Anita Kumar, MD, medical oncologist, Regional Care Network Medical Site Director, MSK Basking Ridge, Memorial Sloan Kettering Cancer Center, discusses considerations for the use of second-line BTK inhibitors in patients with mantle cell lymphoma (MCL) who progress on BTK inhibitors.

BTK inhibitors are standard second-line treatment for patients with relapsed/refractory MCL who progress after initial chemoimmunotherapy, Kumar says. There are 3 FDA-approved BTK inhibitors including ibrutinib (Imbruvica), acalabrutinib (Calquence), and zanubrutinib (Brukinsa), and some clinicians may favor the use of acalabrutinib or zanubrutinib due to the toxicity profiles of the 3 agents, Kumar adds.

Since patients with MCL are typically older and have multiple comorbidities, using acalabrutinib or zanubrutinib could reduce the risk of cardiovascular adverse effects, Kumar concludes. 

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Anita Kumar, MD, discusses considerations for the use of second-line BTK inhibitors in patients with mantle cell lymphoma who progress on BTK inhibitors.


Dr. Kumar on Treatment Considerations with BTK Inhibitors in MCL

Anita Kumar, MD, medical oncologist, Regional Care Network Medical Site Director, MSK Basking Ridge, Memorial Sloan Kettering Cancer Center, discusses treatment options for patients with mantle cell lymphoma (MCL) who progress on BTK inhibitors.

Finding suitable treatment options after a patient progresses or is intolerant of a covalent BTK inhibitor remains an unmet need in MCL, Kumar says. Since there are fewer therapeutic options available for those patients, outcomes are unfavorable, Kumar adds. The use of the noncovalent BTK inhibitor pirtobrutinib (LOXO-305) in patients had previously received a covalent BTK inhibitor achieved high response rates, which served as exciting data, Kumar explains.

In addition to its efficacy, pirtobrutinib showed to be a well-tolerated oral therapy with a favorable safety and limited treatment-related adverse effects leading to treatment discontinuation, Kumar continues. Noncovalent BTK inhibitors represent an easily accessible treatment option for patients who progress after traditional covalent BTK inhibitor therapies, Kumar concludes.

Anita Kumar, MD, discusses treatment options for patients with mantle cell lymphoma who progress on BTK inhibitors.


Dr. Kumar on Treatment Options for Patients Who Progress on a BTK Inhibitor in MCL

Anita Kumar, MD, medical oncologist, Regional Care Network Medical Site Director, MSK Basking Ridge, Memorial Sloan Kettering Cancer Center, discusses future directions with pirtobrutinib (LOXO-305) in mantle cell lymphoma (MCL). 

Pirtobrutinib is a BTK inhibitor that has shown activity in patients with MCL, including those who previously received standard BTK inhibitors, Kumar says. Moreover, pirtobrutinib appears to be well tolerated and could offer patients a convenient, once-daily dosing option, Kumar explains.

Additional studies evaluating pirtobrutinib are planned, such as a phase 3 study comparing pirtobrutinib with investigator’s choice of ibrutinib (Imbruvica), acalabrutinib (Calquence), or zanubrutinib (Brukinsa), Kumar continues. Further research is needed to inform whether pirtobrutinib can be combined with other agents, such as venetoclax (Venclexta) to enhance the efficacy observed with the BTK inhibitor alone, Kumar concludes.

Anita Kumar, MD, discusses future directions with pirtobrutinib in mantle cell lymphoma. 


Dr. Kumar on the Future Directions With Pirtobrutinib in MCL

Anita Kumar, MD, medical oncologist, Regional Care Network Medical Site Director, MSK Basking Ridge, Memorial Sloan Kettering Cancer Center, discusses efforts made to address areas of unmet need in mantle cell lymphoma.

Challenges still exist in treating patients with MCL who harbor 

 mutations, blastic disease, and primary refractory disease, and efforts are currently underway to identify which therapies may have activity in these subsets, according to Kumar. Recently, data with brexucabtagene autoleucel (formerly KTE-X19; Tecartus) suggest that the CAR T-cell therapy can improve efficacy, even in high-risk subsets, Kumar says. 

Because remissions are often shorter with standard chemotherapy/immunotherapy regimens, as well as novel targeted therapies, patients who experience early relapse, harbor 

 mutations, or have blastic disease should be referred to a specialized center with access to CAR T-cell therapy, Kumar concludes.

Anita Kumar, MD, discusses efforts made to address areas of unmet need in mantle cell lymphoma.

Dr. Kumar on Addressing Unmet Needs in Mantle Cell Lymphoma

Anita Kumar, MD, medical oncologist, Regional Care Network Medical Site Director, MSK Basking Ridge, Memorial Sloan Kettering Cancer Center, discusses navigating CAR T-cell therapy–related toxicities in mantle cell lymphoma (MCL).

In MCL, treatment with the CAR T-cell therapy brexucabtagene autoleucel (brexu-cel; Tecartus) is associated with a risk of adverse effects, including cytokine release syndrome (CRS) and neurotoxicity, Kumar says. Findings from the phase 2 ZUMA-2 trial (NCT02601313), which data led to the July 2020 FDA approval of brexu-cel, revealed that 15% and 31% of patients developed grade 3 or higher CRS and neurotoxicity, respectively. 

To mitigate the toxicity risk with brexu-cel, patients should be well selected, Kumar explains. Factors such as age, comorbidities, and disease status, including tumor burden and time of initial treatment, could be potential predictors for toxicity, Kumar says. As such, the field should work toward developing a greater understanding of how to select patients to optimize efficacy and quality of life, Kumar concludes. 

Anita Kumar, MD, discusses navigating CAR T-cell therapy–related toxicities in mantle cell lymphoma. 



Dr. Kumar on Navigating CAR T-Cell Therapy–Related Toxicities in MCL

Anita Kumar, MD, medical oncologist, Regional Care Network Medical Site Director, MSK Basking Ridge, Memorial Sloan Kettering Cancer Center, discusses the improved efficacy of venetoclax (Venclexta) when used in combination with ibrutinib (Imbruvica) compared with venetoclax or ibrutinib alone in mantle cell lymphoma (MCL). 

Venetoclax, when administered after BTK inhibitor failure, is associated with lower rates of efficacy, according to Kumar. Both BTK inhibitors and BCL-2 inhibitors have high overall response (OR) rates, but low complete response (CR) rates, providing an opportunity to improve the durability of response associated with venetoclax. 

The AIM study (NCT02471391) was an investigator-initiated, open-label, single-group, phase 2 trial. The study examined the combination of ibrutinib with venetoclax in patients with MCL to observe the potential synergy when BTK and BCL-2 inhibitors are combined, Kumar says. The results of this combination showed a high CR rate of 62%. Notably, the combination of venetoclax and ibrutinib together showed clinical activity in high-risk patients, such as patients with 

 mutations. In this subset, the overall and CR rate was approximately 50%, concludes Kumar. 

Anita Kumar, MD, discusses the improved efficacy of venetoclax when used in combination with ibrutinib compared with venetoclax or ibrutinib alone in mantle cell lymphoma. 

Dr. Kumar on the Clinical Implications of the AIM Study in Mantle Cell Lymphoma

Anita Kumar, MD, medical oncologist, Regional Care Network Medical Site Director, MSK Basking Ridge, Memorial Sloan Kettering Cancer Center, discusses patient factors to consider when selecting treatment in relapsed/refractory mantle cell lymphoma (MCL).

At the time of treatment initiation for patients with relapsed/refractory MCL, several patient considerations should be accounted for, including age, overall fitness, and existing comorbidities, Kumar explains. Patient goals with therapies should also be considered, Kumar adds. Some patients prefer to receive well-tolerated therapies to maximize quality of life, whereas others prefer to treat their MCL aggressively with all available options, Kumar says. Moreover, patient preference could determine whether they should be treated in a community setting vs an academic setting, Kumar adds. 

Other considerations include whether the patient is eligible for CAR T-cell therapy, autologous stem cell transplant, and allogeneic stem cell transplant, Kumar says. Regarding the latter, donor availability then becomes an additional factor to consider, Kumar concludes.

Anita Kumar, MD, discusses patient factors to consider when selecting treatment in relapsed/refractory mantle cell lymphoma.



Anita Kumar, MD

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