Second-Line Treatment Options in Mantle Cell Lymphoma


Brian Hill, MD, reviews second-line treatment options for patients with relapsed/refractory mantle cell lymphoma.

Brian Hill, MD: We know that mantle cell lymphoma is not curable with traditional treatments. The pattern of remissions followed by relapses, and oftentimes with shortening remissions, is unfortunately still fairly common.

The biggest advance in terms of targeted therapies for the treatment of mantle cell lymphoma, certainly over the past 5 years, has been the application of oral BTK [Bruton tyrosine kinase] inhibitors. There are 3 FDA-approved agents in this space. Ibrutinib was chronologically the first approved, followed by acalabrutinib and recently zanubrutinib.

Unless there’s a strong intolerance or counterindications to BTK inhibitors for mantle cell lymphoma, this represents the best class of agents for treatment of relapsed disease. Typically, the response rates are high. But the median duration of response with most BTK inhibitors is 18 to 24 months, maybe longer if it’s used in early lines of therapy. This is in contrast with clinical to chronic lymphocytic leukemia, in which there are very long, durable remissions with continuous therapy with oral BTK inhibitors. With mantle cell lymphoma, unfortunately there is a steady decline in the ability to control the disease with single-agent BTK inhibitors.

In terms of what the typical outcomes might be for patients with relapsed or refractory mantle cell lymphoma, with BTK inhibitors there are at least 2 years, if not longer, in terms of disease control. Unfortunately, what has been seen over the years is that once BTK inhibitors stop working and patients develop resistance, typically the disease becomes very aggressive, and overall survival is often measured in just a few months.

There are third-line options. There are other FDA-approved medications in this space, including lenalidomide and bortezomib. However, when they’re used in third-line or beyond, treatment outcomes are generally pretty poor.

Transcript edited for clarity.

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


  • 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


  • 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
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