MCL-1013

Concurrent High-Risk Features in Mantle Cell Lymphoma: Frequency and Impact

Carla Isabel Borre MD, MPH¹, Muhammad Azeem Khan MBBS¹, Aishwarya Pradeep MD¹, Ayo Samuel Falade MD, MBA¹, Laura Carola Magnano Mayer MD¹, Michelle Thorensen RN¹, Julia Wang^1,2, Enaya Epps², Adrienne Nedved PharmD, RPh, BCOP¹, Robin Klebig APRN, CNP, MSN¹, Gita Thanarajasingam MD¹, Urshila Durani MD, MPH¹, Arushi Khurana MBBS¹, JC Villasboas Bisneto MD¹, Jonas Paludo MD¹, Stephen Ansell MD, PhD¹, Thomas Habermann MD¹, Thomas Witzig MD¹, Yucai Wang MD, PhD¹, Jithma Abeykoon MD¹

¹Mayo Clinic, Rochester, MN, USA. ²Century High School, Rochester, MN, USA

Abstract

Context

MCL has a wide spectrum of outcomes influenced by clinical and biological features, some of which are included in the Mantle Cell Lymphoma International Prognostic Index combined (e.g., Ki-67); however, the prevalence and impact of high-risk features such as TP53 mutation and blastoid or pleomorphic morphology have not been well characterized. We describe the prevalence of concurrent high-risk features and their impact on outcomes. 

Design

Retrospective study 

Setting

Routine clinical practice 

Patients or Participants

Patients with MCL seen at Mayo Clinic (Rochester, MN), diagnosed between 2008 and 2026, with known TP53 mutation status (by clinical next-generation sequencing), morphology, and Ki-67. 

Main Outcome Measures

PFS and OS were analyzed by the Kaplan-Meier method.

Results

One hundred four patients were included, with a median age at diagnosis of 67 (range: 30–89) years. Most (76.9%) patients were male, 95.0% had stage 3 or 4 disease, 34.6% had TP53 mutation, 51.9% had Ki-67≥30%, and 14.4% had blastoid or pleomorphic morphology. Concurrent Ki-67≥30% and TP53 mutation were observed in 18.3% of patients, while 9.6% had both Ki-67≥30% and blastoid or pleomorphic morphology; 6.7% harbored both TP53 mutation and blastoid or pleomorphic morphology, and 3.8% harbored all three features. Median follow-up from diagnosis was 3.9 (95% CI: 3.2–5.7) years, and 73.5% of patients received frontline chemoimmunotherapy, while 26.2% received frontline BTKi-based therapy. Median PFS and OS differed significantly by the number of concurrent high-risk features present. Median PFS was 6.8 (95% CI: 4.0–NR) years, 5.3 (95% CI: 1.6–NR) years, 4.3 (95% CI: 2.1–NR) years, and 0.5 (95% CI: 0.08–NR) years for patients harboring zero, one, two, and three features, respectively (P<0.0001). Median OS similarly declined from 9.4 (95% CI: 3.66–NR) years in patients with one high-risk feature to 0.41 (95% CI: 0.08–NR) years in those harboring all three features. Similar PFS and OS rates were observed among patients treated with frontline chemoimmunotherapy and BTKi-based treatment when grouped by the number of high-risk features. 

Conclusion

The accumulation of high-risk features in MCL identifies a subgroup with inferior PFS, supporting comprehensive risk stratification incorporating TP53, morphology, and Ki-67.

BTKi: Bruton tyrosine kinase inhibitor, CI: confidence interval, Ki-67: antigen Kiel 67, MCL: mantle cell lymphoma, NR: not recorded, OS: overall survival, PFS: progression-free survival, TP53: tumor protein 53

Keywords

MCL, mantle cell lymphoma, TP53 mutation, Ki-67 proliferation index, blastoid morphology, pleomorphic morphology