Australian experience with ibrutinib in patients with relapsed/refractory mantle cell lymphoma: a study from the Lymphoma and Related Diseases Registry

Abstract

Bruton’s tyrosine kinase inhibitors (BTKi) have an established role in the management of patients with relapsed/refractory mantle cell lymphoma (MCL). However, scant data exist on outcomes of patients ineligible for clinical trials testing these therapies. We describe a contemporary cohort of relapsed/refractory MCL patients from the Australasian Lymphoma and Related Diseases Registry treated with ibrutinib December 2014 until July 2018, to determine the proportion potentially eligible for original trials, reasons for ineligibility and survival outcomes. Of 44 patients, 41% met one or more exclusion criteria from previous phase II/III MCL BTKi studies. Median progression-free and overall survival were 13.7 months (95% CI 6.2–28.1) and 15.6 months (95% CI 10.8–29.6) respectively and were shorter in patients excluded from clinical trials based on ECOG ≥2. Ibrutinib has demonstrable clinical effectiveness in a population enriched for unfit and trial-ineligible patients, and a need for more inclusive enrollment criteria in future BTKi studies is highlighted.

Keywords:

• Mantle cell lymphoma
• ibrutinib
• Australasian Lymphoma and Related Diseases Registry

Acknowledgements

We acknowledge the additional contributing project team, A/Prof Zoe McQuilten, Gayathri St George, Monash University and all LaRDR participants, site staff and additional site Principal Investigators as follows: Dr John Balendra, Royal Perth Hospital, Australia; Dr Allison Barraclough, Fiona Stanley Hospital, Australia; Dr Leanne Berkahn, Auckland City Hospital, New Zealand; Dr Annmarie Bosco, Prince of Wales Hospital, Australia; Dr Duncan Carradice, Western Health, Australia; Dr Hun Chuah, Rockingham General Hospital, Australia; Dr Luke Coyle, Royal North Shore Hospital, Australia; Dr Kyle Crassini, Coffs Harbour Health Campus, Australia; A/Prof Melita Kenealy, Cabrini Health, Australia; A/Prof Matthew Ku, St Vincent’s Hospital Melbourne, Australia; Dr Teresa Leung, Northern Health, Australia; Dr Kate Manos, Flinders Medical Centre, Australia; Dr Susan Morgan, The Alfred, Australia; Dr Howard Mutsando, Toowoomba Hospital, Australia; Dr Manjunath Narayana, Sunshine Coast University Hospital, Australia; Dr Emma Palfreyman, Royal Darwin Hospital, Australia; Prof Miles Prince, Epworth, Victoria, Australia; Dr Sumita Ratnasingam, University Hospital Geelong, Australia; Dr Jock Simpson, Port Macquarie Base Hospital, Australia; Prof Judith Trotman, Concord Hospital, Australia; Dr Nicholas Viiala, Liverpool Hospital, Australia; Dr Joel Wight, Townsville Hospital, Australia.

Disclosure statement

Armytage T has research funding and honoraria from Novartis, and research funding from Roche. Minson A has research funding from Novartis and Roche. Chong G reports a consulting role with Bristol Myers Squibb, and research funding from Pharmacyclics, Bristol Myers Squibb, Merck Serono, Bayer, Morphosys, Incyte, Regeneron, Hutch-Med, AstraZeneca, and Roche. Johnson A reports a consulting or advisory role with Roche, Beigene, Novartis, and Sanofi. Hawkes EA has received advisory board honoraria from Bristol Myers Squibb, and institutional advisory fees from Roche, Gilead, Antengene, Link, Novartis, Beigene, and Merck Sharpe & Dohme, speakers fees from Regeneron, Janssen, AstraZeneca (paid to institution), Roche (paid to institution) and research funding paid to her institution from Roche, Bristol-Myers Squibb, Merck KGaA, and AstraZeneca. The Lymphoma and Related Diseases Registry has received funding from Abbvie, Antengene, AstraZeneca, Beigene, Bristol Myers Squibb, Celgene, Gilead, Janssen, Novartis, Roche, Sandoz, and Takeda. The remaining authors have no COI declared.

Additional information

Funding

This work is supported by Janssen Pharmaceuticals.