A Case of Mantle Cell Lymphoma: Initial Impressions

Michael L. Wang, MD:This is a 55-year-old gentleman, a man in the most productive time of his life to our society, who has no significant past medical history but started complaining of symptoms such as weight loss and neck swelling. And so, he was diagnosed with mantle cell lymphoma. His lymphoma, I think, is high-risk, because he has a 9-cm mass in his abdomen. Cyclin D1 was positive. Cyclin D1 is pathognomonic for the diagnosis of mantle cell lymphoma. You have to have either translocation 11;14 or cyclin D1 in order for you to diagnose mantle cell lymphoma. The patient has both. He has translocation 11;14, and he also had cyclin D1 positivity. Very, very importantly, he is CD20-positive. As we all know, CD20 is one of the most important immune markers for our therapy with rituximab. So, CD20 in this case is also described to be positive. Those are all very consistent with a mantle cell lymphoma diagnosis.

After the diagnosis, the patient was staged, and because there no bone marrow involved, he was diagnosed with stage 3, which I agree with. This patient, in my opinion, has moderate- to high-risk disease, because his MIPI score is high, over 6, and there’s also a bulky tumor in his abdomen—up to 9 cm. So, they’re all bad prognostic features. If this patient is treated with standard therapy, such as hyper-CVAD [cyclophosphamide, vincristine, doxorubicin, and dexamethasone] followed by autologous stem cell transplant—we call this Nordic therapy. Nordic therapy is induction therapy followed by frontline autologous stem cell transplantation. The induction therapy varies according to different versions of Nordic therapy and according to interpretation by other colleagues in America. Some people use DHAP [dexamethasone, high-dose cytarabine, and cisplatin], some people use bendamustine/rituximab, and a lot of people use hyper-CVAD followed by stem cell transplant. So, although the induction therapies vary, the universal use is stem cell transplantation.

This patient was treated according to the standard of care. Of course, referring to standard of care, there’s no such a thing as standard of care in mantle zone lymphoma, because it’s such a rare disease. Phase III clinical trials are almost never done—they are coming, by the way, but so far in history they were never performed. Some people use Nordic therapy. A lot of American colleagues who specialize in mantle cell lymphoma use 6 to 8 cycles of hyper-CVAD without the Nordic autologous stem cell transplantation. Hyper-CVAD is the MD Anderson Cancer Center method of treating mantle cell lymphoma. Hyper-CVAD was developed for mantle cell lymphoma from The University of Texas MD Anderson Cancer Center. So, this patient was treated with the standard of care and achieved a good response.

Transcript edited for clarity.

March 2013

• A 55-year-old male presents to his physician complaining of fatigue, unexplained weight loss, and neck swelling
• PMH: unremarkable
• Physical exam:
  • Bilateral cervical lymphadenopathy
• Laboratory findings:
  • Leukocytes, 9.0 X 10⁹/L
  • Hb, 9.8 g/dL
  • LDH, 520 U/L
  • Beta2-microglobulin; 6.4 mg/L
  • AST, 167 U/L; ALT 202 U/L
• Excisional biopsy of the right cervical node:
  • Immunophenotyping: IgM+, CD5+, CD10-, CD19+, CD20+, CD22+, CD23-, cyclin D1+
  • Cytogenetics: t(11;14)(q13;q32)
• CT imaging of the neck, chest, abdomen, pelvis: marked¹⁸F-FDG uptake and enlargement of bilateral cervical lymph nodes (right, 4.6 cm; left, 3.1 cm) and mesenteric lymph node (9.2 cm)
• Diagnosis: Mantle-cell lymphoma, Ann Arbor stage III
• The patient was started on induction therapy with R-hyper-CVAD and achieved significant reduction in tumor burden
• Consolidation with autologous stem cell transplant resulted in complete remission

March 2017

• The patient reports having symptoms of fatigue and weight loss
• PET/CT shows diffuse uptake of¹⁸F-FDG in the right lung and mediastinal lymph nodes
• The patient was started on therapy with ibrutinib