Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Jul 9:10:199-208.
doi: 10.2147/JBM.S202286. eCollection 2019.

Real-world experience of ibrutinib therapy in relapsed chronic lymphocytic leukemia: results of a single-center retrospective analysis

Elisabeth Nuttall  1   2 , Joanna Tung  3 , Ellie Trounce  3 , Rosalynd Johnston  2 , Timothy Chevassut  2   3
Affiliations

Real-world experience of ibrutinib therapy in relapsed chronic lymphocytic leukemia: results of a single-center retrospective analysis

Elisabeth Nuttall et al. J Blood Med. .

Abstract

Background: Ibrutinib is a Bruton's tyrosine-kinase (BTK) inhibitor that is approved as a second-line treatment in chronic lymphocytic leukemia (CLL). While recent trials have demonstrated impressive results for ibrutinib, there remains a paucity of real-world data on its use in the clinical setting.

Methods: In this single-center study carried out at Brighton and Sussex University Hospitals, we retrospectively compared outcomes in 38 patients with relapsed CLL who received ibrutinib versus those who received conventional first- and second-line therapies.

Results: Our results demonstrate improved progression-free survival (PFS, p=0.022) with ibrutinib versus conventional second-line therapies and survival comparable to conventional first-line therapies. However, there was a high frequency (81.6%) of adverse events associated with ibrutinib therapy, including 2 cases of death secondary to sepsis and a further 7 cases of discontinuation of treatment due to adverse events. We also identify del13q14.3 as an adverse predictor of response to ibrutinib with respect to both overall survival (p=0.014) and PFS (p=0.008), suggesting that these patients may be better suited to receiving the BCL2 inhibitor venetoclax.

Conclusion: Whilst there is robust evidence for improved outcomes with ibrutinib, we find that survival in patients with del13q14.3 is reduced and that the rate of adverse events and discontinuation in clinical practice is higher than anticipated from clinical trials.

Keywords: CLL; adverse events; chronic lymphocytic leukaemia; ibrutinib; real-world; relapsed.

PubMed Disclaimer

Conflict of interest statement

The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
(A) Overall survival with ibrutinib versus conventional second-line therapy; (B) progression-free survival with ibrutinib versus conventional second-line therapy; (C) overall survival with ibrutinib versus conventional first-line therapy; (D) progression-free survival with ibrutinib versus conventional first-line therapy.
Figure 2
Figure 2
(A) Overall survival with ibrutinib versus FCR and chlorambucil monotherapy, (B) progression-free survival with ibrutinib versus FCR and chlorambucil monotherapy. FCR, fludarabine, cyclophosphamide, rituximab.
Figure 3
Figure 3
(A) Progression-free survival with ibrutinib according to del17p and/or TP53 mutation status; (B) progression-free survival with ibrutinib according to del13q14.3 status.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Kantarjian H, Sawyers C, Hochhaus A, et al. Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia. N Engl J Med. 2002;346(9):645–652. doi:10.1056/NEJMoa011573 - DOI - PubMed
    1. Talpaz M, Silver RT, Druker BJ, et al. Imatinib induces durable hematologic and cytogenetic responses in patients with accelerated phase chronic myeloid leukemia: results of a phase 2 study. Blood. 2002;99(6):1928 LP–1937. doi:10.1182/blood.V99.6.1928 - DOI - PubMed
    1. Hochhaus A, Larson RA, Guilhot F, et al. Long-term outcomes of imatinib treatment for chronic myeloid leukemia. N Engl J Med. 2017;376(10):917–927. doi:10.1056/NEJMoa1609324 - DOI - PMC - PubMed
    1. Saouaf SJ, Mahajan S, Rowley RB, et al. Temporal differences in the activation of three classes of non-transmembrane protein tyrosine kinases following B-cell antigen receptor surface engagement. Proc Natl Acad Sci U S A. 1994;91(20):9524–9528. doi:10.1073/pnas.91.20.9524 - DOI - PMC - PubMed
    1. Brorson K, Brunswick M, Ezhevsky S, et al. xid affects events leading to B cell cycle entry. J Immunol. 1997;159(1):135–143. - PubMed