Mantle cell lymphoma medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Medical Therapy

There are no proven standards of treatment for MCL, and not even consensus among specialists on how to treat it optimally. Many regimens are available and often get good response rates, but patients almost always get disease progression after chemotherapy. Each relapse is typically more difficult to treat, and relapse is generally faster. Fortunately, regimens are available that will treat relapse, and new approaches are under test. Because of the aforementioned factors, many MCL patients enroll in clinical trials to get the latest treatments.

There are four classes of treatments currently in general use: chemotherapy, immune based therapy, radioimmunotherapy and new biologic agents. The phases of treatment are generally: frontline, following diagnosis, consolidation, after frontline response (to prolong remissions), and relapse. Relapse is usually experienced multiple times.

Chemotherapy

Chemotherapy is widely used as frontline treatment, and often is not repeated in relapse due to side effects. Alternate chemotherapy is sometimes used at first relapse. For frontline treatment, CHOP with rituximab (Rituxan, Mabthera) is the most common chemotherapy, and often given as outpatient by IV. A stronger chemotherapy with greater side effects (mostly hematologic) is HyperCVAD, often given as in-patient, with rituximab and generally to fitter patients (some of which are over 65). HyperCVAD is becoming popular and showing promising results, especially with rituximab. It can be used on some elderly (over 65) patients, but seems only beneficial when the baseline Beta-2-MG blood test was normal. It is showing better complete remissions (CR) and progression free survival (PFS) than CHOP regimens. Another chemotherapy class is fludarabine monotherapy, sometimes combined with cyclophosphamide and mitoxatrone, usually with rituximab. Cladribine and clofarabine are two other drugs being investigated in MCL. Cytotoxic chemotherapies, including bendamustin, are being studied alone and with similar combinations. A relatively new regimen that uses old drugs is PEP-C, which includes relatively small, daily doses ofprednisone, etoposide, procarbazine, and cyclophosphamide, taken orally, has proven effective for relapsed patients[2].

Another approach involves using very high doses of chemotherapy, sometimes combined with total body irradiation (TBI), in an attempt to destroy all evidence of the disease. The downside to this is the destruction of the patients' entire immune system as well, requiring rescue by transplantation of a new immune system, using either ones' own previously treated and stored stem cells (an autologous stem cell transplant), or those from a matched donor (an allogeneic stem cell transplant).

Immunotherapy

Immune-based therapy is dominated now by the oft used and effective rituximab monoclonal antibody, sold under the trade name Rituxan (or as Mabthera in Europe and Australia). Some say it is a landmark medicine. It can have good activity against MCL alone but especially in combination with chemotherapies to prolong response duration. Rituximab essentially tags the cancer cells for destruction by the body. There are newer variations on monoclonal antibodies combined with radioactive molecules known as Radioimmunotherapy (RIT). These include Zevalin and Bexxar.

Targeted Therapy

New targeted agents include the proteasome inhibitor Velcade and mTor inhibitors such as temsirolimus.

Drug Regimen

  • Induction therapy
  • Aggressive therapy
  • Less aggressive therapy
  • Drug Regimen: Bendamustine PLUS Rituximab
  • Drug Regimen: CHOP PLUS Rituximab followed by consolidation with rituximab maintenance (375 mg/m2every 8 weeks until progression)
  • Drug Regimen: Cladribine PLUS Rituximab
  • Drug Regimen: Modified rituximab-Hyper CVAD with rituximab maintenanace in patients older than 65 years
  • First-line Consolidation
  • Drug Regimen: High dose therapy with autologous stem cell rescue
  • Second-line therapy
  • Second-line Consolidation
  • Drug Regimen: Allogenic stem cell transplant

References

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