Adverse drug events associated with ibrutinib for the treatment of elderly patients with chronic lymphocytic leukemia: A systematic review and meta-analysis of randomized trials - PubMed (original) (raw)
Meta-Analysis
Adverse drug events associated with ibrutinib for the treatment of elderly patients with chronic lymphocytic leukemia: A systematic review and meta-analysis of randomized trials
Yanhua Zhou et al. Medicine (Baltimore). 2019 Aug.
Abstract
Background: Chronic lymphocytic leukemia (CLL) is a rare hematological malignancy classified in the non-Hodgkin's lymphoma category. Ibrutinib, a first-in-class Bruton tyrosine kinase inhibitor has been approved for use in the treatment of CLL. This drug has shown beneficial effects including a higher overall response rate, sustained remissions, and a tolerable toxicity level. In this meta-analysis, we aimed to compare the adverse drug events which were associated with the use of ibrutinib for the treatment of patients with CLL.
Methods: A careful search was carried out through the Cochrane Central, EMBASE, MEDLINE (PubMed), and through www.ClinicalTrials.com. The following criteria for inclusion were considered: Both randomized trials and observational cohorts; Studies comparing the adverse drug events observed with the use of ibrutinib versus a control group for the treatment of CLL. The RevMan software (version 5.3) was used to carry out this analysis and the analyzed data were represented by risk ratios (RR) and 95% confidence intervals (CI).
Results: A total number of 2456 participants with CLL were included in this analysis. One thousand one hundred thirteen participants were treated with ibrutinib whereas the remaining 1343 participants were assigned to the control (non-ibrutinib) group. Results of this current analysis showed Ibrutinib not to be associated with significantly higher risk of anemia (RR: 0.90, 95% CI: 0.67-1.21; P = .49), thrombocytopenia (RR: 0.61, 95% CI: 0.32-1.14; P = .12), neutropenia (RR: 0.50, 95% CI: 0.25-1.00; P = .05), and febrile neutropenia (RR: 0.89, 95% CI: 0.32-2.49; P = .83) in these patients with CLL. The risk for respiratory tract infection was also similarly manifested (RR: 1.01, 95% CI: 0.78-1.30; P = .96). However, ibrutinib was associated with a high risk of abdominal manifestations in comparison to the control group (RR: 1.62, 95% CI: 1.32-2.00; P = .00001). The risk for diarrhea was also significantly higher in the Ibrutinib group (RR: 2.14, 95% CI: 1.44-3.17; P = .0002).
Conclusions: During the treatment of CLL, ibrutinib was not associated with significantly higher risks of anemia, thrombocytopenia, or neutropenia compared to the control group. However, abdominal manifestations were significantly higher with ibrutinib. Advanced phase trials should further confirm this hypothesis.
Figures
Figure 1
Flow diagram showing the study selection for inclusion in this meta-analysis.
Figure 2
Forest plot demonstrating the adverse drug events observed with ibrutinib versus the control group for the treatment of patients with chronic lymphocytic leukemia (Part I).
Figure 3
Forest plot demonstrating the adverse drug events observed with ibrutinib versus the control group for the treatment of patients with chronic lymphocytic leukemia (Part II).
Figure 4
Forest plot demonstrating the adverse drug events observed with ibrutinib versus the control group for the treatment of patients with chronic lymphocytic leukemia (Part III).
Figure 5
Funnel plot showing publication bias.
Similar articles
- Long-term safety of single-agent ibrutinib in patients with chronic lymphocytic leukemia in 3 pivotal studies.
Coutre SE, Byrd JC, Hillmen P, Barrientos JC, Barr PM, Devereux S, Robak T, Kipps TJ, Schuh A, Moreno C, Furman RR, Burger JA, O'Dwyer M, Ghia P, Valentino R, Chang S, Dean JP, James DF, O'Brien SM. Coutre SE, et al. Blood Adv. 2019 Jun 25;3(12):1799-1807. doi: 10.1182/bloodadvances.2018028761. Blood Adv. 2019. PMID: 31196847 Free PMC article. Clinical Trial. - Ibrutinib as Initial Therapy for Patients with Chronic Lymphocytic Leukemia.
Burger JA, Tedeschi A, Barr PM, Robak T, Owen C, Ghia P, Bairey O, Hillmen P, Bartlett NL, Li J, Simpson D, Grosicki S, Devereux S, McCarthy H, Coutre S, Quach H, Gaidano G, Maslyak Z, Stevens DA, Janssens A, Offner F, Mayer J, O'Dwyer M, Hellmann A, Schuh A, Siddiqi T, Polliack A, Tam CS, Suri D, Cheng M, Clow F, Styles L, James DF, Kipps TJ; RESONATE-2 Investigators. Burger JA, et al. N Engl J Med. 2015 Dec 17;373(25):2425-37. doi: 10.1056/NEJMoa1509388. Epub 2015 Dec 6. N Engl J Med. 2015. PMID: 26639149 Free PMC article. Clinical Trial. - Phase I study of ibrutinib in Japanese patients with treatment-naïve chronic lymphocytic leukemia/small lymphocytic lymphoma.
Shibayama H, Teshima T, Choi I, Hatake K, Sekiguchi N, Yoshinari N. Shibayama H, et al. J Clin Exp Hematop. 2019;59(4):179-186. doi: 10.3960/jslrt.19023. J Clin Exp Hematop. 2019. PMID: 31866619 Free PMC article. Clinical Trial. - Indirect Treatment Comparisons of Ibrutinib Versus Physician's Choice and Idelalisib Plus Ofatumumab in Patients With Previously Treated Chronic Lymphocytic Leukemia.
Sorensen S, Wildgust M, Sengupta N, Trambitas C, Diels J, van Sanden S, Xu Y, Dorman E. Sorensen S, et al. Clin Ther. 2017 Jan;39(1):178-189.e5. doi: 10.1016/j.clinthera.2016.12.001. Epub 2017 Jan 3. Clin Ther. 2017. PMID: 28062113 Review. - Risk of Bleeding Associated With Ibrutinib in Patients With B-Cell Malignancies: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Wang J, Zhao A, Zhou H, Zhu J, Niu T. Wang J, et al. Front Pharmacol. 2020 Nov 20;11:580622. doi: 10.3389/fphar.2020.580622. eCollection 2020. Front Pharmacol. 2020. PMID: 33658926 Free PMC article. Review.
Cited by
- Bruton's Tyrosine Kinase Inhibitors (BTKIs): Review of Preclinical Studies and Evaluation of Clinical Trials.
Rozkiewicz D, Hermanowicz JM, Kwiatkowska I, Krupa A, Pawlak D. Rozkiewicz D, et al. Molecules. 2023 Mar 6;28(5):2400. doi: 10.3390/molecules28052400. Molecules. 2023. PMID: 36903645 Free PMC article. Review. - Comparative Clinical Value of Pharmacologic Therapies for B-Cell Chronic Lymphocytic Leukemia: An Umbrella Analysis.
Marchetti M, Rivela P, Bertassello C, Canicattì M. Marchetti M, et al. J Clin Med. 2022 Mar 28;11(7):1868. doi: 10.3390/jcm11071868. J Clin Med. 2022. PMID: 35407474 Free PMC article. Review. - The Effect of Dietary Intervention With High-Oleocanthal and Oleacein Olive Oil in Patients With Early-Stage Chronic Lymphocytic Leukemia: A Pilot Randomized Trial.
Rojas Gil AP, Kodonis I, Ioannidis A, Nomikos T, Dimopoulos I, Kosmidis G, Katsa ME, Melliou E, Magiatis P. Rojas Gil AP, et al. Front Oncol. 2022 Jan 21;11:810249. doi: 10.3389/fonc.2021.810249. eCollection 2021. Front Oncol. 2022. PMID: 35127522 Free PMC article. - Association of MTHFR C677T and A1298C Polymorphisms with Susceptibility to Chronic Lymphocytic Leukemia: A Systematic Review and Meta-Analysis.
Raoufi A, Rahimi Kelarijani B, Ahadi HR, Hassani Derakhshandeh B, Nooroollahzadeh Z, Hajifathali A. Raoufi A, et al. Iran J Public Health. 2021 Jan;50(1):83-92. doi: 10.18502/ijph.v50i1.5074. Iran J Public Health. 2021. PMID: 34178766 Free PMC article. Review.
References
- Eichhorst B, Dreyling M, Robak T, Hallek M. ESMO Guidelines Working Group. Chronic lymphocytic leukemia: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 2011;22 Suppl 6:vi50–4. - PubMed
- Scarfò L, Ferreri AJ, Ghia P. Chronic lymphocytic leukaemia. Crit Rev Oncol Hematol 2016;104:169–82. - PubMed
- Karakosta M, Delicha EM, Kouraklis G, Manola KN. Association of various risk factors with chronic lymphocytic leukemia and its cytogenetic characteristics. Arch Environ Occup Health 2016;71:317–29. - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources