Efficacy and Safety of Ibrutinib in Elderly Patients with Chronic Lymphocytic Leukemia

Background: For most of the elderly chronic lymphocytic leukemia (CLL) patients, treatment outcome focus on achievement of clinical response, relief of symptoms and prolongation of life expectancy, but comorbidities, frailty and reduced functional status in elderly patients make the standard treatments intolerable and less efficacious. Single agent Ibrutinib (Ibr), an inhibitor of oral Bruton's tyrosine kinase, is approved for the front-line treatment of patients with CLL by Chinese Food and Drug Administration (CFDA) in 2017.

Objectives: This study evaluated effeicacy and safety of single agent Ibrutinib in elderly patients with treatment-naive chronic lymphocytic leukemia for 2 years in our center.

Methods: Patients over 65 years old with previously untreated CLL/SLL (n = 37) were received Ibr 420 mg once daily continuously until disease progression or unacceptable toxicity. We examined baseline demographics/disease characteristics, endpoints included overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety in patients with CLL receiving ibrutinib.

Results: 37 CLL patients over 65 years old were enrolled and treated with from June 2017 to May 2019 in our center. The median follow-up was 19.4 months (range, 0.8-31.6 months). Their F/M ratio was 16/21 and the median age of the enrolled population was 77.3 years (range, 65.4-92.7 years). 31 (83.8%) patients had an Eastern Cooperative Oncology Group performance status of 0-1. In these patients, 18/34 (52.9%) had del17p and/or TP53 mutation, and 20/30 (66.7%) had unmutated IGHV. With Ibr, Overall response rate (ORR) was 91.9%; complete response (CR) was 8.0%, partial response (PR) was 51.4%, and PR with lymphocytosis (PRwL) was 32.4%. Median progress free survival (PFS) was 17.3 months (95% CI, 14.3-24.0); PFS rates at 12 and 24 months were 87.1% and 74.0%, respectively. Median PFS with ibrutinib was comparable in pts with/without del17p and/or TP53 mutation (16.4 [95% CI, 14.3-NE] vs 14.5 months [95% CI, 13.9-NE]) and with unmutated/mutated IGHV (16.8 [95% CI, 12.1-22.8] vs 19.7 months [95% CI, 14.3-23.0]). Overall survival (OS) rates were 95.8% and 86.8% at 12 and 24 months, respectively. Median time to best response was 4.8 months (95% confidence interval [CI], 3.7-5.5). With median follow-up of 19.4 months, 21.6% (8/37) of pts had progressed or died. In the safety analysis, the most common serious adverse events (AEs) were recorded in 6 patients include neutropenia (4 pts), pneumonia (3 pts), hypertension (3 pts), anemia (2 pts), hyponatremia (2 pts), and atrial fibrillation (2 pts). AEs of any grade leading to ibr discontinuation occurred in 3 pts over time.

Conclusions: In total, single agent ibrutinib was well tolerated and yielded high response rates, including for pts with high-risk genomic features, that were durable and deepened over time in treatment-naive elderly patients with CLL. Ibrutinib also had sustained PFS and OS benefit. Safety profile was acceptable and the most serious adverse events were neutropenia, pneumonia, hypertension, anemia, hyponatremia, and atrial fibrillation.