Ibrutinib as first line therapy for mantle cell lymphoma: a multicentre, real-world UK study
Abstract
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.
Author
Tivey, Ann
Shotton, Rohan
Eyre, Toby A
Lewis, David
Stanton, Louise
Allchin, Rebecca
Walter, Harriet Sarah
Miall, Fiona
Zhao, Rui
Santarsieri, Anna
McCulloch, Rory
Bishton, Mark
Beech, Amy
Willimott, Victoria Clare
Fowler, Nicole
Bedford, Claudia
Goddard, Jack
Protheroe, Samuel
Everden, Angharad
Tucker, David L
Wright, Joshua
Dukka, Srivasavi
Thomson, Miriam
Paneesha, Shankara
Prahladan, Mahesh
Hodson, Andrew
Qureshi, Iman
Koppana, Manasvi
Owen, Mary
Ediriwickrema, Kushani
Marr, Helen
Wilson, Jamie
Lambert, Jonathan
Wrench, David J
Burney, Claire N
Knott, Chloe
Talbot, Georgina
Gibb, Adam
Lord, Angela
Jackson, Barry
Stern, Simon
Sutton, Taylor
Webb, Amy Caitlin
Wilson, Marketa
Thomas, Nicky
Norman, Jane
Davies, Elizabeth
Lowry, Lisa
Maddox, Jamie
Phillips, Neil
Crosbie, Nicola
Flont, Marcin
Nga, Emma Lm
Virchis, Andres
Guerrero Camacho, Raisa
Swe, Wunna
Pillai, Arvind Radhakrishna
Rees, Clare
Bailey, James
Jones, Steve Gareth
Smith, Susan
Sharpley, Faye
Hildyard, Catherine
Mohamedbhai, Sajir
Nicholson, Toby
Moule, Simon
Chaturvedi, Anshuman
Linton, Kim
Shotton, Rohan
Eyre, Toby A
Lewis, David
Stanton, Louise
Allchin, Rebecca
Walter, Harriet Sarah
Miall, Fiona
Zhao, Rui
Santarsieri, Anna
McCulloch, Rory
Bishton, Mark
Beech, Amy
Willimott, Victoria Clare
Fowler, Nicole
Bedford, Claudia
Goddard, Jack
Protheroe, Samuel
Everden, Angharad
Tucker, David L
Wright, Joshua
Dukka, Srivasavi
Thomson, Miriam
Paneesha, Shankara
Prahladan, Mahesh
Hodson, Andrew
Qureshi, Iman
Koppana, Manasvi
Owen, Mary
Ediriwickrema, Kushani
Marr, Helen
Wilson, Jamie
Lambert, Jonathan
Wrench, David J
Burney, Claire N
Knott, Chloe
Talbot, Georgina
Gibb, Adam
Lord, Angela
Jackson, Barry
Stern, Simon
Sutton, Taylor
Webb, Amy Caitlin
Wilson, Marketa
Thomas, Nicky
Norman, Jane
Davies, Elizabeth
Lowry, Lisa
Maddox, Jamie
Phillips, Neil
Crosbie, Nicola
Flont, Marcin
Nga, Emma Lm
Virchis, Andres
Guerrero Camacho, Raisa
Swe, Wunna
Pillai, Arvind Radhakrishna
Rees, Clare
Bailey, James
Jones, Steve Gareth
Smith, Susan
Sharpley, Faye
Hildyard, Catherine
Mohamedbhai, Sajir
Nicholson, Toby
Moule, Simon
Chaturvedi, Anshuman
Linton, Kim
Citations
Altmetric:
Date
2023-12-21
Type
Article
Subject
Haematology, Oncology. Pathology.
Collections
Citation
Tivey A, Shotton R, Eyre TA, Lewis D, Stanton L, Allchin R, Walter H, Miall F, Zhao R, Santarsieri A, McCulloch R, Bishton M, Beech A, Willimott V, Fowler N, Bedford C, Goddard J, Protheroe S, Everden A, Tucker D, Wright J, Dukka V, Reeve M, Paneesha S, Prahladan M, Hodson A, Qureshi I, Koppana M, Owen M, Ediriwickrema K, Marr H, Wilson J, Lambert J, Wrench D, Burney C, Knott C, Talbot G, Gibb A, Lord A, Jackson B, Stern S, Sutton T, Webb A, Wilson M, Thomas N, Norman J, Davies E, Lowry L, Maddox J, Phillips N, Crosbie N, Flont M, Nga E, Virchis A, Camacho RG, Swe W, Pillai A, Rees C, Bailey J, Jones S, Smith S, Sharpley F, Hildyard C, Mohamedbhai S, Nicholson T, Moule S, Chaturvedi A, Linton K. Ibrutinib as first-line therapy for mantle cell lymphoma: a multicenter, real-world UK study. Blood Adv. 2024 Mar 12;8(5):1209-1219. doi: 10.1182/bloodadvances.2023011152.
Journal / Source Title
Blood Advances
DOI
10.1182/bloodadvances.2023011152
PMID
38127279
Publisher
American Society of Hematology
Publisher’s URL
https://ashpublications.org/bloodadvances