Risk Stratification for Mantle Cell Lymphoma

Brad S. Kahl, MD:There are a couple of ways to try to risk stratify mantle cell lymphoma. There’s something called the MIPI, which is the mantle cell IPI, and that uses 4 clinical factors: age, performance status, white blood cell count, and LDH. Our particular patient is high risk if you calculate his MIPI score. There’s actually an online tool that I would suggest people use if you want to generate a MIPI score. It’s not something that you can do by hand, because it’s a complicated mathematical formula. But if you just plug the numbers into the online formula, it’ll give you the MIPI risk score very easily, and that’s what I did for this patient.

You can also do some biologic risk stratification. The best way to do that is to try to get an estimate of the proliferation. So, you can do a Ki67 stain. And we were not provided the Ki67 stain in this particular case. In mantle cell lymphoma, anything over 30% is considered highly proliferative. Anything below 10% is low proliferation. Between 10% and 30% is intermediate proliferation. So, we don’t know that in this case, but those would be the 2 most common ways to risk stratify in mantle cell lymphoma.

Our patient will be high risk by the MIPI score. We don’t know the Ki67 to give him a biologic risk stratification. I would say risk stratification is moderately important. Certainly, if people have high risk disease, their prognosis is not as good as patients who have low risk disease. But it turns out that one of the most important factors for determining risk is age. Many older patients turn out to be high risk, and many younger patients turn out to be low risk. So, what do you do with that?

For many older patients who are high risk, intensifying their therapy is not always a good option because they’re older, they’re more frail, and they can’t take more intensive treatments. I think risk stratification is very helpful for trying to analyze data from single arm studies. It helps you get a sense of the patient population. And the other place that I like to apply risk stratification is when I have patients who are really borderline—someone between the ages of 60 and 65—and I’m trying to decide if I’m going to pursue an intensive treatment strategy or a non-intensive treatment strategy. A lot of times, I’ll use risk stratification to help me decide. If I have a patient in that age group and they have a high risk, I’ll go with more intensive therapy. And if they’re at low risk, I might go with less intensive therapy for their treatment strategy.

For our patient, the one we have here at age 72, I don’t think an intensive treatment strategy is, frankly, appropriate for him. When I look at that data, the outcomes for intensive strategies in older patients do not look that much better than nonintensive treatment strategies, and I don’t think it justifies all the toxicity that intensive treatment strategies bring into play. So, in this case, the risk stratification is not going to change my management decision.

Transcript edited for clarity.

April 2016

• A 72-year-old male presents to his physician complaining of night sweats, intermittent fever (101°-102°) and fatigue lasting 2 months
• PMH: remarkable for hypertension; controlled on a beta-blocker and diuretic
• Physical exam:
  • Right supraclavicular lymph node, markedly enlarged
  • Spleen, palpable
• Laboratory findings:
  • Leukocytes, 6.73 X 10⁹/L
  • LDH, 420 U/L
• Excisional biopsy of the right supraclavicular node:
  • Immunophenotyping: IgD+, CD5+, CD10+, CD19+, CD20+, CD22+, CD23-, cyclin D1+
  • Cytogenetics: t(11;14)(q13;q32)
  • Bone marrow biopsy confirmed the presence of cyclin D1+ lymphoid cells
• PET-CT: diffuse¹⁸F-FDG uptake in lymph nodes and spleen; the largest involved nodes are the right supraclavicular (4.2 cm), right mesenteric (3.8 cm), and splenic hilar (5.7 cm) nodes
• Diagnosis: Mantle-cell lymphoma, Ann Arbor stage IV
• The patient was started on therapy with bendamustine + rituximab

November 2016

• PET/CT findings at 3 months and 6 months showed a partial response to upfront chemoimmunotherapy
• The patient continues to report symptoms of fatigue
• He was started on therapy with ibrutinib