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Post details: MCL Article by Dr Goy

02/24/13

Permalink 06:40:46 am, Categories: Treatments, 1323 words   English (US)

MCL Article by Dr Goy

A Conversation About Mantle Cell Lymphoma with Dr. Andre Goy
Chairman and Director of the John Theurer Cancer Center at Hackensack University Medical Center

http://www.focusonmcl.org/content/conversation-about-mantle-cell-lymphoma-dr-andre-goy

Would you describe mantle cell lymphoma?

Mantle cell lymphoma (MCL), which was only officially designated as a separate entity in 1994, is not a common subtype of non-Hodgkin lymphoma (NHL); it represents only about six percent of NHL. MCL often has characteristics of both indolent and aggressive forms of NHL. MCL can have a rather indolent course during which most patients have limited symptoms; however, most patients relapse and become chemoresistant over time. Such challenges have led to a lot a great deal of innovation over the last twenty years resulting in significant improvement in outcomes.

Patients with MCL typically present with lymph node enlargement, an enlarged spleen, elevated white blood cell counts, and almost all patients have gastrointestinal and bone marrow involvement. However, only one-third of the patients at diagnosis have lymphoma-related symptoms (i.e., fevers and night sweats, weight loss). The diagnosis of MCL is made through pathology testing which shows characteristic morphology, immunophenotype (i.e., cells expressing B-cell mature markers CD19, CD20, and co-expressing a T-cell marker CD5 while MCL cells are found to be CD10 and CD23-negative) and typically requires evidence of overexpression of cyclin D1 or t(11;14) gene translocation.

How is MCL typically treated?

The treatment of MCL has evolved dramatically over the last two decades. Therapy is selected based on whether patients are eligible for intensive therapy based on their clinical presentation and age, given that the median age of diagnosis is the mid to late sixties.

Patients who are eligible for intensive strategies can receive either classic Hyper-CVAD (cyclophosphamide, vincristine, doxorubicin, and dexamethasone) + rituximab (Rituxan) alternating with cytarabine and methotrexate or induction therapy followed by autologous stem cell transplants as consolidation therapy. This approach has led to a dramatic improvement of median progression-free survival (PFS) in excess of five years versus 18 to 24 months with standard R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone).

For patients who are older or have other conditions that would prevent dose-intensive strategies, there is a far more effective therapy than R-CHOP alone. Recent data looking at maintenance rituximab post-induction with R-CHOP show a clear improvement over R-CHOP alone, setting a new standard. In addition bendamustine (Treando) + rituximab which was compared to R-CHOP as frontline treatment as part of the Study Group Indolent Lymphomas (StiL) trial has shown significant improvement in PFS, although there was no difference in overall survival. The reported toxicity profile also makes it an appealing option in MCL. The difference in PFS was not observed in patients with follicular lymphoma in the same trial.

There are also a number of novel therapies being developed in the relapsed/refractory setting. These agents are currently being investigated for integration in frontline treatment regimens, in combination with chemotherapy, or as maintenance.

What are the main areas of research in MCL?

Though the results for frontline have clearly improved in MCL, most patients still relapse and become chemoresistant over time. There are two main topics for MCL research: (1) a number of new biological agents are rapidly changing the horizon for MCL treatment, especially with this disease which patients typically respond poorly with chemotherapy, and (2) a better understanding of the biology of MCL, especially a growing awareness of the impressive heterogeneity among patients, which might help stratify patients better for treatment in the future.

Regarding novel therapies, bortezomib (Velcade) became the first U.S. Food and Drug Administration-approved drug ever in relapsed/refractory MCL and is currently being tested as part of induction strategies with chemoimmunotherapy regimens. In the European Union (EU), temsirolimus (Torisel) is the only drug approved in relapsed/refractory MCL. Recently, a number of very exciting compounds have emerged in MCL, such as lenalidomide (Revlimid) and ibrutinib. In a study of patients who were previously treated (median of four prior therapies, range two-ten), treatment with lenalidomide resulted in a response rate of 29 percent with durable benefit shown by a median duration of response in excess of sixteen months, which is really impressive in that setting.

Ibrutinib, a BTK inhibitor that targets the B-cell receptor signaling pathway, has shown response rates of 60 percent to 70 percent in patients with MCL, with a complete response rate of 20 percent, a rate that appears to increase over time. Lenalidomide and ibrutinib, both oral compounds, have very easy toxicity profiles and are good candidates for integration in frontline treatment regimens.

Regarding the progress made in understanding the biology of MCL, our goal is to identify better predictive markers of MCL. There are a number of prognostic factors that have been reported in MCL that can help physicians to some extent predict the outcome among patients. Yet, none of these factors help physicians make a decision for an individual patient. Mounting evidence suggests a great heterogeneity among MCL patients (with similar clinical features) as illustrated by gene expression profiling studies (proliferation signature) and a number of other technological approaches. Practically, there are 5 percent to 10 percent of patients with MCL who have a very low-grade indolent course; they have high white blood cell counts, an enlarged spleen, and few or no enlarged lymph nodes. These patients are much more clinically and genetically stable (ie, they have much fewer secondary abnormalities) than patients with more aggressive disease. Patients with low-grade indolent disease are generally monitored and treated differently than patients with more aggressive MCL and are likely not enrolled in standard clinical trials. Patients with aggressive, or “classic MCL” are usually treated as intensively as possible to achieve a deep response, which translates into a better outcome. Achieving a complete remission (CR), and even better, a molecular CR appears to be critical, and this endpoint is being investigated in upcoming EU trials.

Please discuss the importance of clinical trials, and if are there any specific trials you wish to address?

The great improvement of outcomes in MCL over the past twenty years is a great example of the impact of clinical trials. Because MCL is such a challenging disease to treat, both physicians and the medical community at large, as well as patients, have been more willing to try novel options, which is why we have made so much progress in MCL. With the number of exciting options and novel therapies, it is becoming even more critical for physicians to encourage patients to participate in clinical trials. Current trials are investigating the use of novel agents either in combination or as maintenance post-conventional therapies to reduce the risk of relapse and for continued improvement our patients’ outcomes.

What advice would you give to a newly diagnosed patient?

Most newly diagnosed patients do not have a lot of symptoms, so it is really challenging for a patient to accept the idea that they need very intensive therapy. It is important for patients to look at all the treatment options including intense strategies that clearly lead to deeper responses which will likely translate into longer benefit. We are also developing non-chemotherapy approaches in older patients with more indolent MCL.

How are you involved with the Lymphoma Research Foundation and why would you recommend a patient become involved with the organization?

I am part of the Lymphoma Research Foundation’s Scientific Advisory Board and Mantle Cell Lymphoma Research Consortium. We have annual meetings where we discuss ongoing research and developing projects. This usually leads to a synopsis of the state-of-the art research and management for MCL that is published to give more information to patients. MCL is a disease for which there is a clear lack of consensus on treatment, and because it is such a heterogeneous and uncommon disease, it is hard for patients to really navigate their way once they are diagnosed. It is important for patients to have an objective synopsis of the changing landscape of MCL and how much progress has been made with regard to treatment.

Updated February 20, 2013

Comments:

Comment from: Impalafarmer [Visitor]
REAL nice. Let me be the first to post a comment that actually has to do with the subject. I was diagnosed with MCL in September of 2012 and found this blog in my research. I check in on it from time to time to see if the young man that's had a 6+ year remission as of last May has checked in again yet. I see Dr. Goy has given us an informative post so I read it through, then checked the comments to see nothing but annoying spam. Is anyone mediating this, at least checking in to weed this garbage out? I look to this blog for information, hope & inspiration. When I see this stupidity in the comments, not ONE single comment about the groundbreaking treatments Dr. Goy is talking about but just a big load of spam, it makes me want to give up treatment & die.
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Permalink 10/03/17 @ 20:53
Comment from: nbarwonderful [Member]
Permalink 10/07/17 @ 00:50
Comment from: nhelingdebr [Member]


Pandora Outlet 925 Silver Antique Angry Birds Charms Beads FJ283 - $28.00 : cheap pandora Jewelry, pandoraringscharm.top





















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Permalink 10/19/17 @ 01:26

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