Mantle cell lymphoma medical therapy

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ali Akram, M.B.B.S.[2]

The mainstay of treatment for mantle cell lymphoma is chemotherapy. However, immunotherapy, radioimmunotherapy, targeted therapy using newer biologic agents and stem cell transplantation are also used along with chemotherapy to treat the disease. Mantle cell lymphoma shows a heterogeneous clinical behavior, with some patients having indolent disease whereas a vast majority show aggressive presentation. Most of the patients eventually relapse and have disease progression after treatment. Hence, mantle cell lymphoma is still considered an incurable disease and there is no consensus among oncologists about its optimal treatment. It is therefore recommended that mantle cell lymphoma patients are seen by physicians having extensive experience in dealing with mantle cell lymphoma and they are also encouraged to participate in clinical trials to get the latest treatments.

Mantle cell lymphoma shows a heterogeneous clinical behavior, with some patients having indolent disease whereas a vast majority show aggressive presentation. Most of the patients eventually relapse and have disease progression after treatment. Hence, mantle cell lymphoma is still considered an incurable disease and there is no consensus among oncologists about its optimal treatment. It is therefore recommended that mantle cell lymphoma patients are seen by physicians having extensive experience in dealing with mantle cell lymphoma and they are also encouraged to participate in clinical trials to get the latest treatments.

• Different types of treatment currently being used to treat mantle cell lymphoma are as follows:
  • Chemotherapy
  • Immunotherapy
  • Radioimmunotherapy
  • Targeted therapy using newer biologic agents
  • Stem cell transplantation

• Radiotherapy alone or combination chemoimmunotherapy with or without radiotherapy is recommended.^[1]
• For patients with complete response(CR), clinical follow up is conducted every 3-6 months for 5 years, and then on a yearly basis.
• For patients treated with radiotherapy alone initially, disease progression and relapses after a CR or partial response(PR) is treated with first-line induction therapy (recommended for stage II bulky and stage II-IV disease)
• For patients treated with chemoimmunotherapy with or without radiotherapy, disease progression and relapses after a CR or PR is treated with second-line therapy regimens (recommended for stage II bulky and stage II-IV disease)

• Aggressive therapy:^[2]
  • Hyper-CVAD (cyclophosphamide, vincristine, doxorubicin (also known by its trade name, Adriamycin), and dexamethasone) + rituximab
  • Dose-intensified CHOP (cyclophosphamide, hydroxydaunorubicin, oncovin (vincristine) and prednisone) alternating with rituximab + high-dose cytarabine (NORDIC regimen)
  • Rituximab and methotrexate with augmented CHOP
  • Sequential R-CHOP and R-ICE (Ifosfamide, carboplatin, etoposide)
  • Alternating R-CHOP and R-DHAP (Dexamethasone, High dose Ara-C Cytarabine, Platinol)
• Less aggressive therapy:
  • Bendamustine + rituximab
  • Bortezomib, rituximab, cyclophosphamide, doxorubicin, and prednisone (VR-CAP)
  • Cladribine + rituximab
  • CHOP + rituximab (R-CHOP)
  • Modified Hyper-CVAD with rituximab maintainence in patients older than 65 years.
• For patients with CR to first-line therapies, HDT/ASCR (High dose therapy/Autologous Stem Cell Rescue) or clinical trial participation is recommended. Follow up is conducted every 3-6 months for 5 years, and then on a yearly basis.
• For patients with PR to first-line therapies, second-line therapies may be considered.

• HDT/ASCR is recommended.^[3]
• Patients who are not HDT/ASCR candidates, and are in remission after R-CHOP therapy, may get rituximab maintenance therapy every 8 weeks.

• The following therapies may be used in relapsed/refractory disease:^[4]
  • Bendamustine +/- rituximab
  • Bortezomib +/- rituximab
  • Cladribine +/- rituximab
  • FC (fludarabine, cyclophosphamide) +/- rituximab
  • FCMR (fludarabine, cyclophosphamide, mitoxantrone, rituximab)
  • FMR (fludarabine, mitoxantrone, rituximab)
  • Lenalidomide +/- rituximab
  • PCR (pentostatin, cyclophosphamide, rituximab)
  • PEPC (prednisone, etoposide, procarbazine, cyclophosphamide) +/- rituximab
  • Ibrutinib
• Autologous stem cell transplant and allogeneic stem cell transplant can be used as second-line maintenance therapy for patients in remission with relapsed or refractory disease.