Mantle Cell Lymphoma: Overview and Standard of Care

Javier Munoz, MD, MS, FACP: Mantle cell lymphoma comprises approximately 7% of adult patients with non-Hodgkin lymphoma in the United States, with an incidence of around 7 cases per million persons per year. Incidence increases with age, and most patients are male Caucasians. Median age at diagnosis is 68 years old. To summarize, the most frequent clinical presentation would be in an older Caucasian man.

The diagnosis is based on pathologic evaluation of tissue, either via a bone marrow biopsy or a lymph node biopsy. An excisional lymph node biopsy is always preferred when it comes to lymphomas, in general.

Mantle cell lymphoma is also associated with a translocation of chromosomes 11 and 14, like in this case, that dysregulates the cyclin D1 gene. Acquisition of additional genetic abnormalities such as translocations involving MYC or TP53 abnormalities can lead to progression, to more aggressive forms of mantle cell lymphoma with blastoid or pleomorphic morphologies.

The National Comprehensive Cancer Network Guidelines, or NCCN Guidelines, divide options into less aggressive and aggressive therapies. The latter option comes with the intention to consolidate with high-dose chemotherapy followed by autologous stem cell transplantation, usually followed by maintenance rituximab. There are many pathways that can get you there, and certainly it’s good to have options. You have hyper–CVAD [cyclophosphamide, vincristine, doxorubicin, dexamethasone]. You also have R-CHOP [rituximab, cyclophosphamide, hydroxydaunorubicin hydrochloride, vincristine, prednisone] alternating with R-DHAP [rituximab, dexamethasone, cytarabine, cisplatin], among other options to put the patient into complete remission for the first time. That is usually when we provide the autologous stem cell transplantation maneuver.

The maintenance rituximab data after autologous stem cell transplant come from a publication in the New England Journal of Medicine in 2017. The publication showed a progression-free survival at 4 years of 79% in the rituximab group, vs 61% in the other group. Furthermore, rituximab maintenance provided a statistically significant overall survival advantage and should be considered as standard of care after autologous stem cell transplant.

How do you get to autologous stem cell transplant? The answer is through these aggressive options mentioned in the NCCN Guidelines, which include the hyper-CVAD [cyclophosphamide, vincristine, doxorubicin, dexamethasone] or R-CHOP [rituximab, cyclophosphamide, hydroxydaunorubicin hydrochloride, vincristine, prednisone] alternating with R-DHAP [rituximab, dexamethasone, cytarabine, cisplatin] and the Nordic regimen [rituximab, cyclophosphamide, hydroxydaunorubicin hydrochloride, vincristine, prednisone]. The disclaimer is that this is a rare disease, hence there is no consensus when it comes to frontline therapy, and guidance may be based on personal or institutional preferences. Needless to say, we always encourage participation in clinical trials, and there are indeed attractive options in the frontline setting as well.

Transcript edited for clarity.

Case: A 66-Year-Old Woman With Mantle Cell Lymphoma

History

• A 66-year-old woman diagnosed with mantle cell lymphoma in 2017
• She was treated with rituximab, dexamethasone, cytarabine + carboplatin followed by autologous stem cell rescue; achieved PR;
  • Continued on rituximab maintenance therapy
• In 2019 she experienced clinical relapse and was started on acalabrutinib; achieved SD
   

Currently

• She complains of a 3-month history of intermittent fatigue, nausea and dyspnea on exertion
• PMH: DM, medically controlled
• PE: bilateral submandibular lymphadenopathy; otherwise unremarkable
• Labs: WBC 12 X 109/L, hemoglobin 9.8 gm/dL, plt 90,000/u, LDH 410 U/I, ANC 3100/mm3
• Lymph node biopsy: IHC; cyclin D1+, CD10+, CD20+, CD43+; FISH: t (11;14)
• C/A/P CT scan: widespread lymphadenopathy including bilateral submandibular (2.9 cm, 3.4 cm), 2 left-sided axillary lymph nodes (3.7 cm, 4.1 cm), and lumbar region (5.1 cm)
• PET/CT shows diffuse uptake of 18F-FDG in the submandibular, axillary and lumbar lymph nodes
• Beta-2-microglobulin 4.2 µg/L
• Ann Arbor stage IV; MIPI score 6.6, high risk; ECOG PS 0
• Treatment was started with fludarabine + cyclophosphamide, followed by a single infusion of CAR transduced autologous T cell