Carlo Visco, MD, Associate Professor, Department of Medicine, Section of Hematology, University of Verona, Italy, discusses rituximab, bendamustine, and cytarabine followed by venetoclax for high-risk elderly patients with mantle cell lymphoma (MCL). These data were presented at the 2021 American Society of Hematology (ASH) Annual Meeting.

Transcript

Hi, everybody. My name is Carlo Visco. I'm a professor of hematology at the University of Verona in Department of Medicine, which is located in the Northeast of Italy.

This research on V-RBAC comes from far away, actually, from our previous studies, which has been conducted by the Fondazione Italiana Linfomi, the FIL, was called R-BAC500 that was presented at this conference a couple of years ago.

After conducting that study, we observed that patients with some characteristics that we call high-risk features didn't do that well with R-BAC. This prompted us to develop this newer study, which is called the V-RBAC, which added a molecule called the anti-BCL-2 molecule venetoclax to the R-BAC regimen in selecting the patients since the beginning and divided them between low-risk and high-risk patients.

The study included patients that were not candidates to autologous transplant frontline, which means that these patients with MCL were elderly patients more than 65 years old or even younger if they were not candidate to transplant. The trial did not encompass patients with indolent forms of MCL.

Basically a patient was stratified prospectively after studying via diagnosis into a centralized fashion by means of a Ki67 or the kinetics of the tumor, 53 mutations or deletions or the presence of a morphologic blastoid variant, which means that the patient that with at least 1 of these risk factors were considered as high-risk patients.

These patients were treated differently from low-risk patients, from those with the standard risk factors. The standard risk factors population was treated with 6 cycles of R-BAC, which is the standard at least in Italy, while the high-risk population was treated with R-BAC with a short course of R-BAC, I would say, followed by consolidation with venetoclax 800 mg and then maintenance up to 2 years with venetoclax 400 mg per day.

The study was meant to enroll 52 patients according to our high-risk definition. Indeed, we enrolled the number of patients. These were part of a total of 140 overall prospectively enrolled elderly patient with MCL.

Overall, we found that approximately 40 percent of patients presenting with MCL, and the elderly population have high-risk features. This needs to be considered in future trials. When designing future trials, since the identification of these patients, early diagnosis is going to be useful for differentiating treatment of these patients.

As you all know, clinical behavior of this bunch of patients with a standard immunochemotherapy is not satisfactory, irrespective of the chemotherapy of the immunotherapy you give. There's an urgent need for taking molecules and newer molecules upfront to this high-risk population.

Our clinical findings will help, at least, in this phase, clinicians in stratifying patients upfront, which is very important at least together with a good pathological diagnosis with MCL.

Our findings, I think we'll need to be now validated with our follow-up. At the present, we don't have any clue on the response and the clinical behavior of this patient divided accordingly will update our results in future meetings because we are very keen to see whether the addition of venetoclax has at least a little bit improved to the expected outcome of this high-risk patients.

We really look forward to our progression-free survival and overall survival results and stratified according to the risk factors we have identified. This is the first prospective trial, at least to my knowledge ever, that a stratified patient biologically have diagnosis and differentiated treatment, depending on the risk.

At least initially I have performed stratification based on 1, 2, or 3 hits, depending on the risk factors the patients had. With this research after looking at the data, the patient can be differentiated into 3 main categories, depending on the presence of 53 aberrations alone, without any high-kinetic factor, without blastoid variants.

Then there's another bunch of patients that have more factors together, so meaning that 53 aberrations together with the kinetic or blastoid. There's also as more bunch of patients that have the wild-type 53 but have high-kinetic factor.

I will be very interested in see how these three groups behave in the next future. I will look forward to be an update for the scientific community how it represents in the end.