Dr Jerkeman on the Importance of Recognizing the Biological Heterogeneity Within MCL

“The prognosis of patients with MCL is very dependent on the biology of the tumor and the genetics of the tumor.”

Mats Jerkeman, MD, a professor in the Department of Oncology at Lund University, underscored the importance of recognizing the biological heterogeneity within mantle cell lymphoma (MCL) and the unmet need for effective therapeutic strategies in patients with high-risk disease.
Jerkeman explained that prognosis in MCL is closely tied to the underlying genetics and histology of the tumor, with certain subgroups facing markedly inferior outcomes despite advances in therapy. Patients whose tumors harbor TP53 mutations, display blastoid histology, or demonstrate high proliferative activity are particularly vulnerable to relapse, Jerkeman noted. Although current treatment strategies, including chemoimmunotherapy, BTK inhibitors, and cellular therapies, have improved outcomes for many patients, their efficacy in this biologically aggressive subset remains limited.

Jerkeman emphasized that no consensus standard of care has been established for patients with high-risk MCL, reflecting the difficulty of managing these subgroups with currently available therapies. Although some of thesepatients may achieve durable remissions with novel agents, the overall prognosis remains poor, particularly in the relapsed or refractory setting. He stressed that relying on treatment strategies extrapolated from lower-risk populations fails to adequately address the unique challenges presented by high-risk disease biology.

Looking ahead, Jerkeman highlighted the need to prioritize the high-risk MCL population in clinical trial design and translational research. He underscored the importance of molecular characterization and targeted trial development to better define therapeutic options for high-risk patients. Investigating novel targeted therapies, immunotherapy combinations, and rational sequencing strategies will be essential to overcoming the resistance mechanisms associated with adverse biology.

In his view, advancing care for high-risk MCL requires a shift toward biology-driven clinical research. By focusing on the molecular and genetic determinants of aggressive disease, investigators may develop treatment strategies tailored to these patients rather than continuing to apply regimens effective only in standard-risk settings.

Jerkeman concluded that although therapeutic progress has been made in MCL overall, patients with high-risk genetic and histologic features remain underserved.