Unraveling Resistance and Heterogeneity in Mantle Cell Lymphoma Management

Although strides have been made with Bruton tyrosine kinase (BTK) inhibitors and CAR-T cell therapy, relapse and resistance remain significant hurdles in treating patients with mantle cell lymphoma (MCL). The Lymphoma Research Foundation's 2023 MCL Scientific Consortium and Workshop addressed these complexities, aiming to dissect the intricate biology of MCL and propel progress towards a cure.

CancerNetwork® spoke with leaders in the MCL field to better understand the aim of the consortium and the advancements they hope to see in the space. The journal ONCOLOGY® published these findings in the February 2024 issue. The interviews included Elias Campo, MD, PhD, research director and professor of anatomic pathology at the Hospital Clinic of the University of Barcelona; Michael Wang, MD, professor in the Department of Lymphoma and Myeloma at The University of Texas, MD Anderson Cancer Center; Martin Dreyling, MD, PhD, professor of Medicine in the Department of Medicine and head of the Medical Clinic 3 at the University of Munich-Grosshadern in Germany; and Julie M. Vose, MD, MBA, Neumann M. and Mildred E. Harris Professor and division chief in the Division of Hematology at the University of Nebraska Medical Center and coeditor in chief of ONCOLOGY. 

The consortium touched on t(11;14), which dysregulates cyclin D1 and fuels uncontrolled cell growth. Additionally, research presented at the consortium revealed other molecular pathways contributing to treatment resistance and relapse, highlighting the heterogeneous nature of the disease. This heterogeneity underscored the need for personalized treatment strategies and biomarker-based prognostics, a notion further emphasized by multiple findings on the predictive value of specific gene mutations.

Beyond understanding the inner workings of MCL, presentations also focused on novel therapeutic avenues. Specifically, there were encouraging data on the potential of next-generation BTK inhibitors including acalabrutinib (Calquence) to overcome resistance.

Challenges such as the limitations of current risk stratification models remain, underscoring the need for robust biomarkers to guide early interventions and optimize treatment selection. Additionally, the consortium featured a discussion on addressing a lack of diversity in clinical trial populations, which may help increase treatment access for those with various medical conditions.

“…The patient population that has a disease is not always [represented] in the clinical trials. That’s why it’s important to be able to have a diversity of patients in clinical trials: to test these new therapies because [patients] may have other medical conditions that would change the outcome of trials and not be necessarily representative of the entire patient population with that disease,” Vose said. “It’s important to try to advance the treatment of a very diverse patient population through these clinical trial mechanisms.”