Dr Visco on Ongoing Research to Optimize Upfront MCL Therapy

“Now we have the possibility to use many different compounds, which are becoming more and more powerful.”

Carlo Visco, MD, an associate professor of hematology in the Department of Medicine, coordinator of the Lymphoma Team in the Hematology and Bone Marrow Transplant Unit in the Section of Biomedical Innovation in the Department of Engineering for Innovative Medicine at the University of Verona, discussed ongoing trials for patients with mantle cell lymphoma (MCL) and the emerging challenge of optimally sequencing powerful compounds for the management of this disease.

Visco detailed 2 trials currently underway by the European MCL Network that are investigating novel upfront treatment approaches for patients with MCL. He highlighted the randomized phase 2 MCL Elderly III trial (20225018089600), which is enrolling an elderly patient population similar to those included in the phase 2 FIL_V-RBAC trial (NCT03567876). One arm is evaluating a chemotherapy-free combination regimen consisting of rituximab (Rituxan), ibrutinib (Imbruvica), and venetoclax (Venclexta). This arm is being compared with bendamustine plus rituximab and ibrutinib. Patients in both arms will receive maintenance therapy. The MCL Elderly III trial may provide crucial information regarding how elderly patients manage and respond to upfront chemotherapy-free regimens, especially those receiving a triplet combination.

Visco also emphasized the potential importance of data from the phase 2 CARMAN trial (NCT06482684). This trial is enrolling younger patients with MCL who present with high-risk features upfront. The study is comparing 2 intensive approaches: CAR T-cell therapy with brexucabtagene autoleucel (brexu-cel; Tecartus) administered after an initial short course of ibrutinib and rituximab vs the standard of care that was established by results from the phase 3 TRIANGLE study (NCT02858258 ), which investigated the addition of first-line ibrutinib induction and maintenance therapy to autologous stem cell transplant in patients with MCL.

Regarding the broader therapeutic environments of MCL and large B-cell lymphoma in general, the availability of numerous different compounds is accelerating therapeutic potency, Visco said. These powerful agents now include bispecific antibodies, CAR T-cell therapies, and various combination regimens. The central objective and substantial challenge facing hematologists is defining the correct sequencing strategy for this growing armamentarium of therapeutic options, according to Visco.

In MCL specifically, this sequencing problem is already pressing, as hematologists are currently striving to shift the most effective therapies to earlier lines of treatment, Visco reported. He emphasized the necessity of understanding subsequent treatment lines, noting that although second and third-line protocols have been established, they are rapidly subject to change in the future, he concluded.