Download Mantle Cell Lymphoma: Relapsed/Refractory

Mantle Cell Lymphoma: Relapsed/Refractory
Overview
MCL is R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincris-
Mantle cell lymphoma (MCL) is an uncommon form of non-Hodg-
tine , prednisone).
kin lymphoma (NHL), constituting about 6 percent of all NHL cases
Supplementing HyperCVAD-MTX/AraC (hyper-fractionated cy-
in the United States (approximately 3,000 cases per year). It is con-
clophosphamide,
sidered an aggressive B-cell lymphoma that usually affects men
methotrexate, cytarabine) with rituximab (Rituxan) or stem cell
between the ages of 50 and 70.
transplantation has also shown promising results. Although this
Much like other cancers, MCL may return after treatment. For those
treatment regimen is very intensive, with considerable toxicities, it
patients who become refractory (disease does not respond to
may provide longer response durations for selected younger pa-
treatment) or relapse (disease returns after treatment), secondary
tients with MCL than R-CHOP.
therapies may be successful in providing another remission.
If R-CHOP or R-HyperCVAD are used as front-line therapy, they are
It is critical to remember that today’s science is moving very fast and
generally not used again (second-line therapy) due to the limits on
that treatment advances are continuously being made. Therefore,
the cumulative amount of doxorubicin that can be tolerated by the
information regarding the clinical trials or treatments listed in this
heart.
fact sheet may not be entirely up to date depending on when this
Bendamustine (Treanda) is an agent that damages a cancer cell’s
information is being read. Patients should contact the Lymphoma
DNA, ultimately resulting in cell death. It has received FDA approval
Research Foundation or speak with their physician for potential
for the treatment of indolent (slow-growing) B-cell NHL that has not
treatment updates.
responded to rituximab (Rituxan) and for the treatment of chronic
Treatment Options
lymphocytic leukemia (CLL). Researchers are currently investigat-
Like other forms of NHL, there is no consensus on the best treatment for relapsed or refractory MCL. However, there are a number
vincristine,
doxorubicin,
dexamethasone,
ing the combination of bendamustine (Treanda) and rituximab
(Rituxan) on relapsed or refractory MCL in clinical trials.
of treatment options available for these patients. The type of
Another phase II chemotherapeutic clinical trial under investigation
treatment prescribed for an individual depends on several factors,
for relapsed or refractory MCL is RT-PEPC (rituximab, thalidomide,
including when the relapse occurs, the patient’s age, extent of dis-
prednisone, etoposide, procarbazine, cyclophosphamide).
ease, overall health and prior therapies received.
Immunotherapy: Several clinical studies are investigating the ef-
Proteosome inhibitor: Bortezomib (Velcade) is a proteosome in-
fectiveness of immunotherapy, in which the power of the immune
hibitor that has been approved by the United States Food and Drug
system is used to fight cancer.
Administration (FDA) for the treatment of MCL patients who have
Monoclonal antibodies, such as rituximab (Rituxan), are a form of
received at least one prior therapy. Proteosome inhibitors disrupt
immunotherapy. They work by attaching themselves to specific
a molecular pathway that is critical for the elimination of proteins
protein targets on the surface of lymphoma cells, triggering the pa-
in both normal and cancer cells. Recent studies with bortezomib
tient’s immune system to locate and kill the cancer cells. Rituximab
(Velcade) have demonstrated that the drug complements many
(Rituxan) has been successfully combined with numerous cancer
conventional chemotherapy agents.
treatments, including chemotherapy, as described above. Research
Chemotherapy: Recent studies have shown that combining che-
is now taking place to measure the benefits of receiving rituximab
motherapy regimens with rituximab (Rituxan) improves MCL
(Rituxan) for an extended period of time following chemotherapy
patients’ response rates and possibly overall survival. A common
(also called rituximab maintenance) to ensure that MCL does not
chemotherapeutic treatment approach that has been used to treat
return.
Radioimmunotherapy (RIT) is a modification of the monoclonal antibody approach, in which a radioactive molecule is attached to the monoclonal antibody. After the monoclonal antibody attaches to
the cancer cell, radiation from the radioactive molecule destroys it. Two RIT drugs, Iodine-l3l tosituNational Headquarters
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New York, NY 10006
(212) 349-2910
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momab (Bexxar) and Yttrium-90 ibritumomab tiuxetan (Zevalin), have been approved to treat some
Helpline:(800) 500-9976
[email protected]
Immunomodulatory drugs (IMiDs): These drugs activate the patient’s immune system to mount
Website: lymphoma.org
Email:[email protected]
der investigation for relapsed and refractory MCL include lenalidomide (Revlimid) and thalidomide
types of NHL and are currently being tested against MCL. For example, a clinical trial is currently
evaluating the effectiveness of administering fludarabine, mitoxantrone and rituximab (Rituxan) followed by Yttrium-90 ibritumomab tiuxetan (Zevalin) on relapsed or refractory MCL patients.
an immune response against the cancer cells inside the patient’s body. Some IMiDs currently un(Thalomid). For example, a phase II clinical trial is currently investigating the effects of combining
lenalidomide (Revlimid), bortezomib (Velcade) and rituximab (Rituxan). A phase III clinical trial is also
The Lymphoma Research Foundation
offers the following patient education and
support programs:
testing lenalidomide (Revlimid) as a maintenance therapy.
mTOR (mammalian target of rapamycin) inhibitors: Excessive activation of the mTOR pathway can
lead to excessive cell growth, while inhibition of mTOR can prevent cell growth and even cause cell
•
Lymphoma Helpline
•
Clinical Trials Information Service
•
Lymphoma Support Network
(Everolimus), which is being tested in MCL patients refractory or intolerant to bortezomib (Velcade).
•
Publications
•
Teleconferences
Antimetabolites: These drugs interfere with cell growth. Gemcitabine (Gemzar) is an antimetabo-
•
Webcasts & podcasts
•
In-person conferences
death. Two mTOR inhibitors currently under investigation are temsirolimus (Torisel) and RAD001
lite currently being tested in newly diagnosed, relapsed or chemotherapy-resistant MCL patients.
Gemcitabine (Gemzar) is also being studied in combination with bortezomib (Velcade). Researchers
believe that bortezomib (Velcade) may make cancer cells more sensitive to gemcitabine (Gemzar).
PI3K delta inhibitor: CAL101 is a drug that prevents the growth and survival of tumor cells by target-
Medical reviewer:
ing a specific molecular pathway called the PI3 kinase signaling pathway. The drug is in very early
Oliver W. Press, MD, PhD
clinical trials, but appears to have very promising activity.
Fred Hutchinson Cancer Research Center
Supported through grants from:
Transplantation: Bone marrow contains immature stem cells that develop into red blood cells,
white blood cells and platelets. If very high doses of chemotherapy or radiation are used to
destroy cancer cells, normal bone marrow is destroyed. A stem cell transplant (SCT) can help
restore healthy bone marrow. There are two types of SCTs: allogeneic, in which patients receive
stem cells from another person, and autologous, in which patients receive their own cells.
Reduced-intensity transplants (also called non-myeloablative or mini-transplants) are procedures in which stem cells are received from an allogeneic donor, but the chemotherapy and/or
radiation administered prior to the transplant is less intense (i.e., just enough to allow the body
to accept the donor cells). Patients receiving reduced-intensity transplants may avoid some of
the side effects seen with high-dose chemotherapy coupled with SCT.
Debate exists among researchers regarding which type of transplant (e.g., autologous versus
allogeneic) is most efficacious and when transplant should be used in the treatment of MCL.
High-dose chemotherapy coupled with SCT can be used to treat MCL patients who have failed
©2010 Lymphoma Research Foundation
Getting the Facts is published by the
Lymphoma Research Foundation (LRF) for the
purpose of informing and educating readers.
Because each person’s body and response to
treatment is different, no individual should
self-diagnose or embark upon any course of
medical treatment without first consulting
with his or her physician. LRF is not
responsible for the medical care or treatment
of any individual.
Last Updated June 2010
initial chemotherapy but are responsive to a second chemotherapy regimen. Some researchers feel that allogeneic SCT is better for patients who have had a relapse and that autologous
SCT should only be used to treat patients as part of initial therapy.
Participating in Clinical Trials
Clinical trials are crucial for identifying effective drugs for lymphoma patients. Patients interested in participating in a clinical trial should talk to their physician. Contact the Lymphoma
Research Foundation’s Helpline for an individualized clinical trial search by calling (800) 5009976 or emailing [email protected].