Ibrutinib as first line therapy for mantle cell lymphoma: A multicentre, real-world UK study

Ann Tivey, Rohan Shotton, Toby A Eyre, David Lewis, Louise Stanton, Rebecca Allchin, Harriet Sarah Walter, Fiona Miall, Rui Zhao, Anna Santarsieri, Rory McCulloch, Mark Bishton, Amy Beech, Victoria Clare Willimott, Nicole Fowler, Claudia Bedford, Jack Goddard, Samuel Protheroe, Angharad Everden, David L TuckerJoshua Wright, Srivasavi Dukka, Miriam Thomson, Shankara Paneesha, Mahesh Prahladan, Andrew Hodson, Iman Qureshi, Manasvi Koppana, Mary Owen, Kushani Ediriwickrema, Helen Marr, Jamie Wilson, Jonathan Lambert, David J Wrench, Claire N Burney, Chloe Knott, Georgina Talbot, Adam Gibb, Angela Lord, Barry Jackson, Simon Stern, Taylor Sutton, Amy Caitlin Webb, Marketa Wilson, Nicky Thomas, Jane Norman, Elizabeth Davies, Lisa Lowry, Jamie Maddox, Neil Phillips, Nicola Crosbie, Marcin Flont, Emma Lm Nga, Andres Virchis, Raisa Guerrero Camacho, Wunna Swe, Arvind Radhakrishna Pillai, Clare Rees, James Bailey, Steve Gareth Jones, Susan Smith, Faye Sharpley, Catherine Hildyard, Sajir Mohamedbhai, Toby Nicholson, Simon Moule, Anshuman Chaturvedi, Kim Linton

Research output: Contribution to journalArticlepeer-review


During the Covid-19 pandemic, ibrutinib +/- rituximab was approved in England for initial treatment of mantle cell lymphoma (MCL) instead of immunochemotherapy. As limited data are available in this setting, we conducted an observational cohort study evaluating safety and efficacy. Adults receiving ibrutinib +/- rituximab for untreated MCL were evaluated for treatment toxicity, response and survival, including outcomes in high-risk MCL (TP53 mutation/deletion/p53 overexpression, blastoid/pleomorphic, or Ki67 >/=30%). 149 patients from 43 participating centres were enrolled: 74.1% male, median age 75, 75.2% ECOG 0-1, 36.2% high-risk, 8.9% autologous transplant candidates. All patients received >/= 1 cycle ibrutinib (median 8 cycles), 39.0% with rituximab. Grade >/= 3 toxicity occurred in 20.3%, 33.8% required dose reductions/delays. At 15.6 months (mo) median follow-up, 41.6% discontinued ibrutinib; 8.1% due to toxicity. Of 104 response-assessed patients, overall (ORR) and complete response (CR) rates were 71.2% and 20.2% respectively. ORR was 77.3% (low-risk) vs. 59.0% (high-risk), p=0.05, and 78.7% (ibrutinib-rituximab) vs. 64.9% (ibrutinib), p=0.13. Median progression-free survival was 26.0mo (all patients); 13.7mo (high-risk) vs. not reached (NR) (low-risk), p=0.004. Median overall survival was NR (all); 14.8mo (high-risk) vs. NR (low-risk), p=0.005. Median post-ibrutinib survival was 1.4mo, longer in 41.9% patients receiving subsequent treatment (median 8.6 vs 0.6mo, p=0.002). Ibrutinib +/- rituximab was effective and well tolerated as first-line treatment of MCL, including older and transplant-ineligible patients. PFS and OS were significantly inferior in one-third of patients with high-risk disease and those unsuitable for post-ibrutinib treatment, highlighting the need for novel approaches in these groups.

Original languageEnglish
JournalBlood Advances
Publication statusE-pub ahead of print - 21 Dec 2023


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