Mantle cell lymphoma is an aggressive variety of lymphoma which is typically found in the lymph nodes, spleen, marrow and blood. It is unique in that it is classified as an aggressive variety of lymphoma and yet it sometimes behaves as an indolent lymphoma. Most typically it behaves aggressively and is more difficult to treat than other indolent lymphomas.
Mantle cell lymphoma is called that because it usually infiltrates the Mantle Zone of the lymph nodes. That is the area surrounding the lymphoid follicles. When it remains in the mantle zone it generally follows a more indolent course. When it spreads outside this area, in a more diffuse growth pattern, its behaviour becomes less indolent and more aggressive.
It is typically characterized by the expression of CD5, over expression of Cyclin D1 and the t(11:14) chromosomal translocation.
Historically mantle cell lymphoma has had a much poorer prognosis than other types of lymphoma, with a median survival of only 3-5 years. Newer chemotherapy protocols, and stem cell transplants have made marked improvements in survival. In the era of Rituximab the median survival has improved significantly and many studies report median survival of over 7 years.
Recent discoveries have shown that the most important prognostic factor is the proliferation index as measured by the MIB-1 and Ki-67 expression. Those patients with a proliferation index below 30% have a dramatically higher survival rate. After 5 years disease free, relapses in this population group are rare and a very high percentage of patients are in this group. Those with a proliferation index above 30% generally have a much poorer prognosis. The link below will take you to a virtual education video that reviews the prognosis, and treatment of mantle cell lymphoma, the role of the proliferation index, and the prospect of a cure. (1)
Here is a somewhat technical review of the diagnosis and bio-pathology of mantle cell lymphoma from Haematologicia.
Mantle cell lymphoma is generally treated as an aggressive type of NHL and aggressive combination chemotherapy is used. Nevertheless in some selected cases it presents as an indolent lymphoma and watch and wait may be appropriate in these cases.
Historically R-CHOP or R-HyperCVAD have been the primary first line of treatment. Studies seemed to indicate that R-HyperCVAD had a slight advantage in terms of remission rates and duration of remission. Proceeding directly to an autologous stem cell transplant produces even better results, and is being done more frequently. (2) More recently it has been found that ARA-C adds a significant benefit to the progression free survival. (3) (4)
Bendamustine is beginning to show some excellent results, just as is does with follicular lymphoma. It is perhaps a bit too early to say we should abandon R-CHOP or R-HyperCVAD in favour of Bendamustine but that may turn out to be what happens in the future. An early study from the Journal of Clinical Oncology has shown some impressive results with a Bendamustine combination. (5)
Another treatment which is showing promising early results is the combination of Lenalidomide and Rituxan. More follow up from this study is needed, but it had an initial response rate of 92% with 64% complete response rate. The 2 year overall survival was 97% (13)
The following is a single page chart reviewing the opinions of 10 of the foremost experts in treating mantle cell lymphoma. It asks each expert to answer the 4 questions below, and their opinions are presented in a chart. Just hover over the question for each doctor to read their answer.
Ibrutinib, which is known as a Bruton's Tyrosine Kinase Inhibitor has been showing some very promising results for mantle cell lymphoma, especially in patients who have failed other therapies. (6) Even when used as a single agent treatment the results are very promising (7) While a great more study needs to be done, Ibrutinib appears to be one of the more promising new agents on the market. In November of 2013 Ibrutinib was granted accelerated approval by the Food and Drug Administration in the USA based on the very promising results it has shown. (8)
Due to the fact that Mantle cell lymphoma generally has a worse prognosis than other aggressive types of NHL, consolidation therapy is strongly indicated. Consolidation simply means that as soon as the primary therapy is completed another therapy is initiated in order to "consolidate" the response in order to attempt to achieve a complete remission that is very durable. The most common form of consolidation therapy for most of the indolent types of lymphoma is maintenance Rituxan. It has also been shown that maintenance Rituxan dramatically improves the overall survival and progression free survival for mantle cell lymphoma patients. (9)
Two other types of consolidation therapy are common. A stem cell transplant for those who are eligible, and radioimmunotherapy such as Zevalin or Bexxar. Both options provide a survival benefit when compared to no consolidation therapy. (10)
Stem cell transplants are often used, either for as consolidation therapy as noted above, or for relapsed MCL. (14) This is becoming more common as results from studies show it offers a good opportunity for long term survival. Using an SCT with in-vivo Rituxan purging has been shown to have a 70% overall survival at 6 years (11) which is a remarkable improvement over past options.
Nevertheless stem cell transplants are a very aggressive approach and may not be necessary as newer more effective treatments have been developed in the past decade, including Bortezomib, and Ibrutinib. Therefore there is no complete consensus amongst experts about the best use of stem cell transplants (12)
For an excellent review of treating mantle cell lymphoma the the article below is a very detailed review from Oncolink. A must read for anyone with MCL.
For another detailed look at Mantle Cell Lymphoma visit the first link. Additional information is provided at the other links as well.
Alternating Courses of 3x CHOP and 3x DHAP Plus Rituximab Followed by a High Dose ARA-C Containing Myeloablative Regimen and Autologous Stem Cell Transplantation (ASCT) Is Superior to 6 Courses CHOP Plus Rituximab Followed by Myeloablative Radiochemotherapy and ASCT In Mantle Cell Lymphoma: Results of the MCL Younger Trial of the European Mantle Cell Lymphoma Network
Interim Results of an International, Multicenter, Phase 2 Study of Bruton’s Tyrosine Kinase (BTK) Inhibitor, Ibrutinib (PCI-32765), in Relapsed or Refractory Mantle Cell Lymphoma (MCL): Durable Efficacy and Tolerability with Longer Follow-up
A peer review of the above study: Is Early Hematopoietic Stem-Cell Transplantation Necessary in Mantle-Cell Lymphoma?