Three-year follow-up of treatment-naïve and previously treated patients with CLL and SLL receiving single-agent ibrutinib

Abstract

Ibrutinib is an orally administered inhibitor of Bruton tyrosine kinase that antagonizes B-cell receptor, chemokine, and integrin-mediated signaling. In early-phase studies, ibrutinib demonstrated high response rates and prolonged progression-free survival (PFS) in chronic lymphocytic leukemia (CLL). The durable responses observed with ibrutinib relate in part to a modest toxicity profile that allows the majority of patients to receive continuous therapy for an extended period. We report on median 3-year follow-up of 132 patients with symptomatic treatment-naïve and relapsed/refractory CLL or small lymphocytic lymphoma. Longer treatment with ibrutinib was associated with improvement in response quality over time and durable remissions. Toxicity with longer follow-up diminished with respect to occurrence of grade 3 or greater cytopenias, fatigue, and infections. Progression remains uncommon, occurring primarily in some patients with relapsed del(17)(p13.1) and/or del(11)(q22.3) disease. Treatment-related lymphocytosis remains largely asymptomatic even when persisting >1 year and does not appear to alter longer-term PFS and overall survival compared with patients with partial response or better. Collectively, these data provide evidence that ibrutinib controls CLL disease manifestations and is well tolerated for an extended period; this information can help direct potential treatment options for different subgroups to diminish the long-term risk of relapse.

© 2015 by The American Society of Hematology.

Figures

Figure 1

Serial assessment of adverse events over time. (A) Grade ≥3 AEs by time to event onset from first dose date. The dashed line denotes a 5% rate; x-axis maximum is 50%. (B) Frequency of grade ≥3 AEs by TN or R/R status.

Figure 2

Response to ibrutinib over time. (A) Median percent change from baseline in the ALC and the sum of the products of lymph node diameters (SPD) in all patients, showing 95% confidence intervals for all patients. (B) Curves for cumulative best response (CR, PR, and PR-L) for all patients (N = 132). Results for TN patients (n = 31) are shown in C and D. Results for R/R patients (n = 101) are shown in E and F.

Figure 3

Hemoglobin levels and platelet counts in all treated patients with baseline anemias and thrombocytopenias, respectively.

Figure 4

PFS. (A) Kaplan-Meier curves of PFS in TN and R/R patients. (B) Kaplan-Meier curves of PFS in patients with del(17p) or del(11q) or without del(17p) or del(11q). (C) Kaplan-Meier curves of PFS from day 365 in patients who achieved CR and PR or PR-L within the first 364 days on study.

Figure 5

OS. (A) Kaplan-Meier curves of OS in TN and R/R patients. (B) Kaplan-Meier curves of OS in patients with del(17p) or del(11q) or without del(17p) or del(11q).