Long-Term Outcomes of Ibrutinib Therapy in CLL

To further define the long-term prognosis of patients treated with BTK, long-term follow-up data of a phase 2 study (NCT01500733) that evaluated the efficacy, safety, and depth of response of ibrutinib therapy in patients with chronic lymphocytic leukemia (CLL) were analyzed; these data were presented at the 2023 American Society of Hematology annual meeting and summarized here.

The study enrolled patients with high-risk CLL (defined by TP53 alterations or age ≥65 years-old). Eligible patients received ibrutinib 420 mg orally once daily until disease progression or intolerable side effects. Response assessments were performed annually (with CT scans up to 5 years and physical exam thereafter). Minimal residual disease (MRD) assessments were done annually with peripheral blood flow cytometry; undetectable MRD (uMRD) was defined as <1 CLL cell per 10,000 leukocytes. At data cut-off for this analysis (December 31, 2022), median follow-up was 113 months for progression-free survival (PFS) and 117 months for overall survival (OS).

A total of 84 patients were evaluable for analysis. In the TP53 cohort, one-third of patients were treatment-naïve, in the age ≥65 years cohort 53% were treatment-naïve. Of patients with a TP53 mutation, Median PFS was 85.9 months in both cohorts. Median PFS was significantly shorter in patients with TP53 alterations versus without (67.3 months vs not reached, P=.004) and in relapsed disease versus frontline (49 months vs 108 months, P=.016). The OS at 117 months was 61.6% in total cohort, 73.8% in treatment-naïve cohort, and 54.1% in TP53 alteration cohort. In frontline ibrutinib-treated patients with TP53 alterations (N=34), the median PFS was 81 months and OS at 117 months was 69.7%.

In the total cohort, uMRD was achieved in 13 (15.4%) patients; median time to uMRD was 5 years. Of these, the majority also achieved a complete response (CR, n=10). In the progression-free cohort, 8 patients showed sustained uMRD for 1-6 years including one patient who was not receiving any CLL-directed therapy for 4 years.

The adverse event (AE) analysis was consistent with previously reported data. At the time of analysis, 69 (82%) patients had discontinued ibrutinib therapy. The most common reasons for treatment discontinuation were progressive disease (44.0%) and treatment-emergent adverse events (TEAEs; 32.1%). TEAEs leading to discontinuation included cardiac AEs (n=8), 7 secondary cancers (n=7), infections (n=4), dementia (n=3), pleural effusions (n=2), and other AEs (n=3).

These results confirmed the long-term prognosis of ibrutinib-treated patients with CLL, particularly those with TP53 alterations.

Source:

Itsara A, Sun C, Bryer E, et al. Long-term outcomes in chronic lymphocytic leukemia treated with ibrutinib: 10-year follow-up of a phase 2 study. Presented at the 65th American Society of Hematology (ASH) Annual Meeting & Exposition, December 9-12, 2023; San Diego, CA: Abstract 201.