Investigational Therapy in Mantle Cell Lymphoma: KTE-X19 CAR T-Cell Therapy - Episode 1

Risk Stratification of Mantle Cell Lymphoma

Michael Wang, MD: Risk stratification, in my opinion, is 1 of the most critical things in the art of treating a patient with a lymphoma. In my opinion, everybody is different. Everybody’s tumor is different. In some cases, in almost all cases, each patient’s tumor, in each part of the body of that patient, is also different. So risk stratification lies in the heart of the therapy.

When we do clinical trials, we usually use 1 or 2 therapies to treat many patients. Patients are all labeled with the same diagnosis—let’s say mantle cell lymphoma—but the disease is different in each patient and among all patients. Therefore, when we treat all these different patients with 1 or 2 therapies, outcomes vary. Some patients with low-risk factors get overtreated. Some patients with high-risk factors get undertreated. Usually, those in the middle get the right therapy. But every cohort—low risk, moderate risk, high risk—could be further risk stratified. So risk stratification is 1 of the most important things used to treat mantle cell lymphoma in daily practice. That is my opinion.

For mantle cell lymphoma, high-risk features include a TP53 mutation and a high MKI67 percentage of over 30%. People with over 50% have an even worse prognosis, and we also have patients who have complex karyotype. This means they have chromosomal abnormalities excluding the 11;14 translocation. There are 3 or more chromosomal abnormalities we call the complex karyotype.

Also, in mantle cell lymphoma morphology, a blastoid or pleomorphic variant puts a person as higher risk. In summary, TP53, MKI67, pleomorphic or blastoid karyotype, or complex karyotype are all high-risk features.

This is only the beginning of what I’m describing. Actually, how to risk stratify is even more complicated. There’s the MIPI [Mantle Cell Lymphoma International Prognostic Index] score. There are additional chain mutations. There is bulky tumor load. There’s also relapse within 24 months. Those are all data-driven risk factors. That’s why it’s very complicated to treat a mantle cell lymphoma patient.

A patient who has had 3 prior therapies has automatically transformed into a very complex high-risk mantle cell lymphoma patient. Those people who were treated with 3 prior therapies, including a BTK [Bruton tyrosine kinase] inhibitor, have only about 6 to 10 months’ delay. The risk stratification is complicated, but their high-risk factors continue to grow with more genetic testing and more data from trials and daily practice.

The MIPI score considers a patient’s age, performance status, LDH [lactate dehydrogenase], and WBC [white blood cell] count. MIPI is a very important prognostic factor. One of the main reasons why MIPI is so reliable is because it considers age and performance status in addition to other laboratory parameters.

In Sweden it was published that age and performance status affected overall survival. MIPI is very important, especially when the patient is newly diagnosed. When MIPI is combined with the Ki-67, that’s even more reliable. It’s able to categorize the survival of the mantle cell lymphoma patient very nicely.

However, most of the time clinicians don’t calculate the MIPI score. If you treat mantle cell lymphoma, you already automatically and intuitively categorize the patient based on different risk factors. When you calculate them in a MIPI score—your clinical mutations are consistent with the MIPI. I think MIPI is very useful. Especially as we publish papers and data, MIPI is very important to see, to gauge whether a patient is actually part of a low-risk population, a moderate-risk population, or a high-risk population. In my opinion, MIPI is very useful.

Transcript edited for clarity.