Zachary Epstein-Peterson, MD, attending physician, Memorial Sloan Kettering Cancer Center, discusses the use of CAR T-cell therapy in mantle cell lymphoma (MCL) and highlights questions that remain to be answered within the treatment landscape.

Clinicians and patients alike are in a golden age of therapy for treating patients with MCL, Epstein-Peterson begins. However, historically, the outcomes for patients with the disease are very poor, specifically in patients with relapsed/refractory disease, Epstein-Peterson notes, adding that despite this, there are now many new tools in a treating clinician’s treatment armamentarium, most of which he says are effective and tolerable. Overall, it is a promising time to help care for patients with the disease and assist in pioneering new treatments for the future, Epstein-Peterson adds.

Looking to the future of beneficial treatments for this patient population, the landscape is likely to include CAR T-cell therapies, Epstein-Peterson continues. CAR T cells are firmly established in the care of patients with diffuse large B-cell lymphoma, but not as much in the care of patients with MCL, Epstein-Peterson adds. Based on the data seen from treatment with brexucabtagene autoleucel (brexu-cel; Tecartus) and lisocabtagene maraleucel (liso-cel; Breyanzi), these therapies work well in treating patients with MCL, though there are differing toxicity profiles between the 2 regimens. Despite the associated adverse events, the therapies remain manageable, Epstein-Peterson notes.

It remains vital to be aware of cytokine release syndrome and of neurotoxicity in patients, though this does not deter from the agents’ efficacy, Epstein-Peterson adds. Investigators will continue to investigate the optimal patient population to be treated with CAR T-cell therapies and how the CAR T-cell treatments can be best sequenced with one another in the relapsed/refractory setting, Epstein-Peterson explains. Ultimately, clinicians will need to address toxicities more effectively moving forward, but the data from CAR T-cell therapy to date in MCL are encouraging, Epstein-Peterson concludes.

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Zachary Epstein-Peterson, MD, discusses the use of CAR T-cell therapy in mantle cell lymphoma and highlights questions that remain to be answered within the treatment landscape.


Dr Epstein-Peterson on the Use of CAR T-Cell Therapy in MCL

Zachary Epstein-Peterson, MD, attending physician, Memorial Sloan Kettering Cancer Center, discusses available treatment approaches for patients with mantle cell lymphoma (MCL) who are both transplant eligible and ineligible.

Patients with MCL who are transplant eligible traditionally tend to be younger, have high performance status, and display fewer comorbid conditions, according to Epstein-Peterson; these patients do not typically harbor 

 mutations. Recent advancements in the treatment landscape of MCL have allowed for patients up to 65 years of age to undergo autologous stem cell transplantation (ASCT), Epstein-Peterson says.

Although cytarabine and high-dose therapy may be considered for these patients, the majority will receive induction therapy with rituximab (Rituxan) and cytarabine-based chemoimmunotherapy, Epstein-Peterson notes. Rituximab, dexamethasone, cytarabine, and oxaliplatin (R-DHAX ) is the most common choice of therapy, he specifies. Once these patients begin to show chemosensitivity, they will be referred to ASCT. This is followed by high-dose therapy and autologous stem cell rescue, and rituximab maintenance therapy will be considered, Epstein-Peterson explains.

Unlike transplant-eligible patients, ineligible patients are a more heterogeneous population, Epstein-Peterson adds. Several viable options exist for these patients. The most prescribed frontline regimen for patients aged 65 or older who are transplant ineligible is bendamustine plus rituximab (BR) followed by rituximab maintenance therapy, Epstein-Peterson notes.

Another viable option is the combination of rituximab and lenalidomide (Revlimid). This option is advantageous for patients who hope to avoid intensive chemotherapy or reduce the time spent in the hospital, Epstein-Peterson says. In previous research, this regimen has been shown to elicit favorable response rates, duration of response, and progression-free survival, Epstein-Peterson concludes.

Zachary Epstein-Peterson, MD, discusses available treatment approaches for patients with mantle cell lymphoma who are transplant eligible or ineligible.

Dr Epstein-Peterson on the Treatment of Transplant-Eligible and -Ineligible Patients with MCL

Zachary Epstein-Peterson, MD, attending physician, Memorial Sloan Kettering Cancer Center, discusses important updates in mantle cell lymphoma (MCL) treatment, including the safety and feasibility of disease observation in patients with indolent MCL and the treatment of patients with 

Disease observation is safe in patients with indolent MCL who present with less aggressive or limited-stage disease, Epstein-Peterson says. Some patients can be observed for months or years after their initial MCL diagnosis without negative effects on their disease outcomes, Epstein-Peterson notes.

One category of patients in which observation is a safe strategy are those who have non-nodal leukemic MCL or MCL with minimal nodes that is predominantly in the spleen or circulating in the bloodstream, Epstein-Peterson explains. Another group of patients with MCL who can be safely observed are those with asymptomatic and indolent gastrointestinal (GI) tract disease that is found incidentally, such as through a routine colonoscopy, Epstein-Peterson says. The third group of patients in which MCL observation is safe, who are less common but still seen in the clinic, are those with predominantly nodal disease who may also have some GI tract disease and a low Ki67 proliferation index, but who do not have non-nodal leukemic disease and have a low disease burden, Epstein-Peterson emphasizes.

Further research has demonstrated the importance of considering patients' 

 mutation status when choosing frontline treatment strategies if observation is not appropriate, Epstein-Peterson says. The Nordic MCL2 (ISRCTN 87866680) and phase 2 Nordic MCL3 (NCT00514475) trials showed that patients with MCL with 

 aberrations who received intensive cytarabine-based chemoimmunotherapy followed by high-dose therapy and autologous stem cell rescue had shorter lengths of progression-free survival and overall survival than those without 

 mutations, Epstein-Peterson emphasizes. These findings indicate the importance of enrolling patients with 

-mutant MCL to clinical trials whenever possible, Epstein-Peterson concludes.

Zachary Epstein-Peterson, MD, discusses important updates in mantle cell lymphoma treatment, including the safety and feasibility of disease observation in patients with indolent MCL and the treatment of patients with TP53-mutated MCL.

Dr. Epstein-Peterson on Disease Observation and TP53 Mutations in MCL

Zachary Epstein-Peterson, MD, hematologist oncologist, Memorial Sloan Kettering Cancer Center, discusses pivotal clinical trials in the treatment of patients with mantle cell lymphoma (MCL).

Several clinical trials in MCL have shaped the way patients are treated, including the phase 3 SHINE trial (NCT01776840), Epstein-Peterson says. The trial evaluated the efficacy and safety of ibrutinib (Imbruvica) given in combination with bendamustine and rituximab (Rituxan) in patients who are 65 years of age or older with newly diagnosed MCL. Notably, the SHINE trial has informed new practices for transplant-ineligible patients, Epstein-Peterson adds.

In the transplant-eligible population, cytarabine is an important backbone of therapy, specifically for patients with newly diagnosed, 

 wild-type disease, Epstein-Peterson continues. The importance of rituximab maintenance post stem cell transplant has also been emphasized with recent trials and has become an important conversation in the context of the COVID-19 pandemic, Epstein-Peterson concludes.

Zachary Epstein-Peterson, MD, discusses pivotal clinical trials in the treatment of patients with mantle cell lymphoma.


Dr. Epstein-Peterson on Pivotal Clinical Trials in MCL

Zachary Epstein-Peterson, MD, hematologist and oncologist, Memorial Sloan Kettering Cancer Center, discusses the importance of treatment sequencing decisions in mantle cell lymphoma (MCL).

Many of the recent advancements made in treating MCL have been due to understanding the biology in patients and the heterogeneity of the disease, Epstein-Peterson says. Since MCL is not a single disease entity, it cannot be treated in the same fashion across all patients, Epstein-Peterson explains, adding that individualizing care for each patient is paramount for their outcomes.

For example, genetic testing in the up-front setting allows for a more tailored approach in patients with 

The plethora of tools available for the treatment of MCL allows clinicians to better understand how to best sequence and combine therapies, Epstein-Peterson continues. By understanding resistance mechanisms, clinicians can better target them and improve outcomes for patients with MCL, Epstein-Peterson concludes.

Zachary Epstein-Peterson, MD, discusses the importance of treatment sequencing decisions in mantle cell lymphoma.


Zachary Epstein-Peterson, MD

Articles

Dr Epstein-Peterson on the Use of CAR T-Cell Therapy in MCL

Dr Epstein-Peterson on the Treatment of Transplant-Eligible and -Ineligible Patients with MCL

Dr. Epstein-Peterson on Disease Observation and TP53 Mutations in MCL

Dr. Epstein-Peterson on Pivotal Clinical Trials in MCL

Dr. Epstein-Peterson on the Importance of Treatment Sequencing Decisions in MCL