Mantle cell lymphoma outcomes following sequential first-line bendamustine-rituximab and second-line Bruton’s tyrosine kinase inhibitor therapy

Addition of Bruton's tyrosine kinase inhibitor (BTKi) to first-line (1 L) bendamustine-rituximab (BR) improved progression-free survival (PFS) in patients with mantle cell lymphoma (MCL) in the SHINE and ECHO trials. We investigated whether sequential treatment with 1 L BR and second-line (2 L) BTKi can result in similar cumulative PFS compared to BR-BTKi combination therapy, using a multicenter cohort of 755 patients treated with 1 L BR between 2014 and 2020. Event-free survival (EFS), EFS2, and overall survival (OS) were analyzed. By intention-to-treat (ITT), EFS2 was defined as time from 1 L BR start to progression/relapse or retreatment following 2 L BTKi or death. After a median follow-up of 61.4 (95% CI 56.4-65.9) months, the median EFS after 1 L BR was 34.2 (95% CI 31.5-38.4) months. The median EFS2 following 1 L BR and 2 L BTKi by ITT analysis was 64.8 (95% CI 56.7-82.8) months, and the 5-year OS rate after 1 L BR was 57.9% (95% CI 54.1-62.0%), close to SHINE and ECHO results. Patients without high-risk features (high simplified MIPI, high Ki-67, blastoid/pleomorphic morphology, TP53 mutation, or complex karyotype) had more favorable survival outcomes. These results suggest that sequential treatment with 1 L BR and 2 L BTKi remains reasonable for select patients with MCL, particularly those without high-risk features.

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Publication Details

Journal
Blood Cancer Journal
Published
2026-04-25
DOI
https://doi.org/10.1038/s41408-026-01507-w
Primary Topic
Lymphoma Diagnosis and Treatment
Type
article
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article

Mantle cell lymphoma outcomes following sequential first-line bendamustine-rituximab and second-line Bruton’s tyrosine kinase inhibitor therapy

Reem Karmali, Ashlee Joseph, David A. Bond, Stefan Klaus Barta et al.
Blood Cancer Journal
Lymphoma Diagnosis and Treatment
article

Mantle cell lymphoma outcomes following sequential first-line bendamustine-rituximab and second-line Bruton’s tyrosine kinase inhibitor therapy

Reem Karmali, Ashlee Joseph, David A. Bond, Stefan Klaus Barta, Philip R. Young, Craig Anthony Portell, Muhamad Alhaj Moustafa, Drew G. Gerber, Izidore S. Lossos, I. Brian Greenwell, Georgios Pongas, Rahul S. Bhansali, Zoey I. Harris, Imran Nizamuddin, Marcus R. Messmer, Eric Mou, Tamara Kay Moyo, Steven R. Hwang, Laveniya Kugathasan, Reid W. Merryman, Alexey Valeryevich Danilov, Brad S. Kahl, Christine E. Ryan, Nilanjan Ghosh, Natalie Sophia Grover, James R. Cerhan, Manali K. Kamdar, Arash Velayati, Preetesh Jain, Anita Kumar, Javier Muñoz, Michael L. Wang, Yucai Wang, Melissa C. Larson, Nazneen B. Khan, Jacob Anna, Diego Villa, Christine Argao, Aung M. Tun, Alexander V. Stanisic, Evguenia Ouchveridze, Anthony C. Stack, Peter Martin, Sabarish R. Ayyappan, Patrick M. Reagan, Matthew J. Maurer, Amitkumar Mehta, Kami J. Maddocks, Brian T. Hill, Taylor R. Brooks, Firas Baidoun, Mayur S. Narkhede, Priyanka A. Pophali, Jia Ruan, Jonathon B. Cohen, Lauren G. Banaszak
article en

Abstract

Addition of Bruton's tyrosine kinase inhibitor (BTKi) to first-line (1 L) bendamustine-rituximab (BR) improved progression-free survival (PFS) in patients with mantle cell lymphoma (MCL) in the SHINE and ECHO trials. We investigated whether sequential treatment with 1 L BR and second-line (2 L) BTKi can result in similar cumulative PFS compared to BR-BTKi combination therapy, using a multicenter cohort of 755 patients treated with 1 L BR between 2014 and 2020. Event-free survival (EFS), EFS2, and overall survival (OS) were analyzed. By intention-to-treat (ITT), EFS2 was defined as time from 1 L BR start to progression/relapse or retreatment following 2 L BTKi or death. After a median follow-up of 61.4 (95% CI 56.4-65.9) months, the median EFS after 1 L BR was 34.2 (95% CI 31.5-38.4) months. The median EFS2 following 1 L BR and 2 L BTKi by ITT analysis was 64.8 (95% CI 56.7-82.8) months, and the 5-year OS rate after 1 L BR was 57.9% (95% CI 54.1-62.0%), close to SHINE and ECHO results. Patients without high-risk features (high simplified MIPI, high Ki-67, blastoid/pleomorphic morphology, TP53 mutation, or complex karyotype) had more favorable survival outcomes. These results suggest that sequential treatment with 1 L BR and 2 L BTKi remains reasonable for select patients with MCL, particularly those without high-risk features.

Blood Cancer Journal
Northwestern University (US), University of North Carolina at Chapel Hill (US), University of Iowa (US), Fox Chase Cancer Center (US), Cleveland Clinic (US), Memorial Sloan Kettering Cancer Center (US), The University of Texas MD Anderson Cancer Center (US), University of Wisconsin–Madison (US), University of British Columbia (CA), University of Miami (US), Emory University (US), Medical University of South Carolina (US), Washington University in St. Louis (US), Cornell University (US), Spinal Cord Injury BC (CA), WinnMed (US), University of Alabama at Birmingham (US), Levine Cancer Institute (US), City of Hope (US), Dana-Farber Cancer Institute (US), Mayo Clinic in Arizona (US), Mayo Clinic Hospital (US), University of Kansas Medical Center (US), Mayo Clinic in Florida (US), Weill Cornell Medicine (US), Winship Cancer Institute, University of Virginia (US), University of Colorado Anschutz Medical Campus (US), The Ohio State University (US), University of Rochester (US), University of Pennsylvania (US), University of Colorado Denver (US)
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