BACKGROUND: As oral targeted agents, such as ibrutinib, become more widely used, understanding the impact of suboptimal dosing on overall survival (OS) and progression-free survival (PFS) outside of clinical trials is imperative. PATIENTS AND METHODS: Data on ibrutinib discontinuation, dose reductions, and treatment interruptions were collected on 170 non-Hodgkin lymphoma and chronic lymphocytic leukemia (CLL; n = 115, 64%) patients treated with ibrutinib at a single institution. Ibrutinib dose adherence was calculated as the proportion of days in which ibrutinib was administered out of the total number of days ibrutinib was prescribed in the first 8 weeks. Kaplan-Meier curves and log-rank tests were used to compare conditional survival outcomes beyond 8 weeks in patients with ≥ 80% dose adherence and patients with < 80% dose adherence. RESULTS: Median OS among those who discontinued therapy for progression was poor (n = 51, 1.7 months; 95% confidence interval, 0.3-3.7). Lower dose adherence (< 80%) was associated with significantly worse PFS (P = .002) and OS (P = .021). However, among CLL patients, lower dose adherence was only associated with worse PFS (P = .043). Patients with early dose reductions had significantly worse PFS (P = .004) and OS (P = .014). Patients with dose interruptions lasting > 1 week had worse PFS (P = .047) but not OS (P = .577). CONCLUSION: In this observational study, non-Hodgkin lymphoma and CLL patients experienced poor outcomes after discontinuing ibrutinib for disease progression. The inferior survival related to suboptimal dose adherence of ibrutinib was predominantly due to early dose reduction. These data confirm poor survival in CLL and lymphoma patients alike after ibrutinib discontinuation, and support recommendations for full dose at treatment initiation.
BACKGROUND: As oral targeted agents, such as ibrutinib, become more widely used, understanding the impact of suboptimal dosing on overall survival (OS) and progression-free survival (PFS) outside of clinical trials is imperative. PATIENTS AND METHODS: Data on ibrutinib discontinuation, dose reductions, and treatment interruptions were collected on 170 non-Hodgkin lymphoma and chronic lymphocytic leukemia (CLL; n = 115, 64%) patients treated with ibrutinib at a single institution. Ibrutinib dose adherence was calculated as the proportion of days in which ibrutinib was administered out of the total number of days ibrutinib was prescribed in the first 8 weeks. Kaplan-Meier curves and log-rank tests were used to compare conditional survival outcomes beyond 8 weeks in patients with ≥ 80% dose adherence and patients with < 80% dose adherence. RESULTS: Median OS among those who discontinued therapy for progression was poor (n = 51, 1.7 months; 95% confidence interval, 0.3-3.7). Lower dose adherence (< 80%) was associated with significantly worse PFS (P = .002) and OS (P = .021). However, among CLLpatients, lower dose adherence was only associated with worse PFS (P = .043). Patients with early dose reductions had significantly worse PFS (P = .004) and OS (P = .014). Patients with dose interruptions lasting > 1 week had worse PFS (P = .047) but not OS (P = .577). CONCLUSION: In this observational study, non-Hodgkin lymphoma and CLLpatients experienced poor outcomes after discontinuing ibrutinib for disease progression. The inferior survival related to suboptimal dose adherence of ibrutinib was predominantly due to early dose reduction. These data confirm poor survival in CLL and lymphomapatients alike after ibrutinib discontinuation, and support recommendations for full dose at treatment initiation.
Authors: Anthony R Mato; Chadi Nabhan; Paul M Barr; Chaitra S Ujjani; Brian T Hill; Nicole Lamanna; Alan P Skarbnik; Christina Howlett; Jeffrey J Pu; Alison R Sehgal; Lauren E Strelec; Alexandra Vandegrift; Danielle M Fitzpatrick; Clive S Zent; Tatyana Feldman; Andre Goy; David F Claxton; Spencer Henick Bachow; Gurbakhash Kaur; Jakub Svoboda; Sunita Dwivedy Nasta; David Porter; Daniel J Landsburg; Stephen J Schuster; Bruce D Cheson; Pavel Kiselev; Andrew M Evens Journal: Blood Date: 2016-09-06 Impact factor: 22.113
Authors: Michael Hallek; Bruce D Cheson; Daniel Catovsky; Federico Caligaris-Cappio; Guillermo Dighiero; Hartmut Döhner; Peter Hillmen; Michael Keating; Emili Montserrat; Nicholas Chiorazzi; Stephan Stilgenbauer; Kanti R Rai; John C Byrd; Barbara Eichhorst; Susan O'Brien; Tadeusz Robak; John F Seymour; Thomas J Kipps Journal: Blood Date: 2018-03-14 Impact factor: 22.113
Authors: Eleonora Marostica; Juthamas Sukbuntherng; David Loury; Jan de Jong; Xavier Woot de Trixhe; An Vermeulen; Giuseppe De Nicolao; Susan O'Brien; John C Byrd; Ranjana Advani; Jesse McGreivy; Italo Poggesi Journal: Cancer Chemother Pharmacol Date: 2014-11-08 Impact factor: 3.333
Authors: Paul M Barr; Jennifer R Brown; Peter Hillmen; Susan O'Brien; Jacqueline C Barrientos; Nishitha M Reddy; Steven Coutre; Stephen P Mulligan; Ulrich Jaeger; Richard R Furman; Florence Cymbalista; Marco Montillo; Claire Dearden; Tadeusz Robak; Carol Moreno; John M Pagel; Jan A Burger; Samuel Suzuki; Juthamas Sukbuntherng; George Cole; Danelle F James; John C Byrd Journal: Blood Date: 2017-04-03 Impact factor: 22.113
Authors: Preetesh Jain; Philip A Thompson; Michael Keating; Zeev Estrov; Alessandra Ferrajoli; Nitin Jain; Hagop Kantarjian; Jan A Burger; Susan O'Brien; William G Wierda Journal: Cancer Date: 2017-02-07 Impact factor: 6.860
Authors: Ranjana H Advani; Joseph J Buggy; Jeff P Sharman; Sonali M Smith; Thomas E Boyd; Barbara Grant; Kathryn S Kolibaba; Richard R Furman; Sara Rodriguez; Betty Y Chang; Juthamas Sukbuntherng; Raquel Izumi; Ahmed Hamdy; Eric Hedrick; Nathan H Fowler Journal: J Clin Oncol Date: 2012-10-08 Impact factor: 44.544
Authors: Jeffrey A Jones; Peter Hillmen; Steven Coutre; Constantine Tam; Richard R Furman; Paul M Barr; Stephen J Schuster; Thomas J Kipps; Ian W Flinn; Ulrich Jaeger; Jan A Burger; Mei Cheng; Joi Ninomoto; Danelle F James; John C Byrd; Susan M O'Brien Journal: Br J Haematol Date: 2017-04-10 Impact factor: 6.998
Authors: Marine Solano; Etienne Daguindau; Cyril Faure; Pierre Loriod; Coline Pain; Anne-Cécile Maes; Pauline Marguet; Marie Kroemer; Anne Rumpler; Jean Fontan; Eric Deconinck; Samuel Limat; Anne-Laure Clairet Journal: Ann Hematol Date: 2021-05-03 Impact factor: 3.673
Authors: Anthony R Mato; Jeff P Sharman; Juliana M L Biondo; Mei Wu; Yong Mun; Su Y Kim; Kathryn Humphrey; Michelle Boyer; Qian Zhu; John F Seymour Journal: Haematologica Date: 2022-01-01 Impact factor: 9.941