Lymphoma is one of the three main groups of blood cancers, alongside leukemia and multiple myeloma. Mantle cell lymphoma (MCL) is a rare type of lymphoma that accounts for about 6% of total diagnoses each year.
“Mantle cell lymphoma is one of the rarer forms of B cell non-Hodgkin lymphoma,” explains Tycel Phillips, M.D., a hematologist-oncologist and associate professor of lymphoma at City of Hope® Cancer Center Duarte. “Unfortunately, mantle cell lymphoma is not curative, meaning patients can expect to have sequential episodes of remissions and relapse. Our hope is always to have extended durations of remission.”
Until recently, chemotherapy has been the standard treatment choice for patients with MCL. But newer therapies and regimens developed in the past two years may offer MCL patients prolonged survival and an improved quality of life, even during periods of treatment.
“Our hope is that these newer, more tolerable treatment regimens will continue to improve tolerance, outcomes and maintain the durability of remissions noted with chemotherapy,” Dr. Phillips says.
This article on MCL covers the following topics:
- New treatments improve MCL care
- Chemotherapy and stem cell transplant: Benefits and side effects
- CAR T cell therapy: Benefits and side effects
- BTK inhibitors: Benefits and side effects
- Other chemo-free therapies in the pipeline
- Symptoms and diagnosis of MCL
- When to see a doctor
If you or a loved one has been diagnosed with lymphoma and are looking for a second opinion, call us 24/7 at 877-460-4673.
New Treatments Improve MCL Care
Mantle cell lymphoma is a rare, complex type of lymphoma that begins in an area of the lymph nodes known as the mantle zone. The mantle zone contains immature B cells — a type of immune cell that helps the body detect and fight infection or disease.
While MCL is generally considered a fast-growing type of cancer, it may develop differently depending on the patient. However, it tends to affect men more than women and is more common in people over 65.
While the most common conventional treatment regimen for MCL is a combination of several chemotherapy drugs, the U.S. Food and Drug Administration (FDA) has recently approved several new therapies, including:
- New chimeric antigen receptor (CAR) T cell therapies, which are cellular immunotherapies for patients with relapsed disease
- Bruton tyrosine kinase (BTK) inhibitors, a type of targeted therapy in both newly diagnosed and relapsed patients
- Bispecific antibodies, a type of immunotherapy that has been granted accelerated approval
Chemotherapy and Stem Cell Transplant: Benefits and Side Effects
Chemotherapy has been the cornerstone of treatment for MCL for decades. The most common combinations of chemo drugs used for mantle cell lymphoma are referred to as R-CHOP and BR, depending on which of the following medications it contains:
- Rituximab
- Cyclophosphamide doxorubicin
- Hydroxydaunomycin
- Oncovin
- Prednisone
- Bendamustine
In most cases, patients 65 and younger are treated with R-CHOP, alternating with another chemotherapy regimen that generally includes a drug called cytarabine. After this regimen, those in remission would routinely undergo a process called a stem cell transplant. This involves more chemotherapy followed by a stem cell rescue, which helps reconstitute their immune system.
“But many older patients couldn’t tolerate a stem cell transplant, so they would just receive treatment using R-CHOP or BR alone,” says Dr. Phillips. And, with new therapies now in the clinic, “we’ve shifted away from being solely dependent on chemotherapy in the last three years or so.”
While effective, chemotherapy for MCL is often intensive, causing side effects such as a weakened immune system, fatigue, nausea, digestive issues and hair loss.
CAR T Cell Therapy: Benefits and Side Effects
CAR T cell therapy is a type of treatment that involves collecting cancer-killing T cells from a patient’s body, engineering them in a lab so that they are better able to detect and fight cancer, then reinfusing them into a patient’s body.
CAR T cell therapy is most often used for mantle cell lymphoma that has come back or has not responded to other types of treatment, explains Dr. Phillips.
“We struggled for a long time to identify a regimen that would improve outcomes in patients whose disease progressed even while they were taking BTK inhibitors — and that's where CAR T cell therapy came into play.”
Studies have shown that patients who did not respond to BTK inhibitors saw substantial improvement when treated with either of two recently approved CAR T cell therapy agents, brexucabtagene autoleucel (brexu-cel) or lisocabtagene maraleucel (liso-cel).
CAR T cell treatment is a single treatment with a markedly different toxicity profile than conventional chemotherapy for MCL, while offering longer periods of remission in this difficult-to-treat space.
BTK Inhibitors: Benefits and Side Effects
BTK inhibitors are a group of targeted therapies that work by “turning off” a survival signal that helps mantle lymphoma cancer cells continue to grow. While they have been used before as a secondary treatment after chemo, two BTK inhibitors — acalabrutinib and ibrutinib — are now being offered as a first-line therapy for MCL, based on the findings of two recent studies, one that was global and one developed in Germany.
One study found that patients over 65 who were treated with chemotherapy plus the BTK inhibitor acalabrutinib had longer periods of progression-free survival, which is the amount of time a patient lives with a disease without his or her symptoms getting worse.
A second study showed that younger patients who underwent R-CHOP alternating with R-DHAP, combined with the BTK inhibitor ibrutinib, had better outcomes than the standard of care regimen, which was R-CHOP/R-DHAP followed by a stem cell transplant. Researchers found that by adding ibrutinib, there was no benefit to the addition of a stem cell transplant.
According to Dr. Phillips, “this suggests there’s no reason to use stem cell transplantation in most patients who are given ibrutinib during the induction regimen and two years of ibrutinib maintenance therapy after that.”
This is good news for patients who are not well-suited to stem cell transplant or intensive chemotherapy.
“Removing that treatment from our patient algorithm invariably improves patient outcomes, keeps patients out of the hospital and reduces late toxicities,” says Dr. Phillips.
Other Chemo-Free Therapies in the Pipeline
Research and clinical trials into a wide range of other treatments and treatment combinations are underway, focusing on options such as:
- New BTK inhibitors
- BCL2 inhibitors, another type of immunotherapy
- Chemotherapy-free treatment regimens using a combination of other medications
Some of these studies show excellent promise, particularly for older patients and those in higher-risk groups.
City of Hope is also conducting leading-edge research into other potential MCL treatments using an immunotherapy called bispecific antibodies. During this therapy, antibodies are infused into the patient’s body, where they bind to a patient’s T cells and direct them toward the patient’s cancer.
“Our institution has led the field in the development of bispecific antibodies for mantle cell lymphoma,” Dr. Phillips says. And while the two most commonly used bispecific antibody regimens are not yet approved by the FDA, they have both been vetted as safe and effective for use by the National Comprehensive Cancer Center, based on studies led by City of Hope investigators.
Symptoms and Diagnosis of MCL
There are several different types of mantle cell lymphoma. Some patients may experience no symptoms of the disease, or only experience symptoms when it has reached an advanced stage. Some common signs and symptoms of MCL include:
- Swelling in the armpit, groin or neck
- Nausea, bloating or diarrhea
- Fever
- Fatigue
- A loss of appetite or unexpected weight loss
While doctors don’t yet know exactly why some people develop MCL, there are a few known risk factors, such as:
- Being male
- Being over 65 years old
- Being of white or Caucasian race or ethnicity
When to See a Doctor
Mantle cell lymphoma is rare and complex and it may be difficult to treat. Specialized or newer therapies for MCL are often only available at institutions like City of Hope, where clinical providers and researchers work side by side to develop and trial new cancer treatments.
“We have a lot of expertise in this area and we'll continue to drive research that will hopefully get us to the point where we can cure this disease,” Dr. Phillips says.
“If we can buy patients time, we're buying them more options and newer treatments that will eventually help us overcome this disease.”
If you or a loved one has been diagnosed with lymphoma and are looking for a second opinion, call us 24/7 at 877-460-4673.