Adverse drug events associated with ibrutinib for the treatment of elderly patients with chronic lymphocytic leukemia

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.

Comparative Clinical Value of Pharmacologic Therapies for B-Cell Chronic Lymphocytic Leukemia: An Umbrella Analysis

“…Overall, 138 records were retrieved: 13 fully published MAs reported PFS or OS ( Table 1 and Table 2 ) [ 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 ] and 10 MAs reported safety outcomes ( Table 3 ) [ 8 , 9 , 11 , 15 , 18 , 19 , 20 , 21 , 22 , 23 ].…”

The Effect of Dietary Intervention With High-Oleocanthal and Oleacein Olive Oil in Patients With Early-Stage Chronic Lymphocytic Leukemia: A Pilot Randomized Trial

“…However, serious complications are observed in this type of therapy as they can produce toxicity especially in elderly patients such as those participating in our study. The clinical challenge is to be able to block the progress of the disease in its early stages so that there is no need for the patient to start any chemotherapeutic schedule (8,9,32).…”

A phase 2 study of ibrutinib maintenance following first‐line high‐dose methotrexate‐based chemotherapy for elderly patients with primary central nervous system lymphoma

“…Ibrutinib is an oral irreversible inhibitor of BTK that has demonstrated impressive tolerability and activity in a range of systemic B-cell lymphomas and is Food and Drug Administration approved for the treatment of chronic lymphocytic leukemia (CLL)/ small lymphocytic lymphoma, mantle cell lymphoma, marginal zone lymphoma, and Waldenstrom's macroglobulinemia. 21,36,37 As a result, an extensive experience with continued ibrutinib treatment, its toxicity and the management of its adverse events has been accumulated [37][38][39] and this experience includes the elderly. In addition, drug penetration across physiological barriers is an essential consideration and an effective treatment for PCNSL depends on drugs that cross the BBB and the blood-retinal barriers and thus penetrate the brain parenchyma, cerebrospinal fluid (CSF) and the intraocular compartments.…”