Oncologists weigh in: The most exciting research into MCL treatment

By Linda Childers | Medically reviewed by Jeffrey A. Bubis, DO, FACOI, FACP
Published November 2, 2023

Key Takeaways

  • Mantle cell lymphoma (MCL) is a rare cancer accounting for 3%–7% of non-Hodgkin’s lymphoma cases in the US and Europe. 

  • Newer therapies, including CAR-T cell immunotherapy and non-covalent BTK inhibitors, have improved how MCL is treated when patients relapse. 

  • Advances in the treatment of MCL offer patients more options and improve the outlook for long-term survival. Clinical trials are currently underway to study potential improvements in MCL treatments.

Mantle cell lymphoma (MCL) is a form of B-cell non-Hodgkin’s lymphoma that typically occurs in middle-aged or older adults. Men are three times more likely than women to be diagnosed with MCL, and White individuals are twice as likely to be diagnosed than Black individuals.[] 

Historically, MCL has been considered hard to treat, but the good news, according to oncologists, is that new treatments for MCL have emerged and are continuing to develop in clinical trials.

Treatment potentials

Patients with MCL often don’t exhibit symptoms until the disease is advanced. Outcomes for treatment of MCL are not primarily associated with the stage of disease at diagnosis, according to Jeffrey A. Bubis, DO, FACOI, FACP, MDLinx medical advisory board member. Disease progression is easily assessed with a MIPI calculation, which doesn't include stage, and the primary drivers are pathologic features (ie, blastoid, pleomorphic histology) and cytogenetics. 

In addition, while many patients do well with initial MCL treatment, many tend to relapse. Variables that affect treatment response include age, performance status, and fitness for aggressive therapy, according to Dr. Bubis.

Expert perspective

“New treatments have improved chemotherapy regimens,” Marco Ruiz Andia, MD, Chief of HIV Oncology and HIV Stem Cell Transplantation with Miami Cancer Institute, tells MDLinx. “Today we can deliver more focused therapy with less side effects and maintenance strategies with longer periods of remission, without the need for treatment, resulting in a better quality of life.”

Dr. Ruiz-Andia notes the first line treatment for MCL depends on the stage of the disease, the patient’s age, overall health, and comorbidities.

The first-line treatment for MCL has traditionally been high doses of chemotherapy, followed by autologous stem-cell transplant (ASCT), but clinical trials in patients who do not have the indolent (slow-growing) form of the disease are examining how targeted therapies may replace the need for ASCT in some cases.

While MCL isn’t curable, treatment can put the disease into remission. Survival rates depend on whether MCL cases are aggressive or indolent.

The Leukemia & Lymphoma Society says several new treatments have been approved to treat relapsing MCL, including chemotherapy drugs bortezomib and lenalidomide, and BTK inhibitors acalabrutinib and zanubrutinib.[] The CAR-T cell therapy, brexucabtagene autoleucel, was accelerated for FDA approval in 2020 for use in relapsing cases of MCL. 

Treatment influenced by the pace of cancer growth

MCL is a very heterogeneous disease that can be nodal or leukemic, blastoid or smoldering, with treatment based accordingly. 

Peter Ledakis, MD, an oncologist with Mercy Medical Center in Baltimore, says he recommends a wait and watch approach for patients who have a slow-growing form of the disease and are asymptomatic.

He monitors patients through bloodwork every 2 to 3 months and performs an imaging test every 3 to 6 months. If tests show that a patient’s cancer has spread or their symptoms become worse, he suggests a treatment regimen.

“MCL patients do tend to relapse [and] become refractory,” Dr. Ledakis says. “In these cases, we’ll often prescribe BTK inhibitors that are oral pills a patient can take daily.” Dr. Bubis notes other acceptable therapies, such as salvage therapy with CAR-T, for example.

In addition to treating relapsing MCL, a recent study showed BTK inhibitors are a well-tolerated treatment for older patients who aren’t good candidates for chemo and ASCT.[]

New treatments continue to emerge in the fight against MCL. In January 2023, the FDA approved pirtobrutinib, the first non-covalent reversible BTK inhibitor. The Leukemia & Lymphoma Society says this new treatment works like the other BTK inhibitors by suppressing Bruton’s tyrosine kinase, which malignant B-cells need to grow. Unlike the other covalent BTK inhibitors, the newly approved drug causes fewer off-target side effects.[] 

Related: Managing cardiotoxicity of BTKi treatments

Clinical trials show promising results

A number of clinical trials are examining both first-line treatments for MCL and additional treatments for relapsing/refractory cases.

“The TRIANGLE trial attempts to answer the question of whether incorporating ibrutinib into frontline treatments could benefit younger patients, under 65, with stage II-IV MCL,” Dr. Ruiz-Andia says. 

Initial results from the phase 3 TRIANGLE trial showed that adding ibrutinib to the standard chemotherapy regimen could eliminate the need for ASCT in some younger, healthier MCL patients. The researchers noted more follow-up is needed.[]

Another trial, the SHINE trial, examined how a new combination of ibrutinib in combination with bendamustine plus rituximab and rituximab maintenance therapy was an effective first-line treatment for MCL patients over the age of 65 who weren’t good candidates for ASCT because of excessive treatment toxicities.[]

Dr. Ledakis says recent research has found that CAR T-cell therapy is also effective in treating patients with relapsing and refractory MCL. Although CAR T-cell therapy is a powerful treatment, Dr. Ledakis says it’s still not widely available for many patients who need it.

“CAR T-cell therapy is only offered at a limited number of CAR T-cell therapy centers across the country,” Dr. Ledakis says.

Treatment options vary from patient to patient, and they are not interchangeable. However, if your patient is a good candidate for BTK therapy, Dr. Ledakis stands behind their potential. “BTK inhibitors offer a safe, well-tolerated treatment that’s widely available and offers improved outcomes,” he says.

What this means for you

While progress has been made, clinical trials continue to examine how to improve both first-line treatment and relapsing/refractory treatments for MCL patients. Many of the clinical trials are reviewing how a combination of targeted therapies might be used to provide better outcomes and increase progression-free survival for patients.

Read Next: Looking forward: How far we’ve come with understanding BTKis

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