Mantle cell lymphoma medical therapy: Difference between revisions
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==Overview== | ==Overview== | ||
The predominant therapy for mantle cell lymphoma is [[chemotherapy]]. Adjunctive | The predominant therapy for mantle cell lymphoma is [[chemotherapy]]. Adjunctive immune based therapy, [[radioimmunotherapy]], and new biologic agents may be required. | ||
==Medical Therapy== | ==Medical Therapy== | ||
There are no proven standards of treatment for mantle cell lymphoma, 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 no proven standards of treatment for mantle cell lymphoma, 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. | ||
| Line 12: | Line 12: | ||
:* [[Chemotherapy]] | :* [[Chemotherapy]] | ||
:* | :* Immune based therapy | ||
:* [[Radioimmunotherapy]] | :* [[Radioimmunotherapy]] | ||
| Line 27: | Line 27: | ||
[[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. | [[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]] ([[cyclophosphamide]], [[doxorubicin]], [[vincristine]], and [[prednisone]]) with [[rituximab]] (Rituxan, Mabthera) is the most common chemotherapy, and often given as outpatient by IV. | :* For frontline treatment, [[CHOP]] ([[cyclophosphamide]], [[doxorubicin]], [[vincristine]], and [[prednisone]]) with [[rituximab]] (Rituxan, Mabthera) is the most common chemotherapy, and often given as outpatient by IV. | ||
:* Hyper-CVAD chemotherapy consists of two combinations of drugs (courses A and B) given in an alternating fashion. The term 'hyper' refers to the hyperfractionated nature of the chemotherapy, which is given in smaller doses, more frequently, to minimize side effects. 'CVAD' is the acronym of the drugs used in course A: [[cyclophosphamide]], [[vincristine]], [[doxorubicin]] (also known by its trade name, Adriamycin), and [[dexamethasone]]. Course B consists of [[methotrexate]] and [[cytarabine]]. 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 microglobulin blood test was normal. It is showing better complete remissions (CR) and progression free survival (PFS) than CHOP regimens. | |||
:* Hyper-CVAD chemotherapy consists of two combinations of drugs (courses A and B) given in an alternating fashion. The term 'hyper' refers to the hyperfractionated nature of the chemotherapy, which is given in smaller doses, more frequently, to minimize side effects. 'CVAD' is the acronym of the drugs used in course A: [[cyclophosphamide]], [[vincristine]], [[doxorubicin]] (also known by its trade name, Adriamycin), and [[dexamethasone]]. Course B consists of [[methotrexate]] and [[cytarabine]]. 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 | |||
:* Another chemotherapy class is [[fludarabine]] monotherapy, sometimes combined with [[cyclophosphamide]] and mitoxatrone, usually with rituximab. | :* 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 mantle cell lymphoma. | :* [[Cladribine]] and [[Clofarabine]] are two other drugs being investigated in mantle cell lymphoma. | ||
:* Cytotoxic chemotherapies, including bendamustin, are being studied alone and with similar combinations. | :* 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 of[[prednisone]], [[etoposide]], [[procarbazine]], and [[cyclophosphamide]], taken orally, has proven effective for relapsed patients[http://www.asco.org/ASCO/Abstracts+&+Virtual+Meeting/Abstracts?&vmview=abst_detail_view&confID=23&abstractID=104642]. | :* A relatively new regimen that uses old drugs is PEP-C, which includes relatively small, daily doses of [[prednisone]], [[etoposide]], [[procarbazine]], and [[cyclophosphamide]], taken orally, has proven effective for relapsed patients[http://www.asco.org/ASCO/Abstracts+&+Virtual+Meeting/Abstracts?&vmview=abst_detail_view&confID=23&abstractID=104642]. | ||
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). | 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=== | ===Immunotherapy=== | ||
[[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 mantle cell lymphoma 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]]. | [[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 mantle cell lymphoma 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=== | ===Targeted Therapy=== | ||
New targeted agents include the proteasome inhibitor [[Velcade]] and mTor (mammalian target of rapamycin) inhibitors such as [[Torisel|temsirolimus]]. | New targeted agents include the proteasome inhibitor [[Velcade]] and mTor (mammalian target of rapamycin) inhibitors such as [[Torisel|temsirolimus]]. | ||
==References== | ==References== | ||
{{Reflist|2}} | {{Reflist|2}} | ||
Revision as of 18:03, 2 September 2015
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sowminya Arikapudi, M.B,B.S. [2]
Overview
The predominant therapy for mantle cell lymphoma is chemotherapy. Adjunctive immune based therapy, radioimmunotherapy, and new biologic agents may be required.
Medical Therapy
There are no proven standards of treatment for mantle cell lymphoma, 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:
- Immune based therapy
- New biologic agents
- The phases of treatment are generally:
- Frontline
- Following diagnosis
- Consolidation
- After frontline response (to prolong remissions)
- 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 (cyclophosphamide, doxorubicin, vincristine, and prednisone) with rituximab (Rituxan, Mabthera) is the most common chemotherapy, and often given as outpatient by IV.
- Hyper-CVAD chemotherapy consists of two combinations of drugs (courses A and B) given in an alternating fashion. The term 'hyper' refers to the hyperfractionated nature of the chemotherapy, which is given in smaller doses, more frequently, to minimize side effects. 'CVAD' is the acronym of the drugs used in course A: cyclophosphamide, vincristine, doxorubicin (also known by its trade name, Adriamycin), and dexamethasone. Course B consists of methotrexate and cytarabine. 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 microglobulin 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 mantle cell lymphoma.
- 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 of prednisone, etoposide, procarbazine, and cyclophosphamide, taken orally, has proven effective for relapsed patients[3].
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 mantle cell lymphoma 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 (mammalian target of rapamycin) inhibitors such as temsirolimus.