Drivers of Treatment Patterns in Patients with Chronic Lymphocytic Leukemia (CLL) Treated with B-Cell Receptor Inhibitors (BCRis) — a Medical Chart Review Study

Introduction: The treatment landscape for CLL has drastically changed in recent years with the approval of novel oral therapies, including inhibitors of the B cell receptor signaling pathways (BCRis). BCRis, including ibrutinib and idelalisib, have been associated with high and durable response rates and are widely used in clinical practice. Despite their efficacy, some patients stop BCRi therapy, and prior studies have demonstrated that intolerance was the primary reason in real-world practice (Mato et al, BLOOD 2016). This study evaluated reasons for treatment changes among CLL patients who stopped BCRi therapy.

Methods: Patient-level data were abstracted from charts and collected via an online questionnaire from 69 US oncologists/hematologists between January and March 2017. Data were collected for adult CLL patients who initiated a BCRi therapy and later exhibited one of the following treatment patterns: (1) switched from the BCRi to another anti-neoplastic regimen (Switched cohort), (2) discontinued the BCRi and remained untreated (Discontinued cohort), or (3) restarted the same BCRi after an interruption of ≥60 days (Restarted cohort). Patient demographics, clinical/treatment characteristics, and reasons for stopping and restarting the BCRi therapy were assessed for each cohort. All analyses were descriptive.

Results: Data were collected on 152 patients - 51 in the Switched cohort, 50 in the Discontinued cohort, and 51 in the Restarted cohort. Ibrutinib was the first BCRi used by 96% of patients; additionally, many patients received it as 1st-line therapy (63%, 86%, and 60% in the Switched, Discontinued, and Restarted cohorts, respectively). The majority of patients were male (67%), and the mean ages at CLL diagnosis were 65, 69, and 66 years for the Switched, Discontinued, and Restarted cohorts, respectively. Median time from BCRi initiation to stop was 7.0, 9.0, and 5.0 months in the aforementioned cohorts, respectively. Reasons for stopping BCRi therapy varied across the cohorts. Among patients in the Switched cohort, 80% switched due to disease progression, 14% due to adverse events (AEs)/comorbidities, and 6% for stem cell transplant. The regimens most commonly switched to were another BCRi-based regimen (41%), a chemotherapy-based regimen (41%), venetoclax (14%), a monoclonal antibody (2%), or an immunomodulating agent (2%). Among patients in the Discontinued cohort, reasons for stopping BCRi therapy were heterogeneous. Within this cohort, 46% stopped BCRi therapy because the patient was terminally ill, died, or was moved to best supportive care. These patients were generally older (mean 72 years), had more severe disease (70% had Rai stage III-IV at BCRi initiation), and had a high comorbidity burden. Median time to discontinuation for these patients was 5.6 months. The remaining 54% of patients in the Discontinued cohort stopped BCRi therapy due to low disease activity (24%), management of AEs/comorbidities (12%), or patient-requested drug holidays (18%). For these patients, median time to discontinuation was 11.1 months. Among patients in the Restarted cohort, the most common reasons for stopping BCRi therapy were patient-requested drug holidays (37%), AEs (31%), and economic reasons (10%). Median time from BCRi stop to restart was 3.1 months. Patients most commonly restarted BCRi therapy when the disease progressed (61%) or when they recovered from the AE (33%). Table 1 lists the most common AEs triggering an ibrutinib stop.

Conclusion: This study describes reasons for treatment changes in real-world practice among CLL patients who stopped or held BCRi therapy (mostly ibrutinib 1st-line therapy). Consistent with prior studies, the majority of patients stopped the BCRi due to intolerance or disease progression. Additionally, many patients stopped for other reasons including patient-requested drug holidays, some which were also attributed to intolerance. Results demonstrate varied clinical management of AEs and patient-requested drug holidays, suggesting a need for more evidence around these activities. Among patients who switched therapy, many switched due to disease progression. This may potentially indicate a sicker patient population than that in clinical trials. Finally, of patients who switched, over 40% switched to regimens whose effectiveness after a BCRi has not been studied prospectively and particularly after BCRi in the front line setting.

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