Dr Elhassadi Highlights the Impact of a p53 Alteration in Patients With MCL

Ezzat Elhassadi, MD, Consultant Hematologist, University Hospital, Waterford, Ireland, discusses the impact of a p53 alteration in patients with mantle cell lymphoma (MCL); these data were presented at the EHA2021 Virtual Congress.

Transcript

Hi. My name is Dr. Elhassadi. I'm a Consultant Hematologist at University Hospital, Waterford, in Ireland. I'm Associate Professor with the Royal College of Surgeons Medical School.

P53 alteration is an important gene in tumor pathogenesis and alteration of this gene resulted in resistance to the standard chemotherapy we use for different lymphomas. This has been approved in CLL, chronic lymphocytic leukemia, to help us to decide what therapeutic decision so a patient with p53 alteration should not be treated with chemotherapy and treated by novel agents.

On that basis, I thought this applicable for MCL. For that reason, we looked at our cohort patients, evaluating the impact of a p53 alteration in MCL.

It's a retrospective study, collecting patient samples and clinical data from 2006 to 2020. Over the study period, beside patient demographics, we reviewed the patient biopsies with MCL. We looked at p53 suppression by immunohistochemistry. In a subset of patients, we did Sanger Sequencing. In a few patients, we did Next Generation Sequencing (NGS) to correlate the p53 immunohistochemistry suppression with the mutational status.

Also, we reviewed our cohort patient survival data in terms of progression-free survival (PFS) and overall survival (OS). In terms of finding in 29 patients with 33 samples, we confirmed 100 percent concordance between p53 suppression by immunohistochemistry with the mutational status, using either Sanger Sequencing or using NGS.

Also, we confirmed the dismal outcome of MCL patient (with a) p53 alteration when they were treated with chemoimmunotherapy. The most interesting part of this project, we have noticed a subclone with p53 alteration wasn't picked up by Sanger Sequencing, but when we did NGS, we could pick up a subclone with high sensitivity assay with NGS.

The same has been done previously. In CLL we confirmed that the NGS could pick up subclone, cannot be picked by Sanger Sequencing in MCL.

Now there is a very solid data to confirm that MCL with p53 alteration, they have a very dismal outcome. There are a few trials running at the moment to see if using chemo-free approach with novel agents independent on p53 mechanism to be considered in this very high-risk group of MCL.

In our routine practice, we incorporated p53 immunohistochemistry screening in all our Mantle Cell. At this stage, it has prognostic implications, but it's not used to decide what treatment to consider up front. I'm hoping with the maturing of different trial would justify using novel agents in this very high group.

In our practice, yes, we do it but no, it hasn't changed how we treat those patients. But we do it for every patient, any new patient with MCL. 

Now, we move to a different stage where we submitted our abstract for the work we have done as a multi-center project. Hopefully, it will be accepted for ASH.

We managed to enroll 101 patients with MCL. We extended our immunohistochemistry screening for p53 and the mutation for all the samples we have. We included relapsed disease samples. In total, in the project we submitted to ASH this year, we have 124 biopsy samples where we managed to do p53 screening by immunohistochemistry and Sanger Sequencing.

It's maturing, evolving evidence that using novel agents in this high-risk group will be beneficial for patients. Even novel agent combinations will be the right approach for this high-risk group. In younger patients, I think up front or very early in relapsed disease, donor allergenic bone marrow transplants should be considered for those patients.

Now, there is emerging data on CART-T cell therapy in this disease. Hopefully, when the data matures enough, seeing this approach in very early disease course for this high-risk group, certainly, it will change the dismal outcome of this high-risk disease.