Dr Moustafa on Standard Treatment Approaches in MCL

Muhamad Alhaj Moustafa, MD, MS, hematologist, medical oncologist, Departments of Hematology and Oncology (Medical), Mayo Clinic, discusses standard treatments for transplant-eligible and transplant-ineligible patients with mantle cell lymphoma (MCL).

The standard first-line treatment approach for transplant-eligible patients with MCL typically consists of a chemoimmunotherapy combination, such as rituximab (Rituxan) plus chemotherapy, Moustafa says. Other potential treatment regimens for patients in this population include bendamustine-rituximab and hyperfractionated cyclophosphamide, vincristine, doxorubicin hydrochloride, and dexamethasone (hyper-CVAD), Moustafa notes. If these patients achieve a complete response (CR) with initial induction therapy, they will often receive subsequent autologous stem cell transplant (ASCT), Moustafa explains. Patients who continue to experience CR with ASCT will then receive maintenance therapy with rituximab for approximately 3 years, according to Moustafa.

Conversely, transplant-ineligible patients with MCL typically receive chemoimmunotherapy, which may be followed by maintenance rituximab, Moustafa emphasizes. Transplant-ineligible patients who cannot tolerate chemoimmunotherapy, including elderly patients or those with comorbidities, may benefit from off-label treatment with BTK inhibitors, Moustafa concludes. 

The current arsenal of FDA-approved BTK inhibitors for patients with pretreated MCL includes acalabrutinib (Calquence), zanubrutinib (Brukinsa), and pirtobrutinib (Jaypirca). Acalabrutinib received accelerated approval in 2017 and Zanubrutinib was granted accelerated approval in 2019. Both approvals were for the treatment of adult patients with MCL who have received at least 1 prior therapy.

Acalabrutinib and zanubrutinib are covalent BTK inhibitors. Ibrutinib (Imbruvica), another covalent BTK inhibitor, was granted accelerated approval in 2013 for patients with MCL who had received at least 1 prior therapy. However, in 2023, this indication was voluntarily withdrawn by AbbVie. 

The first noncovalent BTK inhibitor to gain approval for adult patients with previously treated MCL was pirtobrutinib, which received accelerated approval in 2023 for the treatment of adult patients with disease that is relapsed/refractory to at least 2 lines of systemic therapy, including a prior BTK inhibitor.