Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Observational Study
. 2024 Mar 12;8(5):1209-1219.
doi: 10.1182/bloodadvances.2023011152.

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

Ann Tivey  1   2 , Rohan Shotton  1   2 , Toby A Eyre  3 , David Lewis  4 , Louise Stanton  5 , Rebecca Allchin  6 , Harriet Walter  6 , Fiona Miall  6 , Rui Zhao  7 , Anna Santarsieri  8 , Rory McCulloch  9 , Mark Bishton  10 , Amy Beech  11 , Victoria Willimott  12 , Nicole Fowler  13 , Claudia Bedford  13 , Jack Goddard  14 , Sam Protheroe  15 , Angharad Everden  13 , David Tucker  13 , Josh Wright  14 , Vasavi Dukka  15 , Miriam Reeve  16 , Shankara Paneesha  17 , Mahesh Prahladan  18 , Andrew Hodson  18 , Iman Qureshi  19 , Manasvi Koppana  18 , Mary Owen  16 , Kushani Ediriwickrema  20 , Helen Marr  21 , Jamie Wilson  22 , Jonathan Lambert  20 , David Wrench  23 , Claire Burney  24 , Chloe Knott  24 , Georgina Talbot  25 , Adam Gibb  2 , Angela Lord  7 , Barry Jackson  7 , Simon Stern  26 , Taylor Sutton  27 , Amy Webb  28 , Marketa Wilson  28 , Nicky Thomas  28 , Jane Norman  29 , Elizabeth Davies  29 , Lisa Lowry  30 , Jamie Maddox  31 , Neil Phillips  25 , Nicola Crosbie  4 , Marcin Flont  32 , Emma Nga  33 , Andres Virchis  34 , Raisa Guerrero Camacho  35 , Wunna Swe  36 , Arvind Pillai  37 , Clare Rees  38 , James Bailey  39 , Steve Jones  40 , Susan Smith  40 , Faye Sharpley  2 , Catherine Hildyard  41 , Sajir Mohamedbhai  20 , Toby Nicholson  42 , Simon Moule  38 , Anshuman Chaturvedi  1   2 , Kim Linton  1   2
Affiliations
Observational Study

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

Ann Tivey et al. Blood Adv. .

Abstract

During the COVID-19 pandemic, ibrutinib with or without rituximab was approved in England for initial treatment of mantle cell lymphoma (MCL) instead of immunochemotherapy. Because limited data are available in this setting, we conducted an observational cohort study evaluating safety and efficacy. Adults receiving ibrutinib with or without 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%). A total of 149 patients from 43 participating centers were enrolled: 74.1% male, median age 75 years, 75.2% Eastern Cooperative Oncology Group status of 0 to 1, 36.2% high-risk, and 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%, and 33.8% required dose reductions/delays. At 15.6-month 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 = .05) and 78.7% (ibrutinib-rituximab) vs 64.9% (ibrutinib; P = .13). Median progression-free survival (PFS) was 26.0 months (all patients); 13.7 months (high risk) vs not reached (NR) (low risk; hazard ratio [HR], 2.19; P = .004). Median overall survival was NR (all); 14.8 months (high risk) vs NR (low risk; HR, 2.36; P = .005). Median post-ibrutinib survival was 1.4 months, longer in 41.9% patients receiving subsequent treatment (median, 8.6 vs 0.6 months; HR, 0.36; P = .002). Ibrutinib with or without 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.

PubMed Disclaimer

Conflict of interest statement

Conflict-of-interest declaration: T.A.E. reports education honorarium, advisory board honorarium, and travel support from Roche; honorarium, research support, and travel support to scientific conferences from Gilead; advisory board honorarium from Kite; honorarium from Janssen; honorarium and travel support to scientific conferences from AbbVie; honorarium and research funding from AstraZeneca; advisory board honorarium and trial steering committee fee from Loxo Oncology; advisory board honorarium and research funding from BeiGene; and advisory board honorarium from Incyte and Secura Bio. D.L. reports advisory board and sponsored meeting attendance fee from Janssen. R.M. reports honorarium from Janssen; and research funding from Sanofi. M.B. reports honorarium from Janssen. S.P. reports honorarium and/or travel support to scientific conferences from Gilead, Janssen, AbbVie, AstraZeneca, and Takeda; and advisory board honorarium from Incyte. The remaining authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Time to treatment discontinuation. Discontinuation due to toxicity is indicated by x.
Figure 2.
Figure 2.
Progression free and overall survival by risk group. (A) PFS and (B) OS.
Figure 3.
Figure 3.
Overall survival based on variables of interest. (A) ECOG PS, (B) sMIPI risk category, (C) rituximab use, (D) age, (E) LDH ratio, and (F) blastoid/pleomorphic morphology.
See this image and copyright information in PMC

References

    1. Maddocks K. Update on mantle cell lymphoma. Blood. 2018;132(16):1647–1656. - PubMed
    1. Wang ML, Blum KA, Martin P, et al. Long-term follow-up of MCL patients treated with single-agent ibrutinib: updated safety and efficacy results. Blood. 2015;126(6):739–745. - PMC - PubMed
    1. Wang ML, Rule S, Martin P, et al. Targeting BTK with ibrutinib in relapsed or refractory mantle-cell lymphoma. N Engl J Med. 2013;369(6):507–516. - PMC - PubMed
    1. Rule S, Dreyling M, Goy A, et al. Ibrutinib for the treatment of relapsed/refractory mantle cell lymphoma: extended 3.5-year follow up from a pooled analysis. Haematologica. 2019;104(5):e211–e214. - PMC - PubMed
    1. International Traditional Medicine Clinical Trial Registry ISRCTN11038174: ENRICH Ibrutinib for Untreated Mantle Cell Lymphoma. https://www.isrctn.com/ISRCTN11038174

Publication types