Peter Riedell, MD, Assistant Professor of Medicine, University of Chicago Medicine, discusses the impact of time to relapse on overall survival (OS) over time in patients with mantel cell lymphoma (MCL) following frontline high-dose therapy and autologous hematopoietic cell transplantation (autoHCT), the data of which were presented at the virtual 2021 American Society of Clinical Oncology (ASCO) Annual Meeting.

Transcript

Hi. My name is Peter Riedell. I'm an Assistant Professor at the University of Chicago Medicine.

Our study involved a specific subtype of B-cell non-Hodgkin's lymphoma known as mantle cell lymphoma. This is an uncommon subtype of lymphoma. For those patients that are typically young and fit, the standard treatment approach would involve rituximab- and cytarabine-containing induction therapy, followed by a consolidative autologous stem cell transplant.

Based on data from international clinical trials, that's emerged as a common and effective treatment paradigm in young and fit patients. Despite this aggressive treatment approach, in general, mantle cell lymphoma is considered an incurable disease, though outcomes can certainly be varied.

Previous studies have explored the impact of early disease progression on overall survival in other subtypes of non-Hodgkin's lymphoma, such as follicular lymphoma and DLBCL, although in mantle cell lymphoma, the clinical significance of the timing of relapse following auto transplant and its impact on overall survival is not really well-defined. That's what we aim to tackle in our analysis.

In our study, we were able to utilize the Center for International Bone Marrow Transplant Registry database in order to evaluate the effect of post-auto stem cell transplant time to relapse on overall survival over time in approximately 460 patients who underwent an autologous stem cell transplant within 12 months of being diagnosed with mantle cell lymphoma.

Within our study, we incorporated a dynamic landmark analysis, which was performed at 6-month intervals, spanning 5 years following auto transplant in order to evaluate the impact of time to relapse on overall survival while at the same time adjusting for significant patient and disease-related variables.

Through our analysis, on multivariate analysis, we were able to ascertain some findings, including the impact of relapse on overall survival was greatest in patients relapsing early after their autologous stem cell transplant. The hazard ratio was particularly highest in those patients relapsing by the 6-month, 12-month, and 18-month landmark time points.

Additionally, we used the Cox model with maximum likelihood method limiting to relapsing patients which in that model, it suggested that relapse by 18 months was really the optimum cutoff point to define those patients more in the early relapse category versus late relapse category and to discriminate their different survival outcomes.

Also, using the dynamic landmark model, we were able to demonstrate that adjusted overall survival at 5 years following each landmark time point improved with time for both relapsing and non-relapsing patients.

One of the limitations, I would say, of the current data set is the fact that we weren't able to glean some of the now known risk factors in mantle cell lymphoma. Things like the Ki-67 proliferative index, the mantle cell lymphoma international prognostic index, or MIPI score, was unfortunately not available. We weren't also able to glean things like TP53 aberrations in this data set.

Unfortunately, those are currently factors that we do use to predict prognosis or attempt to in patients with this disease. Those data points weren't available in our analysis. They are available, though, in upcoming CIBMTR data forms.

The hope is that we might be able to repeat this analysis in the future and get a comparison of how things may play out with those known risk factors included. These data points that we do not have as part of the data set but are clinically meaningful are going to be very helpful for us to better understand who these patients are that actually relapse early.

We know that early relapse is essentially associated with worse overall survival, but it would be ideal if we were able to, on the front end, discern which patients are destined to relapse early. Potentially, we could alter their therapeutic strategy from the beginning in order to potentially have better long-term outcomes.

The findings from our study would demonstrate that early relapse, which we defined as less than 18 months following auto transplant, defines this high-risk group with inferior post-relapse overall survival.

Additionally, it does show that patients that relapsed after the 18-month landmark time point experienced a median post-relapse overall survival that was generally favorable, ranging between 44 and 67 months.

Based on the poor overall survival in those patients relapsing early, we would argue that they should be considered for clinical trials or novel therapeutic approaches, including chimeric antigen receptor T-cell therapy at the time of relapse.

This research certainly is important and informative for the field. This research helps to confirm that the time to relapse in mantle cell lymphoma is a dynamic marker, which does extend our ability to provide accurate risk assessment to our patients and to better define optimal management strategies in this disease.