Small Elderly CLL Population Discontinues Venetoclax/Obinutuzumab Treatment

"Patients discontinuing treatment before completing the prescribed 12 cycles were older, were more likely to use corticosteroids at baseline, and had poorer renal function," according to the authors of a real-world descriptive analysis published in Current Medical Research and Opinion.

Investigators reported that a small proportion of elderly patients with chronic lymphocytic leukemia (CLL) or small lymphocytic leukemia (SLL) discontinued frontline treatment with venetoclax (Venclexta) plus obinutuzumab (Gazyva) before completing 12 treatment cycles, according to findings from a real-world descriptive analysis published in Current Medical Research and Opinion.

With a median follow-up of 16.2 months, 16.8% of patients discontinued treatment with venetoclax plus obinutuzumab before completing 12 cycles, and 68.1% completed at least 12 cycles of treatment. Of those who completed at least 12 cycles, 29.9% completed 15 or more cycles.

Investigators noted that 46.9% of patients discontinued treatment for more than 120 days or switched to alternative therapy before, on, or following the point they were expected to complete frontline therapy. Additionally, the median time to treatment discontinuation (TTD) was 13.8 months.

The mean age of patients who discontinued first-line venetoclax plus obinutuzumab before 12 cycles was 70.4±9.4 years compared with 65.1±10.4 years among patients who completed all 12 prescribed cycles of therapy. Additionally, 21.1% of patients who discontinued therapy had baseline use of corticosteroids compared with 15.6% of patients who completed all treatment cycles. Investigators identified a higher proportion of patients with poor renal function, defined as a creatinine clearance of less than 60 mL per minute, among those who discontinued treatment (36.8%) compared with those who completed all cycles (13.0%).

The rates of patients using corticosteroids, anti-hyperuricemic agents, and anti-emetics in the first 60 days following initiation of venetoclax plus obinutuzumab were 100.0%, 78.8%, and 52.2%, respectively; from day 61 and beyond, the utilization rates for each respective treatment were 67.0%, 45.5%, and 33.9%. Additionally, 3.5% of patients had a tumor lysis syndrome (TLS) diagnosis during treatment initiation compared with 0.0% in the post-initiation phase.

“Patients discontinuing treatment before completing the prescribed 12 cycles were older, were more likely to use corticosteroids at baseline, and had poorer renal function,” the study authors wrote. “Furthermore, utilization of anti-hyperuricemics and anti-emetics was higher during the initiation than post-initiation phase, suggesting closer monitoring during treatment initiation, potentially for TLS mitigation and management.”

Investigators of this real-world study used a nationwide electronic health record-derived database to evaluate outcomes of adult patients who received first-line venetoclax plus obinutuzumab for CLL or SLL between April 2016 and July 2020.

Investigators assessed treatment utilization patterns and incidence of TLS during the initiation phase, defined as the first 60 days after patients began frontline therapy, and the post-initiation phase consisting of the remaining duration of therapy. TTD was defined as the time from treatment initiation to the earliest stopping of treatment due to a gap in treatment for more than 120 days or the day prior to switching to an additional line of therapy.

Patients 18 years and older with a confirmed diagnosis of CLL or SLL and at least 28 days of clinical activity after initiating frontline therapy were included in the study. Those who had incomplete line of therapy information in the database or at least 1 diagnosis for end-stage renal disease before initiating frontline therapy were not included in the study.

Among 113 patients who received frontline venetoclax plus obinutuzumab, most began treatment in 2020 (59.3%) and received treatment in a community setting (89.4%). Additionally, most had baseline use of anti-hyperuricemics (63.7%), Rai stage 0 disease (30.1%), and an ECOG performance status of 0 (46.9%).

“Further research with longer follow-up to assess long-term outcomes of [venetoclax plus obinutuzumab] treatment after early discontinuation is warranted,” the study authors concluded.

Reference

Lu X, Emond B, Qureshi ZP, et al. Real-world time to discontinuation of first-line venetoclax + obinutuzumab in chronic lymphocytic leukemia/small lymphocytic lymphoma. Curr Med Res Opin. Published online August 21, 2023. doi:10.1080/03007995.2023.2243815