Ezzat Elhassadi, MD, consultant hematologist, Hematology Services, University Hospital Waterford, discusses the subtypes of mantle cell lymphoma (MCL).

MCL is a spectrum of diseases, says Elhassadi. It is important to recognize that some patients with MCL present with indolent disease. The majority of these patients harbor a genetic alteration that sets them apart from more aggressive histologies that require immediate treatment. Patients with indolent disease do not need to be treated at the time of their diagnosis. Within MCL, the blastoid variant behaves differently than the classical one does. Moreover, the subset of patients with a very high Ki-67 behave differently than those with low Ki-67. In a study led by Elhassadi, he and fellow investigators demonstrated that the higher the Mantle Cell Lymphoma International Prognostic Index, the worse the outcome. This means that blastoid subtypes, patients with high Ki-67 and 

 disruption, need to be treated differently, explains Elhassadi.

Additionally, certain patients with classical MCL may be being overtreated. The current intervention is intensive induction therapy, autologous stem cell transplant, and rituximab (Rituxan) maintenance. However, a randomized trial will need to be conducted to prove this.

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Dr. Elhassadi on the Subtypes of MCL

Ezzat Elhassadi, MD, consultant hematologist, Hematology Services, University Hospital Waterford, discusses 

 expression and prognosis in mantle cell lymphoma (MCL).

Part of the 10-year single-center experience of 

 status in MCL was to look at immunohistochemistry (IHC) for 

expression. Notably, there was a 100% correlation between 

 profile expression by immunohistochemistry (IHC) and mutation status, says Elhassadi. Moreover, when Sanger sequencing was used by itself, only 3 mutations could be identified in the overexpressed cohort among 6 patients. When next-generation sequencing (NGS) was employed for the overexpressed group, investigators could identify the subclone as well. However, NGS is not used routinely in practice.

Sanger sequencing was used for all the samples, so the patients who had a low expression by IHC did not have underlying mutations—a finding that correlates with the mutation status. Since these data were reported at the 2019 EHA Congress, Elhassadi and colleagues have introduced 

 IHC screening into routine practice. This patient subset is known to have a very dismal outcome. Both the Nordic MCL-1 and -2 trials have reported a median overall survival of 1.3 years in this patient population, suggesting the insufficiency of standard treatment with intensive chemotherapy, transplant, and rituximab (Rituxan) maintenance.

Ezzat Elhassadi, MD, consultant hematologist, Hematology Services, University Hospital Waterford, discusses p53 expression and prognosis in mantle cell lymphoma (MCL).

Dr. Elhassadi on the Relationship Between p53 Expression and Prognosis in MCL

Ezzat Elhassadi, MD, consultant hematologist, Hematology Services, University Hospital Waterford, discusses a 10-year single-center experience with 

At the 2019, ASCO Annual Meeting, Elhassadi presented the 10-year single-center experience data with 

 status in patients with MCL. Twenty-nine previously treated patients were recruited to the study where investigators collected 32 patient samples. Patients received a variety of combinations. Over the study period, which ranged from 2006 to 2016, 11 deaths were reported. Of the 11 deaths, 6 were non-lymphoma—related and 5 were lymphoma-related as a result of disease progression.

These data fell in line with published literature in the field, says Elhassadi. Further analysis from 

 mutation screening in the lymphoma-related cohort revealed that as many as 80% of patients harbored a 

mutation, which is a known poor prognostic indicator in MCL.

Ezzat Elhassadi, MD, consultant hematologist, Hematology Services, University Hospital Waterford, discusses a 10-year single-center experience with TP53 status in mantle cell lymphoma (MCL).

Dr. Elhassadi on 10-Year Single-Center Experience With TP53 Status in MCL

Ezzat Elhassadi, MD, consultant hematologist, Hematology Services, University Hospital Waterford, discusses the outlook of patients with 

Patients need to have their p53 protein intact in order to benefit from chemoimmunotherapy, the frontline standard in MCL, Elhassadi says. Having a mutation in 

 likely means patients won’t benefit from chemotherapy. Chemotherapy may initially debulk their disease, but patients will quickly relapse. That’s why these patients have a poor survival compared with the majority of patients with MCL.

The selective advantage of resistance clones—hitting the normal hematopoietic cells&mdash;allows expansion of resistance clones, Elhassadi adds. This in part explains why using targeted therapy as a second-line treatment will not work as effectively as in the frontline setting. Since there are data that suggest patients with 

 mutations won’t benefit from single-agent ibrutinib (Imbruvica), these patients likely need a combination approach upfront.

Ezzat Elhassadi, MD, consultant hematologist, Haematology Services, University Hospital Waterford, discusses the outlook of patients with p53-mutated mantle cell lymphoma.

Ezzat Elhassadi, MD

Articles

Dr. Elhassadi on the Subtypes of MCL

Dr. Elhassadi on the Relationship Between p53 Expression and Prognosis in MCL

Dr. Elhassadi on 10-Year Single-Center Experience With TP53 Status in MCL

Dr. Elhassadi Discusses the Outlook of Patients With p53-Mutated MCL