73-Year-Old Man With Mantle Cell Lymphoma

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Brian Hill, MD:This is the case of a 73-year-old man with mantle cell lymphoma. He was diagnosed in 2016, and at the time he was treated with a regimen called R-DHAP: rituximab, dexamethasone, cytarabine, and cisplatin. This was followed by autologous stem cell transplant, which would have been appropriate for a generally fit patient in their 60s or 70s.

He achieved a response, perhaps just a partial remission, but then continued maintenance therapy with rituximab every 2 months thereafter. Now he has been shown to be a standard of care. At the time of diagnosis, he had stage IV disease and a MIPI [Mantle Cell Lymphoma International Prognostic Index] score of 6.7, which is high risk. Within a relatively short period of time—3 years later—in late 2019, the patient relapsed. At the time he was started on the oral BTK [Bruton tyrosine kinase] inhibitor ibrutinib. With this therapy, he had stable disease. Now he comes in with about a 2-month history of loss of appetite and worsening fatigue, but he is otherwise generally healthy. He has hyperlipidemia and some standard comorbidities, which is common in this patient group.

On physical exam, he has bilateral, cervical, and supraclavicular lymphadenopathy. His laboratory studies are notable for white blood cell count of 11,000 per mm3 with 3000 neutrophils. Hemoglobin is 9.5 g/dL, and platelet count is 96,000 per mm3. His serum lactate dehydrogenase level was 405 U/L, and a biopsy confirmed progressive mantle cell lymphoma. On the biopsy, a cyclin D1-positive population of small to medium-size lymphocytes that are positive for CD5 and have a translocation of 11;14, consistent with recurrent or progressive mantle cell.

On staging scans, a CT scan shows widespread lymphadenopathy, including the supraclavicular stations as well as AML [acute myeloid leukemia] regions. This is confirmed on PET scans, those nodes are noted to be FTT [failure to thrive] avid, as one would expect. The performance status of this patient is good. Other than just a little fatigue, he had an ECOG performance status of 0. At this point, he was treated with lymphodepletion with fludarabine and cyclophosphamide followed by CAR [chimeric antigen receptor] T-cell therapy.

What is known about mantle cell lymphoma is that it’s generally an aggressive disease with a bit of a range of prognoses, depending on the Mantle Cell [Lymphoma] International Prognostic Index, which considers a number of clinical factors, including the age and stage of the patient, but also is calculated based on the extent of proliferation index of the biopsy as measured by Ki-67.

This patient had a high-risk MIPI score, but even patients with lower- or intermediate-risk MIPI scores are generally treated with intensive chemotherapy regimens and autologous stem cell transplant if they’re eligible for it.

It does not come as a surprise that the patient had only a few years of remission with the treatment he had, but patients who have earlier relapse tend to have poor outcomes in general with mantle cell.

Transcript edited for clarity.

Case: A 73-Year-Old Male With Mantle Cell Lymphoma

History

• A 73-year-old man was diagnosed with mantle cell lymphoma in 2016
• He was treated with rituximab, dexamethasone, cytarabine + carboplatin followed by autologous stem cell transplant; achieved PR; continued rituximab maintenance therapy
• Ann Arbor stage IV; MIPI score 6.7, high risk
• Late 2019 he experienced clinical relapse and was started on ibrutinib; achieved SD
   

Currently

• He complains of a 2-month history of loss of appetite and fatigue
• PMH: hyperlipidemia, medically well-controlled
• PE: bilateral clavicular and cervical lymphadenopathy; otherwise unremarkable
• Labs: WBC 11 X 109/L, hemoglobin 9.5 gm/dL, plt 96,000/u, LDH 405 U/I, ANC 3200/mm3
• Lymph node biopsy: IHC; cyclin D1+, CD5 +, CD10+, CD20+, FISH: t (11;14)
• C/A/P CT scan: widespread lymphadenopathy including bilateral clavicular (2.4 cm, 1.5 cm), and inguinal region (4.6 cm)
• PET/CT shows diffuse uptake of 18F-FDG in the clavicular, axillary and inguinal lymph nodes
• Beta-2-microglobulin 4.1 µg/L
• ECOG PS 0
• Treatment was started with fludarabine + cyclophosphamide, followed by a single infusion of CAR T-cell therapy