Ibrutinib as first-line therapy for mantle cell lymphoma: a multicenter, real-world UK study
Authors: Tivey Ann , Shotton Rohan , Eyre Toby A. , Lewis David , Stanton Louise , Allchin Rebecca , Walter Harriet , Miall Fiona , Zhao Rui , Santarsieri Anna , McCulloch Rory , Bishton Mark , Beech Amy , Willimott Victoria , Fowler Nicole , Bedford Claudia , Goddard Jack , Protheroe Sam , Everden Angharad , Tucker David , Wright Josh , Dukka Vasavi , Reeve Miriam , Paneesha Shankara , Prahladan Mahesh , Hodson Andrew , Qureshi Iman , Koppana Manasvi , Owen Mary , Ediriwickrema Kushani , Marr Helen , Wilson Jamie , Lambert Jonathan , Wrench David , Burney Claire , Knott Chloe , Talbot Georgina , Gibb Adam , Lord Angela , Jackson Barry , Stern Simon , Sutton Taylor , Webb Amy , Wilson Marketa , Thomas Nicky , Norman Jane , Davies Elizabeth , Lowry Lisa , Maddox Jamie , Phillips Neil , Crosbie Nicola , Flont Marcin , Nga Emma , Virchis Andres , Camacho Raisa Guerrero , Swe Wunna , Pillai Arvind , Rees Clare , Bailey James , Jones Steve , Smith Susan , Sharpley Faye , Hildyard Catherine , Mohamedbhai Sajir , Nicholson Toby , Moule Simon , Chaturvedi Anshuman , Linton Kim 
Published: December 2023

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.