Dr Cohen on Treatment Considerations for Relapsed/Refractory MCL

Jonathon B. Cohen, MD, MS, associate professor, Department of Hematology and Medical Oncology, codirector, Lymphoma Program, university chair, Data and Safety Monitoring Committee, Winship Cancer Institute, Emory University School of Medicine, discusses treatment considerations for patients with relapsed/refractory mantle cell lymphoma (MCL), highlighting the role of pirtobrutinib (Jaypirca) in the early management of this disease.

results from the phase 1/2 BRUIN study (NCT03740529)

 of pirtobrutinib in previously treated patients with relapsed/refractory MCL were presented. Historically, patients previously treated with a covalent BTK inhibitor have faced dismal outcomes, Cohen begins. In the current MCL treatment paradigm, pirtobrutinib has emerged as a viable treatment option, and is FDA approved for patients who have progressed following covalent BTK inhibitor therapy or discontinued treatment due to intolerance, he explains.

Additionally, CD19-directed CAR T-cell therapy may be considered for patients with MCL. However, although brexucabtagene autoleucel (brexu-cel; Tecartus) yields a high overall response rate and sustained response for patients achieving a complete response, it is not suitable for all patients due to its intensity, Cohen emphasizes.

When managing relapsed MCL, especially in patients ineligible for covalent BTK inhibitor therapy, treatment decisions hinge on individual patient status and comorbidities, he expands. The prognosis for BTK inhibitor–pretreated patients with MCL has historically been bleak, he says, adding that the approval of pirtobrutinib provides a treatment option for this patient subgroup that is less intensive compared with CAR T-cell therapy. There is considerable interest in investigating whether pirtobrutinib could play a role in earlier MCL management, Cohen states.

Although pirtobrutinib has generated good tolerability and activity in patients with MCL previously treated with covalent BTK inhibitors, updates shared at the 2023 ASH Annual Meeting regarding pirtobrutinib's efficacy in BTK inhibitor–naive patients are also promising, he continues. The large phase 3 BRUIN-MCL-321 trial (NCT04662255) is underway to ascertain whether a noncovalent BTK inhibitor such as pirtobrutinib might be preferable over covalent BTK inhibitors for BTK inhibitor–naive patients, Cohen reports. This trial represents a significant advancement in evaluating pirtobrutinib and determining its optimal placement within the broader treatment armamentarium for MCL, he concludes.

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Jonathon B. Cohen, MD, MS, discusses treatment considerations for mantle cell lymphoma and the role of pirtobrutinib in the management of this disease.

Jonathon B. Cohen, MD, MS, associate professor, Department of Hematology and Medical Oncology, Emory University School of Medicine, co-director, Lymphoma Program, and medical director, Infusion Services, Winship Cancer Institute of Emory University, discusses the design of the phase III ELEVATE-TN trial in chronic lymphocytic leukemia (CLL).

The ELEVATE-TN trial was designed to evaluate the second-generation BTK inhibitor acalabrutinib (Calquence). The agent was designed to be more specific inhibitor of BTK and result in less off-target toxicity versus ibrutinib (Imbruvica), says Cohen. In the trial, acalabrutinib was combined with obinutuzumab (Gazvya) and compared with the combination of obinutuzumab and chlorambucil.

According to topline findings from the trial, the study met its primary endpoint of improved progression-free survival with the BTK-based combination in patients with treatment-naïve CLL. Although data from the trial have yet to be presented, Cohen believes they will reinforce the idea that BTK-based therapy is superior to chemotherapy in CLL.

Dr. Cohen on the ELEVATE-TN Trial in CLL

Jonathon B. Cohen, MD, MS, associate professor, Department of Hematology and Medical Oncology, Emory University School of Medicine, co-director, Lymphoma Program, and medical director, Infusion Services, Winship Cancer Institute of Emory University, discusses fixed-duration therapy in chronic lymphocytic leukemia (CLL).

Although ibrutinib (Imbruvica) is an active and well tolerated agent in CLL, it is given indefinitely, says Cohen. Although some patients do not mind taking a pill indefinitely, others would prefer a fixed-duration therapy to offset some of the financial and treatment-related toxicities of the BTK inhibitor. 

As such, there is a lot of interest in evaluating time-limited therapy with combination therapies whereby patients who achieve a deep response could potentially discontinue therapy, concludes Cohen.

Jonathon B. Cohen, MD, MS, discusses fixed-duration therapy in chronic lymphocytic leukemia.

Dr. Cohen on Fixed-Duration Therapy in CLL

Jonathon B. Cohen, MD, MS, associate professor, Department of Hematology and Medical Oncology, Emory University School of Medicine, co-director, Lymphoma Program, medical director, Infusion Services, Winship Cancer Institute of Emory University, discusses the role of chemoimmunotherapy in chronic lymphocytic leukemia (CLL).

Historically, chemoimmunotherapy was the standard of care in the frontline and relapsed/refractory settings in CLL. Standard fludarabine, cyclophosphamide, and rituximab (Rituxan; FCR) has shown prolonged disease remission without need for additional therapy,explains Cohen.

However, oral agents have provided an alternative that could spare patients the short- and long-term toxicities associated with chemoimmunotherapy, says Cohen. Although oral agents are recommended for most patients, chemoimmunotherapy may be a preferred regimen in young patients with low-risk CLL, Cohen concludes.

Jonathon B. Cohen, MD, MS, discusses the role of chemoimmunotherapy in chronic lymphocytic leukemia. 
 

Jonathon B. Cohen, MD, MS

Articles

Dr Cohen on Treatment Considerations for Relapsed/Refractory MCL

Dr. Cohen on the ELEVATE-TN Trial in CLL

Dr. Cohen on Fixed-Duration Therapy in CLL

Dr. Cohen on the Use of Chemoimmunotherapy in CLL