-, 12-, and 18-month landmark time points following auto transplant had very poor outcomes overall.

Can you go into some background about the study design and what methods were used to conduct this analysis?

This analysis was conducted using the CIBMTR database and we essentially were evaluating population of patients that underwent an upfront autologous stem cell transplant. All the patients were diagnosed andunderwent transplant within 12 months of diagnosis of mantle cell lymphoma, and that was used as a point in time in order to essentially attempt to capture a more homogenous population of patients and those patients that typically require treatment at the time of diagnosis, compared to the minority of patients with MCL who may be managed with a watch-and-wait approach. Within that population, we used a dynamic landmark analysis, which was performed at 6-month intervals spanning 5 years following transplant, in order to evaluate the impact of time to relapse on overall survival. Additionally, we were able to adjust for significant patient and disease-related variables.

Can you go into some more detail about the findings? And then what are the implications of these findings?

One of the big findings that we noted is that the time to relapse after autologous stem cell transplant does have a significant impact on patients’ overall survival, and not surprising, those patients that relapse early do poorly. Through our analysis, we were able to determine an optimal cut point of where the overall survival was more favorable for a population of patients and less favorable for the other minority of patients. And that time point was 18 months. Essentially, if patients relapse after 18 months, their survival and their long-term outlook was certainly more promising than patients who relapse less than 18 months. Where I think this data really translates to and informs our practices is in the fact that that we need 2 things. One is to better identify which patients are the ones that relapse early as it is these patients where we need to be able to potentially incorporate different induction regimens, or more so, regimens at the time of relapse including clinical trials and utilization of novel agents.. Similarly, patients that relapse later may potentially benefit from some of our traditional therapies like BTK inhibition or chemo-immunotherapy.

Are there any next steps to answer some of these questions that you have about this analysis?

Some of the next steps would be to attempt to identify some of the risk factors and features of the patients that do relapse early in order to potentially inform clinical practice. Unfortunately, with the granularity of the CIBMTR database, we were able to capture some of the common risk features that we look to in patients with mantle cell lymphoma, such as stage and things like performance status, but we weren't able to glean through the database things like the impact of the KI67 index, the Mantle Cell Lymphoma International Prognostic Index score, TP53 aberrations and other things like that. I think being able to look deeper into those data points would allow us to have a better understanding of which patients are the ones that relapse early and which ones may potentially benefit from consideration of novel therapeutic approaches, if they have early relapse. Hopefully with updates in the CIBMTR, we should have a better granularity in who those patients are.

What are your recommendations for clinical trials going forward with this population?

In our analysis, patients that relapse early had poor overall survival. Essentially, we need to do a better job at employing novel therapeutic approaches in that population of patients. One of the more recently approved therapies or class of drugs in mantle cell lymphoma would be chimeric antigen receptor T-cell therapy, but there are also clinical trials using new novel agents, which would maybe well suited for this space. There's currently new, non-covalently bonding BTK inhibitors in clinical trials, which have shown promise in mantle cell lymphoma, along with other drugs such as antibody-drug conjugates targeting ROR1, which is commonly expressed on mantle cell lymphoma cells as well.