1204 - Real-World Characteristics and Outcomes of Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Treated With Long-Term Ibrutinib: Results From the Prospective, Observational informCLL Registry

Introduction: Recent analyses from the phase 3 RESONATE-2 study in patients with previously untreated chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) showed that more than half of patients treated with ibrutinib continued to benefit from long-term ibrutinib therapy regardless of baseline characteristics, with sustained efficacy benefits (Woyach. Cancers 2023). Limited data are available on patient characteristics associated with long-term ibrutinib treatment in the real-world setting. The informCLL registry is a large, US-based, prospective, observational registry of patients who initiated FDA-approved treatment for CLL/SLL in the era after approval of ibrutinib and represents an opportunity to explore real-world outcomes in patients treated primarily in community-based practices. Here, we present the real-world characteristics and outcomes of previously untreated patients with CLL who received long-term (≥3 years) first-line (1L) treatment with ibrutinib on informCLL.

Methods: Patients with CLL/SLL who initiated FDA-approved treatment (within ±45 days of enrollment) were enrolled between October 2015 and June 2019. For this analysis, we evaluated the baseline demographics and characteristics, time to next treatment (TTNT), OS, and safety among the cohort of patients treated with 1L ibrutinib for ≥3 years. Multivariate logistic regression analysis was performed to determine baseline factors associated with the likelihood of receiving long-term ibrutinib (variables included time from initial diagnosis to 1L therapy, age, sex, race, insurance type, geographic region, ECOG status, Rai stage, comorbidity burden, other prior malignancy, FISH testing, del[17p]) by evaluating patients with 1L ibrutinib for ≥3 years compared to all others. TTNT and OS were estimated by Kaplan-Meier methods. Safety was assessed by rates of serious adverse events (AEs) and AEs leading to treatment discontinuation.

Results: A total of 1459 eligible patients were enrolled to informCLL; 854 patients were treated in the 1L setting, including 383 who received 1L ibrutinib therapy. Median duration of 1L ibrutinib was 24.0 months (range, 0.2−61.1) with a median follow-up of 31.4 months (range, 1.2−66.1); 42% of patients were receiving ongoing ibrutinib at study exit, including 82 patients who exited the study prior to 3 years of treatment due to study closure. Overall, 100 patients received ≥3 years of ibrutinib therapy, with a median treatment duration of 43.7 months. Baseline characteristics were largely similar between patients who received ≥3 years and those who received < 3 years of ibrutinib (Table 1). In univariate analysis, there was a trend toward patients with high comorbidity burden (CCI ≥2) being less likely to receive ibrutinib for ≥3 years, although these findings were not statistically significant. In both univariate and multivariate analyses, no factors were significantly associated with likelihood of receiving ≥3 years of ibrutinib. With a median follow-up of 47.2 months in patients who received ibrutinib for ≥3 years, the estimated rate without next-line therapy was 93.9% at 48 months and 90.8% at 54 months; estimated OS rate was 96.5% at 48 months and 94.0% at 54 months. In patients treated with ≥3 years of ibrutinib, serious AEs occurred in 32 patients (32%); the most common serious AEs (reported in >3 patients) included pneumonia (n=5) and atrial fibrillation (n=4). AEs leading to ibrutinib treatment discontinuation occurred in 7 patients (7%) and included mucosal inflammation, increased hepatic enzyme, myalgia, Richter syndrome, confusional state, and palmar-plantar erythrodysesthesia syndrome (n=1 each). AEs led to ibrutinib dose modification in 19 patients (19%), most commonly due to fatigue (n=6). Among these 19 patients, AEs leading to first dose reduction tended to occur within the first year of ibrutinib, with a median treatment duration of at least 3 years after first dose reduction and 74% (14/19 patients) remaining on treatment at end of study (Table 2).

Conclusion: Analyses from informCLL show sustained TTNT and OS benefits in patients treated with ≥3 years of ibrutinib, with low rates of AEs leading to treatment discontinuation beyond 3 years and no new AEs observed. Baseline characteristics were similar between patients treated with 1L ibrutinib for ≥3 and those treated for < 3 years. Consistent with the recent findings from the RESONATE-2 study, patients with dose modifications were also able to receive long-term therapy with 1L ibrutinib in this real-world registry. Together, these results suggest that patients with CLL representing a broad range of baseline characteristics can receive and benefit from long-term therapy with 1L ibrutinib in the real-world setting.