Real-World Comparison of First-Line Treatment Adherence Between Single-Agent Ibrutinib and Acalabrutinib in Patients with Chronic Lymphocytic Leukemia

Purpose Increased dosing frequency adversely affects treatment adherence and outcomes in chronic diseases; however, such data related to treatment adherence is lacking in chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). This study compared adherence between patients treated with ibrutinib (once-daily) versus acalabrutinib (twice-daily) as first-line (1L) therapy for CLL/SLL. Patients and Methods Specialty pharmacy electronic medical records were used to identify adults with CLL/SLL initiating 1L ibrutinib or acalabrutinib between 01/01/2018 and 11/30/2020. Adherence was measured by the proportion of days covered (PDC) and medication possession ratio (MPR) and was compared between cohorts using odds ratios (ORs) obtained from logistic regression models adjusted for baseline characteristics. Results Between 01/01/2018 and 11/30/2020, 1374 and 140 patients initiated ibrutinib and acalabrutinib, respectively. Based on PDC/MPR ≥80%, patients treated with once-daily ibrutinib were more likely to be adherent than those treated with twice-daily acalabrutinib (OR ranges: PDC: 1.04–1.76; MPR: 1.03–1.58). At 6 months, patients on ibrutinib had a 58–76% higher likelihood of staying adherent compared to patients on acalabrutinib (PDC: 75.9% for ibrutinib vs 63.6% for acalabrutinib, OR: 1.76, P=0.008; MPR: 76.8% vs 66.9%, OR: 1.58, P=0.036) with a similar trend noted for the entire line of treatment (LOT) (PDC: 53.0% vs 41.4%, OR: 1.53, P=0.021; MPR: 58.7% vs 47.1%, OR: 1.50, P=0.027). Conclusion In this real-world analysis, CLL/SLL patients initiating 1L once-daily ibrutinib had >50% higher treatment adherence than those initiating twice-daily acalabrutinib during their LOT. Given the importance of sustained adherence for disease control in CLL/SLL, dosing frequency may be an important consideration for patients and physicians.

[1]  G. Follows,et al.  Acalabrutinib ± obinutuzumab versus obinutuzumab + chlorambucil in treatment-naïve chronic lymphocytic leukemia: Five-year follow-up of ELEVATE-TN. , 2022, Journal of Clinical Oncology.

[2]  A. Deal,et al.  Impact of adherence to ibrutinib on clinical outcomes in real-world patients with chronic lymphocytic leukemia , 2022, Leukemia & lymphoma.

[3]  A. Jemal,et al.  Cancer statistics, 2022 , 2022, CA: a cancer journal for clinicians.

[4]  Shaun P. Forbes,et al.  Real-World Persistence and Time to Next Treatment With Ibrutinib in Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Including Patients at High Risk for Atrial Fibrillation or Stroke. , 2021, Clinical lymphoma, myeloma & leukemia.

[5]  M. Davids,et al.  Majic: A Phase 3 Prospective, Multicenter, Randomized, Open-Label Trial of Acalabrutinib Plus Venetoclax Versus Venetoclax Plus Obinutuzumab in Previously Untreated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma , 2021, Blood.

[6]  M. Hallek,et al.  Chronic lymphocytic leukemia: 2022 update on diagnostic and therapeutic procedures , 2021, American journal of hematology.

[7]  A. LaCasce,et al.  Acalabrutinib, venetoclax, and obinutuzumab as frontline treatment for chronic lymphocytic leukaemia: a single-arm, open-label, phase 2 study. , 2021, The Lancet. Oncology.

[8]  J. Pagel,et al.  Current and future treatment strategies in chronic lymphocytic leukemia , 2021, Journal of Hematology & Oncology.

[9]  Anqi Zhu,et al.  Impact of Adherence to Ibrutinib on Clinical Outcomes in Real-World Patients With Chronic Lymphocytic Leukemia , 2021, Journal of the advanced practitioner in oncology.

[10]  A. Mato,et al.  Healthcare resource utilization and costs associated with first-line ibrutinib compared to chemoimmunotherapy treatment among Medicare beneficiaries with chronic lymphocytic leukemia , 2020, Current medical research and opinion.

[11]  A. Wiestner,et al.  Ibrutinib for Chronic Lymphocytic Leukemia with TP53 Alterations. , 2020, The New England journal of medicine.

[12]  Á. Illés,et al.  ASCEND: Phase III, Randomized Trial of Acalabrutinib Versus Idelalisib Plus Rituximab or Bendamustine Plus Rituximab in Relapsed or Refractory Chronic Lymphocytic Leukemia. , 2020, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[13]  J. Byrd,et al.  Acalabrutinib with or without obinutuzumab versus chlorambucil and obinutuzumab for treatment-naive chronic lymphocytic leukaemia (ELEVATE-TN): a randomised, controlled, phase 3 trial , 2020, The Lancet.

[14]  C. Gillespie,et al.  Medication adherence, health care utilization, and spending among privately-insured adults with chronic conditions in the United States, 2010-2016. , 2020, The American journal of medicine.

[15]  K. Wada,et al.  Treatment patterns, adverse events, healthcare resource use and costs among commercially insured patients with mantle cell lymphoma in the United States , 2019, Cancer medicine.

[16]  J. Mielgo-Ayuso,et al.  Adherence to treatment and related factors among patients with chronic conditions in primary care: a cross-sectional study , 2019, BMC Family Practice.

[17]  T. Shanafelt,et al.  Ibrutinib-Rituximab or Chemoimmunotherapy for Chronic Lymphocytic Leukemia. , 2019, The New England journal of medicine.

[18]  Naveen Garg,et al.  Ibrutinib and Venetoclax for First-Line Treatment of CLL. , 2019, The New England journal of medicine.

[19]  Scott E. Smith,et al.  Ibrutinib Regimens versus Chemoimmunotherapy in Older Patients with Untreated CLL , 2018, The New England journal of medicine.

[20]  M. Hallek,et al.  Updated results from the phase 3 HELIOS study of ibrutinib, bendamustine, and rituximab in relapsed chronic lymphocytic leukemia/small lymphocytic lymphoma , 2018, Leukemia.

[21]  T. Kipps,et al.  Sustained efficacy and detailed clinical follow-up of first-line ibrutinib treatment in older patients with chronic lymphocytic leukemia: extended phase 3 results from RESONATE-2 , 2018, Haematologica.

[22]  E. Hagström,et al.  A systematic literature review comparing methods for the measurement of patient persistence and adherence , 2018, Current medical research and opinion.

[23]  Fernando Fernandez-Llimos,et al.  Economic impact of medication non-adherence by disease groups: a systematic review , 2018, BMJ Open.

[24]  E. Jaul,et al.  Age-Related Diseases and Clinical and Public Health Implications for the 85 Years Old and Over Population , 2017, Front. Public Health.

[25]  J. Byrd,et al.  Impact of ibrutinib dose adherence on therapeutic efficacy in patients with previously treated CLL/SLL. , 2017, Blood.

[26]  Jeffrey A Jones,et al.  Ibrutinib for patients with relapsed or refractory chronic lymphocytic leukaemia with 17p deletion (RESONATE-17): a phase 2, open-label, multicentre study. , 2016, The Lancet. Oncology.

[27]  T. Kipps,et al.  Ibrutinib as Initial Therapy for Patients with Chronic Lymphocytic Leukemia. , 2015, The New England journal of medicine.

[28]  J. Byrd,et al.  Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia. , 2014, The New England journal of medicine.

[29]  M. McGuire,et al.  Adherence and health care costs , 2014, Risk Management and Healthcare Policy.

[30]  Joseph Hanlon,et al.  Clinical consequences of polypharmacy in elderly , 2014, Expert opinion on drug safety.

[31]  Brian W. Ward,et al.  Prevalence of Multiple Chronic Conditions Among US Adults: Estimates From the National Health Interview Survey, 2010 , 2013, Preventing chronic disease.

[32]  P. Sorice,et al.  Patient Adherence and Persistence with Imatinib, Nilotinib, Dasatinib in Clinical Practice , 2013, PloS one.

[33]  D. Sobieraj,et al.  Dosing Frequency and Medication Adherence in Chronic Disease , 2012, Journal of managed care pharmacy : JMCP.

[34]  Bradley C Martin,et al.  Good and poor adherence: optimal cut-point for adherence measures using administrative claims data , 2009, Current medical research and opinion.

[35]  Marsha A Raebel,et al.  Measurement of Adherence in Pharmacy Administrative Databases: A Proposal for Standard Definitions and Preferred Measures , 2006, The Annals of pharmacotherapy.

[36]  J. Reginster,et al.  Adherence, patient preference and dosing frequency: understanding the relationship. , 2006, Bone.

[37]  M. Robin DiMatteo,et al.  Patient Adherence and Medical Treatment Outcomes: A Meta-Analysis , 2002, Medical care.

[38]  R. Greil,et al.  Ibrutinib plus obinutuzumab versus chlorambucil plus obinutuzumab in first-line treatment of chronic lymphocytic leukaemia (iLLUMINATE): a multicentre, randomised, open-label, phase 3 trial. , 2019, The Lancet. Oncology.