TY - JOUR
T1 - Analysis of Efficacy and Tolerability of Bruton Tyrosine Kinase Inhibitor Ibrutinib in Various B-cell Malignancies in the General Community
T2 - A Single-center Experience
AU - Ali, Naveed
AU - Malik, Faizan
AU - Jafri, Syed Imran Mustafa
AU - Naglak, Mary
AU - Sundermeyer, Mark
AU - Pickens, Peter V.
N1 - Publisher Copyright:
© 2017
PY - 2017/7
Y1 - 2017/7
N2 - Ibrutinib, a novel Bruton tyrosine kinase inhibitor, has revolutionized the treatment of various B-cell malignancies. In this retrospective study, we analyzed the data of 45 patients with various B-cell malignancies to determine ibrutinib's clinical efficacy and adverse effects in a real-world setting. Results showed an excellent efficacy and a favorable toxicity but a higher incidence of atrial fibrillation. Background Ibrutinib, an irreversible inhibitor of Bruton tyrosine kinase (BTK), is a novel drug that has shown significant efficacy and survival benefit for treatment of various B-cell malignancies. The primary objective of the present study was to investigate the efficacy of ibrutinib therapy in various B-cell malignancies in the general community. The secondary objectives included studying the adverse effects, ibrutinib-induced peripheral lymphocytosis, and effect on immunoglobulin levels. Patients and Methods The present study was a retrospective observational cohort analysis conducted at Abington Jefferson Health. The clinical response was determined from the hematologist's assessment and evaluated independently using the response criteria for each B-cell malignancy. Adverse effects were graded according to the Common Terminology Criteria for Adverse Events, version 4.0. The Wilcoxon signed-rank test was used to compare immunoglobulin levels before and after ibrutinib. Forty five patients with B-cell malignancies and receiving ibrutinib therapy were eligible. Results The median age was 73 years (range, 49-96 years), and 84.4% of the patients had received ≥ 1 previous therapy. The best overall response rate of all cohorts combined was 63.8%. The greatest overall response rate was observed in patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (76.1%), followed by those with Waldenström macroglobulinemia (75%). Of the 45 patients, 88.9% experienced adverse effects. Antiplatelet activity of ibrutinib was most commonly observed (30.5%). Of note, 5 patients (11%) developed new-onset atrial fibrillation after drug initiation. Peripheral lymphocytosis after drug initiation was observed in most patients, with a peak level at 1 month (median lymphocyte count, 2.7 × 103 cells/μL). Although the IgG levels at 3, 6, and 12 months had decreased (P = .01 for all) compared with the levels before ibrutinib, the IgA levels had not increased at 3, 6, 12, and 24 months (P = .6, P = .5, P = .3, and P = .9, respectively). Conclusion Ibrutinib is a highly effective and tolerable drug for B-cell malignancies in the general community. In contrast to the previously reported rate of 5% to 7%, we observed a higher rate (11%) of atrial fibrillation, which might have resulted from the smaller sample size in the present study and the multiple comorbidities. Nonetheless, this treatment-limiting side effect requires further elucidation. Paradoxical lymphocytosis at the outset of therapy was a common and benign finding. In conjunction with the reported trials, the IgG levels decreased in the first year of continued therapy. However, the IgA levels did not increase, even after 2 years of therapy.
AB - Ibrutinib, a novel Bruton tyrosine kinase inhibitor, has revolutionized the treatment of various B-cell malignancies. In this retrospective study, we analyzed the data of 45 patients with various B-cell malignancies to determine ibrutinib's clinical efficacy and adverse effects in a real-world setting. Results showed an excellent efficacy and a favorable toxicity but a higher incidence of atrial fibrillation. Background Ibrutinib, an irreversible inhibitor of Bruton tyrosine kinase (BTK), is a novel drug that has shown significant efficacy and survival benefit for treatment of various B-cell malignancies. The primary objective of the present study was to investigate the efficacy of ibrutinib therapy in various B-cell malignancies in the general community. The secondary objectives included studying the adverse effects, ibrutinib-induced peripheral lymphocytosis, and effect on immunoglobulin levels. Patients and Methods The present study was a retrospective observational cohort analysis conducted at Abington Jefferson Health. The clinical response was determined from the hematologist's assessment and evaluated independently using the response criteria for each B-cell malignancy. Adverse effects were graded according to the Common Terminology Criteria for Adverse Events, version 4.0. The Wilcoxon signed-rank test was used to compare immunoglobulin levels before and after ibrutinib. Forty five patients with B-cell malignancies and receiving ibrutinib therapy were eligible. Results The median age was 73 years (range, 49-96 years), and 84.4% of the patients had received ≥ 1 previous therapy. The best overall response rate of all cohorts combined was 63.8%. The greatest overall response rate was observed in patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (76.1%), followed by those with Waldenström macroglobulinemia (75%). Of the 45 patients, 88.9% experienced adverse effects. Antiplatelet activity of ibrutinib was most commonly observed (30.5%). Of note, 5 patients (11%) developed new-onset atrial fibrillation after drug initiation. Peripheral lymphocytosis after drug initiation was observed in most patients, with a peak level at 1 month (median lymphocyte count, 2.7 × 103 cells/μL). Although the IgG levels at 3, 6, and 12 months had decreased (P = .01 for all) compared with the levels before ibrutinib, the IgA levels had not increased at 3, 6, 12, and 24 months (P = .6, P = .5, P = .3, and P = .9, respectively). Conclusion Ibrutinib is a highly effective and tolerable drug for B-cell malignancies in the general community. In contrast to the previously reported rate of 5% to 7%, we observed a higher rate (11%) of atrial fibrillation, which might have resulted from the smaller sample size in the present study and the multiple comorbidities. Nonetheless, this treatment-limiting side effect requires further elucidation. Paradoxical lymphocytosis at the outset of therapy was a common and benign finding. In conjunction with the reported trials, the IgG levels decreased in the first year of continued therapy. However, the IgA levels did not increase, even after 2 years of therapy.
KW - Atrial fibrillation
KW - BTK
KW - Bleeding
KW - Immunoglobulins
KW - Peripheral lymphocytosis
UR - http://www.scopus.com/inward/record.url?scp=85026498711&partnerID=8YFLogxK
U2 - 10.1016/j.clml.2017.02.011
DO - 10.1016/j.clml.2017.02.011
M3 - Article
C2 - 28760303
AN - SCOPUS:85026498711
SN - 2152-2650
VL - 17
SP - S53-S61
JO - Clinical Lymphoma, Myeloma and Leukemia
JF - Clinical Lymphoma, Myeloma and Leukemia
ER -