Integrative analysis of clinicopathological features defines novel prognostic models for mantle cell lymphoma in the immunochemotherapy era: a report from The North American Mantle Cell Lymphoma Consortium
Authors: Vose Julie M. , Fu Kai , Wang Lu , Mansoor Adnan , Stewart Douglas , Cheng Hongxia , Smith Lynette , Yuan Ji , Qureishi Hina Naushad , Link Brian K. , Cessna Melissa H. , Barr Paul M. , Kahl Brad S. , Mckinney Matthew S. , Khan Nadia , Advani Ranjana H. , Martin Peter , Goy Andre H. , Phillips Tycel J. , Mehta Amitkumar , Kamdar Manali , Crump Michael , Pro Barbara , Flowers Christopher R. , Jacobson Caron A. , Smith Sonali M. , Stephens Deborah M. , Bachanova Veronika , Jin Zhaohui , Wu Shishou , Hernandez-Ilizaliturri Francisco , Torka Pallawi , Anampa-Guzmán Andrea , Kashef Farshid , Li Xing , Sharma Sunandini , Greiner Timothy C. , Armitage James O. , Lunning Matthew , Weisenburger Dennis D. , Bociek Robert G. , Iqbal Javeed , Yu Guohua , Bi Chengfeng ,   the North American Mantle Cell Lymphoma Consortium
Published: December 2023

Abstract
Background
Patients with mantle cell lymphoma (MCL) exhibit a wide variation in clinical presentation and outcome. However, the commonly used prognostic models are outdated and inadequate to address the needs of the current multidisciplinary management of this disease. This study aims to investigate the clinical and pathological features of MCL in the immunochemotherapy era and improve the prognostic models for a more accurate prediction of patient outcomes.

Methods
The North American Mantle Cell Lymphoma Project is a multi-institutional collaboration of 23 institutions across North America to evaluate and refine prognosticators for front-line therapy. A total of 586 MCL cases diagnosed between 2000 and 2012 are included in this study. A comprehensive retrospective analysis was performed on the clinicopathological features, treatment approaches, and outcomes of these cases. The establishment of novel prognostic models was based on in-depth examination of baseline parameters, and subsequent validation in an independent cohort of MCL cases.

Results
In front-line strategies, the use of hematopoietic stem cell transplantation was the most significant parameter affecting outcomes, for both overall survival (OS, p < 0.0001) and progression-free survival (PFS, p < 0.0001). P53 positive expression was the most significant pathological parameter correlating with inferior outcomes (p < 0.0001 for OS and p = 0.0021 for PFS). Based on the baseline risk factor profile, we developed a set of prognostic models incorporating clinical, laboratory, and pathological parameters that are specifically tailored for various applications. These models, when tested in the validation cohort, exhibited strong predictive power for survival and showed a stratification resembling the training cohort.

Conclusions
The outcome of patients with MCL has markedly improved over the past two decades, and further enhancement is anticipated with the evolution of clinical management. The innovative prognostic models developed in this study would serve as a valuable tool to guide the selection of more suitable treatment strategies for patients with MCL.