The Treatment Journey for Some Lymphoma Patients
- Rock singer Ryan Hamilton’s diagnosis shifted from chronic lymphocytic leukemia to mantle cell lymphoma after further testing and a bone marrow biopsy, a change he called “more challenging.”
- Mantle cell lymphoma can range from slow‑growing to highly aggressive, making treatment complex; as Dr. Jakub Svoboda explains, it’s “a very heterogeneous group of diseases.”
- Hamilton has already begun chemotherapy, a regimen that often includes cytarabine paired with rituximab, and many patients receive aggressive treatment early, including autologous stem cell transplant.
- BTK inhibitors — including newer non‑covalent options like pirtobrutinib — are reshaping care for blood cancers; Dr. Kieron Dunleavy notes they “inhibit a key enzyme” essential for lymphoma cell survival.
One group of lymphomas affects B cells, infection-fighting white blood cells of the immune system. Mantle cell lymphoma is one of the B-cell lymphomas. It grows from B cells on the outer edge of the lymph node, called the mantle zone.
Read MoreHamilton called his new diagnosis more challenging, but his doctors call for a similar treatment plan.
Mantle Cell Lymphoma tends to be diagnosed at later stages, when it is widespread within the lymphatic system and involves other organs, such as the spleen and the bone marrow. It tends to progress more quickly than other lymphomas. These factors make it a challenge to treat.
Hamilton says in a Facebook post, “I’ve had a couple of rounds of chemo here in the hospital, which is doing what it needs to do.”
Most of the accepted chemotherapy regimens include a drug called cytarabine. It’s paired with rituximab (Rituxan), a monoclonal antibody that seeks out and targets a protein called CD20 on the surface of cancer cells.
Unlike with most other types of lymphoma, many cancer centers will treat mantle cell lymphoma with an autologous stem cell transplant when people are in their first remission, Dr. Svoboda says.
“So most patients with mantle cell lymphoma tend to get quite aggressive treatment early on.”
A stem cell transplant starts with very high doses of chemotherapy to get rid of as many cancer cells as possible. That’s followed by an infusion of your own stem cells, the young cells that grow into new blood cells to replace the ones chemotherapy damaged.
“I’ve spent most of my adult life making music and being supported by this incredible community of friends, fans, fellow artists, and wonderfully weird people all over the world. Today, I’m asking that community to rally around me in a different way,” Hamilton said in another Facebook post.
Treatments for Mantle Cell Lymphoma (MCL)
- High‑Dose Chemotherapy: Powerful drugs that kill fast‑growing cells, including cancer. Because they affect healthy cells too, they can cause intense side effects such as persistent nausea, vomiting, diarrhea, and constipation.
- Targeted Therapy: Treatments designed to attack specific vulnerabilities in cancer cells. BTK inhibitors like ibrutinib and duvelisib block the tyrosine kinase enzyme, a key driver in many lymphomas.
- Autologous Stem Cell Transplant (ASCT): Doctors collect a patient’s healthy stem cells, then use high‑dose chemotherapy to destroy diseased cells. The stored stem cells are infused back into the body to restore healthy blood cell production.
- Immunotherapy: Approaches that harness and strengthen the patient’s own immune system to recognize and fight cancer.
- Monoclonal Antibodies: Lab‑engineered proteins that latch onto specific targets on cancer cells. They can flag cancer cells for destruction by the immune system or block growth‑promoting signals that help the cancer thrive.
Expert Resources for CLL Patients
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- CLL is Not Considered Curable So Treatment May Resume Years Later
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- A Decade of Progress: New Targeted Treatments Are Redefining What’s Possible For People With CLL
- ‘The Eye of the Tiger’ — Why Mindset and Lifestyle are So Important During Treatment for CLL
- A Message for Caregivers: What to Know and When to Call for Help When Caring for CLL Patients
More on BTK Inhibitors During Treatment
Two classes of drugs have driven this shift in CLL treatment: BTK inhibitors and BCL-2 inhibitors. Both target specific molecular pathways that CLL and SLL cells depend on to survive, rather than broadly attacking all dividing cells the way chemotherapy does, which contributes to chemo’s notorious grueling side effects.
BTK inhibitors work by blocking Bruton’s tyrosine kinase, an enzyme that sits inside a signaling pathway that CLL and SLL cells rely on.
“They inhibit a key enzyme that’s involved in a critical pathway in CLL and SLL,” Dr. Kieron Dunleavy, who is a medical oncologist and hematologist who serves as section chief, Hematology, and disease group lead, Malignant Hematology, for MedStar Georgetown University Hospital at the Georgetown Lombardi Comprehensive Cancer Center, explains to SurvivorNet.
Shutting down that pathway is highly effective at controlling the disease.
Two Generations of BTK Inhibitors
The first BTK inhibitor to reach the clinic was ibrutinib (Imbruvica), followed by additional drugs in the same category. These earlier drugs are known as covalent BTK inhibitors, meaning they bind permanently to the BTK enzyme. They remain widely used and highly effective in CLL and SLL.
More recently, a second type of BTK inhibitor — a non-covalent (or reversible) BTK inhibitor — has entered the treatment landscape. The first drug of this type approved for CLL/SLL is pirtobrutinib (Jaypirca).
Since it binds to BTK differently than the covalent drugs, it can remain effective even after a patient’s disease has stopped responding to an earlier-generation BTK inhibitor.
“It is a highly effective BTK inhibitor,” Dr. Dunleavy says of pirtobrutinib, describing it as “a new type of Bruton’s tyrosine kinase inhibitor that has very high activity in CLL and SLL.”
Dr. Kathryn A.F. Kline, a hematologist at the University of Maryland Greenebaum Comprehensive Cancer Center, outlines potential side effects from these targeted therapies and explains how to mitigate any potential discomfort.
“I certainly have some patients who take these drugs and really have no significant side effects, which is amazing,” Dr. Kline tells SurvivorNet.
What Are Common Side Effects of BTK Inhibitors?
Relatively common side effects, however, for some patients, according to Dr. Kline, include the following:
- elevated blood pressure
- irregular heartbeat
- bleeding or bruising
- nausea
- diarrhea
- rashes
- headaches
- joint pain
Managing Side Effects Over the Long Term
Most of these side effects will vary from patient to patient.
“Some patients’ blood pressure will go a little bit higher… headaches and joint pain, those often get better after the first couple of cycles [of taking the drugs],” Dr. Kline says.
Patients will be on these drugs, or a combination of these drugs with other medications, “Sometimes for several years, sometimes for many years,” Dr. Kline explains.
“The side effects tend to be not non-existent, but usually pretty manageable,” she adds, noting that patients may be prescribed something to “manage their high blood pressure” or “maybe some Tylenol for headaches.”
Overall, these are “drugs that people are able to stay on for a pretty long time and feel good while they’re taking them.”
It’s important to talk to your doctor early about the potential benefits of taking BTK inhibitors, which side effects to watch for, and what to do if you start experiencing any of them.
What Goes Into an Autologous Stem Cell Transplant
An autologous stem cell transplant is a transplant of cells from a person’s own body. Unlike in allogeneic transplants, where the cells come from a donor, there is no risk of the body rejecting the new cells.
Even though the cells come from the patient’s own body, the process isn’t as simple as just removing and reinjecting cells. The transplant process requires extensive preparation to ensure it achieves its goal of creating a new, healthy, cancer-free immune system.
WATCH: Better Understanding an Autologous Stem Cell Plant
“This involves testing your heart and lungs, liver and kidneys,” explains Dr. Caitlin Costello, a hematologist/oncologist at UC San Diego Health. The testing is generally done as an outpatient procedure, and once you’re approved for the transplant, your medical team will schedule the process.
Dr. Costello explains that the first steps involve revving up the body’s stem cell production so there will be enough to transplant. This process, also an outpatient procedure, involves a combination of drugs. It may involve chemotherapy as well as growth factors. The chemotherapy will likely be drugs that you’re familiar with already, having received them before as cancer treatment.
The purpose of the chemotherapy at this point is to destroy as many cancerous cells as possible before the transplant.
The growth factor “is to stimulate your bone marrow, your normal bone marrow, to make stem cells like it normally does. . . just in excess,” says Dr. Costello, explaining that the system has to go into overdrive to make extra cells for the transplant.
Finally, with preparation completed, it’s time for the actual transplant. This is not a surgical procedure. The cells are delivered through a special catheter or sometimes an IV in the arm.
“Then we connect you to a machine,” says Dr. Costello.
“It’s not unlike a dialysis machine, where blood comes out of your body through one arm and goes into the machine. The machine separates the stem cells from the rest of the blood, and then the stem cells are put back into your body.”
The Changing Treatment Landscape for CLL
Treatment for chronic lymphocytic leukemia (CLL) has changed significantly over the past decade, giving patients more options and improving outcomes.
Not everyone with CLL needs treatment right away. People without symptoms or other signs that the disease is becoming active may be monitored with regular visits and blood tests, an approach called active surveillance, or ‘watch and wait.’
WATCH: New Targeted Treatments Are Redefining What’s Possible For People With CLL
“About 10 years ago, we were depending on chemotherapy as a first-line treatment,” Dr. Omar Alkharabsheh, a medical oncologist with Orlando Health Cancer Institute who specializes in blood cancers, tells SurvivorNet.
“We learned from many clinical trials that the results of chemotherapy are much inferior to newer novel agents, especially in patients with mutations that predict a poor response to chemotherapy, especially 17p deletion and/or TP53.”
Since ibrutinib became available, additional targeted therapies have been developed, including a new generation of BTK inhibitors.
“Subsequently, we had several phase 3 trials looking into a second-generation oral therapy. We call them covalent BTK inhibitors that also have shown better results compared to chemoimmunotherapy combinations,” Dr. Alkharabsheh explains.
“We have another class of medications called BCL-2 inhibitors, such as venetoclax, that, in combination with a monoclonal antibody, showed better results compared to chemoimmunotherapy,” Dr. Alkharabsheh explains.
The treatment landscape continues to expand as researchers study and develop new combinations of these targeted therapies.
For patients with CLL, these advances mean treatment decisions can now be more individualized. Factors such as the genetic characteristics of the CLL, overall health, and treatment goals can help guide discussions between patients and their doctors about which approach may be appropriate.
Questions To Ask Your Doctor
- Do I need treatment now, or is active surveillance appropriate?
- Is there a targeted treatment combination you recommend in my case?
- What side effects should I look out for?
- How will I be monitored while I am undergoing treatment?
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