Matthew S. McKinney, MD, cellular therapy specialist, hematologic oncologist, hematologist (malignant), Duke Cancer Center, Duke Health, discusses the potential for curative-intent therapies in mantle cell lymphoma (MCL).

The treatment of patients MCL has improved significantly in recentyears, McKinney says. However, there is still a long way to go in order to cure patients, McKinney explains. The field is optimistic that, in the future, patients with MCL will have improved treatment options compared with the current standards, McKinney adds.

Moreover, recent studies have shown that with modalities like CAR T-cell therapy could be curative for patients with MCL, McKinney concludes.

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Matthew S. McKinney, MD, discusses the potential for curative-intent therapies in mantle cell lymphoma. 

Dr. McKinney on the Potential for Curative-Intent Therapies in MCL 

Matthew S. McKinney, MD, cellular therapy specialist, hematologic oncologist, hematologist (malignant), Duke Health, discusses the emergence of CAR T-cell therapy in relapsed/refractory mantle cell lymphoma (MCL).

The FDA approval of brexucabtagene autoleucel (Tecartus) represented the first CD19-directed CAR T-cell therapy available for use in patients with relapsed/refractory MCL. The therapy appears more efficacious and has shown prolonged survival compared with other available therapies for this patient population, McKinney says. 

Despite the excitement surrounding CAR T-cell therapy, questions regarding optimal sequencing and patient selection remain unanswered, McKinney explains. Not all patients with MCL will be eligible for CAR T-cell therapy for reasons including frailty, caregiver status, or inadequate lymphocyte collection.


Clinical trials are evaluating whether CAR T-cell therapy should be sequenced in the second-line setting before or with BTK inhibitors, McKinney concludes.

Matthew S. McKinney, MD, discusses the emergence of CAR T-cell therapy in relapsed/refractory mantle cell lymphoma.



Dr. McKinney on the Emergence of CAR T-Cell Therapy in Relapsed/Refractory MCL 

Matthew S. McKinney, MD, cellular therapy specialist, hematologic oncologist, hematologist (malignant), Duke Health, discusses emerging therapeutic strategies in mantle cell lymphoma (MCL).

Similar to other B-cell lymphomas, novel agents, as well as strategies combining established agents are being investigated in MCL, McKinney explains. 

The results of the phase 3 SYMPATICO trial (NCT03112174) comparing ibrutinib (Imbruvica) plus venetoclax (Venclexta) or ibrutinib plus placebo in patients with MCL are highly anticipated, McKinney says. The findings will determine whether the combination of ibrutinib and venetoclax can deepen responses and lead to minimal residual disease–negative remissions in the second- and later-line settings for this patient population. 

Extrapolating from advances in other B-cell lymphomas, novel agents such as tafasitamab-cxix (Monjuvi), loncastuximab tesirine-lpyl (Zynlonta), and CD3- or CD20-directed bispecific T-cell engagers, could have utility alone or in combination regimens for patients with MCL. Moreover, these agents could provide treatment options for patients who are ineligible for CAR T-cell therapy or progress after BTK inhibitors or CAR T-cell therapy, McKinney concludes.

Matthew S. McKinney, MD, cellular therapy specialist, hematologic oncologist, hematologist (malignant), Duke Health, discusses emerging therapeutic strategies in mantle cell lymphoma (MCL).  



Dr. McKinney on Emerging Therapeutic Strategies in MCL 

Matthew S. McKinney, MD, cellular therapy specialist, hematologic oncologist, hematologist (malignant), Duke Health, discusses the expanding role of BTK inhibitors in mantle cell lymphoma (MCL).

Several different BTK inhibitors are available for the treatment of patients with relapsed/refractory MCL, including ibrutinib (Imbruvica), which exhibited higher response rates compare with other traditional agents. BTK inhibitors are used for patients who have had progression after aggressive up-front chemoimmunotherapy, or autologous stem cell transplant, McKinney explains. When comparing ibrutinib with regimens such as single-agent bortezomib (Velcade), bortezomib plus rituximab (Rituxan), or lenalidomide (Revlimid) plus rituximab, the BTK inhibitor demonstrated favorable overall and complete response rates compared with the other strategies, McKinney says.

More recently, FDA approvals for acalabrutinib (Calquence) and zanubrutinib (Brukinsa) have been granted for patients with relapsed/refractory MCL, McKinney continues. Overall, this is important because if there are adverse effects with ibrutinib, an alternative BTK inhibitor can be selected, McKinney concludes.

Matthew S. McKinney, MD, discusses the expanding role of BTK inhibitors in mantle cell lymphoma. 


Dr. McKinney on the Expanding Role of BTK Inhibitors in MCL

Matthew S. McKinney, MD, assistant professor of medicine, Duke University School of Medicine, co-director of the Molecular Tumor Board, Duke Cancer Institute, discusses ongoing work in mantle cell lymphoma (MCL).

A lot of ongoing research in MCL is being geared toward chemotherapy-free induction and relapsed/refractory therapy, McKinney says. The BTK inhibitors ibrutinib (Imbruvica) and acalabrutinib (Calquence) have been very important additions to the armamentarium, and building on that success with drugs like lenalidomide (Revlimid) and CD20 monoclonal antibodies is exciting for the field. Whether these agents can be moved into the frontline setting is another unanswered question.

Another area of debate is in which induction chemotherapy regimen works best. Ongoing studies are looking at this, says McKinney. Moreover, what is the role of consolidation stem cell transplant, specifically in patients with minimal residual disease negativity? Duke Cancer Institute is one of many institutions investigating that question.

Matthew S. McKinney, MD, assistant professor of medicine, Duke University School of Medicine, co-director of the Molecular Tumor Board, Duke Cancer Institute, discusses ongoing work in mantle cell lymphoma.

Dr. McKinney Discusses Ongoing Work in MCL

Matthew S. McKinney, MD, assistant professor of medicine, Duke University School of Medicine, co-director of the Molecular Tumor Board, Duke Cancer Institute, discusses the watch-and-wait approach in mantle cell lymphoma (MCL).

About 10% to 15% of patients with newly diagnosed MCL are appropriate for active surveillance, McKinney says. First, a physician should check for symptoms that indicate a need for immediate treatment. Identifying molecular markers in a patient is also crucial, as 

 mutations and blastoid variant histology represent an aggressive biology.

Beyond that, McKinney adds, physicians should rely on clinical judgement based on pathologic markers like SOX11. Data show that patients do well with the watch-and-wait approach if they have indolent disease. Effectively utilizing this strategy can save the patient months or even years from potentially toxic treatment, says McKinney.

Matthew S. McKinney, MD, assistant professor of medicine, Duke University School of Medicine, co-director of the Molecular Tumor Board, Duke Cancer Institute, discusses the watch-and-wait approach in mantle cell lymphoma.

Matthew S. McKinney, MD

Articles

Dr. McKinney on the Potential for Curative-Intent Therapies in MCL

Dr. McKinney on the Emergence of CAR T-Cell Therapy in Relapsed/Refractory MCL

Dr. McKinney on Emerging Therapeutic Strategies in MCL

Dr. McKinney on the Expanding Role of BTK Inhibitors in MCL

Dr. McKinney Discusses Ongoing Work in MCL

Dr. McKinney Discusses the Watch-and-Wait Approach in MCL