Prognostic Indicators for Mantle Cell Lymphoma

Transcript: Ian Flinn, MD: Bijal, let’s walk through some of these prognostic indices. We talked about some of the individual components, such as p53 and Ki-67, but the MIPI [mantle cell lymphoma international prognostic index] is sometimes used. Do you use that on a regular basis in the treatment of your patients? Do you do it only in clinical trials? How is it used day to day?

Bijal Shah, MD: It’s not very helpful day to day. I do think that for the very high-risk patient, you generally know that before you calculate a MIPI, if you’ve seen a 70-year-old patient with a white blood cell count of 200,000 and massive adenopathy. It’s not a big stretch to say, “This person is going to be high risk.” I think one thing that’s nice is that the MIPI-C—the third revision of the MIPI—builds in the Ki-67 to try and help us better stratify treatment outcomes. I’m hopeful that there will be a biologic MIPI, something perhaps akin to the FLIPI[AC1] [follicular lymphoma international prognostic index], that will help us to better tailor outcomes. It’s a prognostic index, meaning it doesn’t tell us anything about how to treat. It doesn’t tell us that we can really meaningfully reshape their prognosis based on what we’re seeing from MIPI, and I think that’s the hardest part about using this particular algorithm.

I do find PET [positron emission tomography] helpful. I do think that when I see very high avidity on a PET scan, that’s usually a sign to me that there are some things that I should be worried about.

Ian Flinn, MD: High being how high?

Bijal Shah, MD: I worry when it’s over 6. That, for me, is telling me there’s something unusual. Certainly, I’ve seen cases of mantle cell lymphoma where we can have a heterogeneous disease in the same patient, and I’m sure you guys have seen the same, where you have 1 area that’s low avidity and 1 area that’s very bright. If you biopsy a low avidity area, you may find more classical mantle cell lymphoma, followed by a biopsy of the higher avidity site that shows a more aggressive variance. That’s something I find very peculiar, that you can have such a different disease, even within the same patient.

Ian Flinn, MD: It’s almost like the CLL [chronic lymphocytic leukemia] Richter’s transformation type of an analogy, biopsying areas of high avidity. That’s interesting. I haven’t done that, but you bring up an important point that I probably should be [applying] in the future.

Bijal Shah, MD: We’re trying to use it now to guide what we biopsy. We had a couple of experiences like that. As Tycel said, if it’s someone I want to treat or someone I think is going to need treatment, then I really want to make sure I have that PET to help me figure out who I need to send to my surgeons, because I still like to do excisional biopsies for all the reasons that you pointed out earlier.

Ian Flinn, MD: Yes, because you can convince them to go back in. Javier, that was a nice discussion about different prognostic factors and different subgroups, but when you get down to it, how does that change how we manage things? I think we all have a notion that it should be changing how we do things, but does it?

Javier Munoz, MD, MS, FACP: Excellent point. Mantle cell lymphoma is a heterogeneous disease that has a homogenous poor outcome. It’s a disease that does not have a standard of care. You ask different oncologists their preferences for first-line therapy, and you may get different answers. I need to mention that there’s a subset of patients in which you could potentially get away with observation. Memorial Sloan Kettering Cancer Center showed in some data that patients with mantle cell lymphoma who are asymptomatic with low Ki-67 could potentially be monitored without therapy.

Some of these patients could go for more than a year without requiring therapy. Their outcomes were not compromised. I think that is a good starting point for the discussion. Subsequently, in the patients that do need therapy, whether it is because of organ damage, cytopenias, B-cell symptoms, and so on and so forth, 1 size does not fit all. In the past, we would draw this line in the sand and you would have patients that would be younger and older. The reality is that we are trained not to go by chronologic age. We try to go by biologic age. I definitely factor in all of these variables when it comes to my patients.

The guidelines are going to have multiple options. They go from our R-hyper-CVAD [rituximab and cyclophosphamide, vincristine, doxorubicin, and dexamethasone] to R-CHOP [rituximab and cyclophosphamide, doxorubicin, vincristine, and prednisolone] and R-DHAP [rituximab and dexamethasone, high-dose cytarabine, and cisplatin]. Usually, for the younger, stronger, fit patients, they are going to get consolidation with autologous stem cell transplant, followed by maintenance rituximab. The maintenance rituximab data comes from the New England Journal of Medicine. For the patients that are elderly and frail, usually people are going to choose less aggressive combinations, for example bendamustine and rituximab. Usually, you do not follow that particular platform with the maintenance rituximab, at least from German data.

[AC1]Sounds like they’re saying M-FLIPI, but I can’t find anything online that matches. Could it be modified FLIPI?

Transcript Edited for Clarity