Brukinsa
zanubrutinib
FDA Approved 2019 2nd Line+ NEW
Approved Indications (US/FDA)
Treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy.
Dosing Schedule
160 mg orally twice daily or 320 mg once daily
Cycle Length
Continuous daily dosing
Combination Therapy
Monotherapy (next-generation BTK inhibitor)
Manufacturer
BeiGene
Approval Year
2019
Pivotal Trial
NCT03206970 ↗
Key Publication
Song et al. JCO 2020 ↗
Tecartus
brexucabtagene autoleucel
FDA Approved 2020 2nd Line+ NEW
Approved Indications (US/FDA)
Treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL).
Dosing Schedule
Single IV infusion of CAR T cells (target dose: 2 × 10⁶ CAR-positive viable T cells/kg, max 2 × 10⁸)
Cycle Length
Single infusion (preceded by lymphodepleting chemotherapy)
Combination Therapy
Autologous CD19-directed CAR T-cell therapy
Manufacturer
Kite/Gilead
Approval Year
2020
Pivotal Trial
NCT02601313 ↗
Key Publication
Wang et al. NEJM 2020 ↗
Jaypirca
pirtobrutinib
FDA Approved 2023 3rd Line+ NEW
Approved Indications (US/FDA)
Treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL) after at least two lines of systemic therapy, including a BTK inhibitor.
Dosing Schedule
200 mg orally once daily
Cycle Length
Continuous daily dosing
Combination Therapy
Monotherapy (non-covalent, reversible BTK inhibitor)
Manufacturer
Eli Lilly
Approval Year
2023
Pivotal Trial
NCT03740529 ↗
Key Publication
Mato et al. Lancet 2021 ↗

Overview of Mantle Cell Lymphoma Treatment

Mantle cell lymphoma treatment depends on fitness for intensive therapy. Younger patients typically receive intensive chemoimmunotherapy with autologous stem cell transplant, while older patients receive less intensive rituximab-based regimens. BTK inhibitors (ibrutinib, acalabrutinib, zanubrutinib) are standard for relapsed disease, with pirtobrutinib as a non-covalent option for BTK inhibitor-refractory patients. CAR-T (brexucabtagene autoleucel) offers potential deep responses.

Treatment Sequencing

First-Line (Transplant Eligible)

  • Intensive chemoimmunotherapy + autologous SCT
  • R-DHAP or R-HyperCVAD

First-Line (Transplant Ineligible)

  • BR (bendamustine-rituximab) or VR-CAP
  • Ibrutinib + rituximab (SHINE)

Relapsed/Refractory

  • BTK inhibitors: ibrutinib, acalabrutinib, zanubrutinib
  • Pirtobrutinib (Jaypirca) — post-BTK inhibitor
  • Brexucabtagene autoleucel (Tecartus) — CAR-T

Epidemiology & Impact

Mantle cell lymphoma accounts for 5-7% of NHL with roughly 5,000 new cases annually. It has a 3:1 male predominance and median age of 68. MCL historically combined incurability with aggressiveness, though modern therapy has improved outcomes. A subset (10-15%) has indolent leukemic non-nodal MCL suitable for observation.

Molecular Biology & Biomarkers

MCL is defined by t(11;14) translocation causing cyclin D1 overexpression. Additional mutations in ATM (40-55%), TP53 (20-30%, poor prognosis), and NOTCH1/2 drive pathogenesis. Ki-67 and TP53 status are the strongest prognostic factors. Blastoid and pleomorphic variants are particularly aggressive.

Evolving Treatment Landscape

Younger fit patients receive intensive chemoimmunotherapy with high-dose cytarabine and autologous transplant. Older patients receive bendamustine-rituximab. BTK inhibitors (ibrutinib, acalabrutinib, zanubrutinib) achieve 65-80% responses in relapsed MCL. CAR-T therapy (brexucabtagene autoleucel) achieves over 60% complete responses. Pirtobrutinib provides options after covalent BTK inhibitor failure.

Approved Therapies