2007 - Real-World Duration of Venetoclax Treatment for Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma

Introduction: Venetoclax (V) is an approved fixed-duration treatment for patients with chronic lymphocytic leukemia and small lymphocytic lymphoma (CLL/SLL), either as a 12-cycle regimen (~12 months) in combination with obinutuzumab (O) in the first-line (1L) setting or as a 24-cycle regimen (~24 months) in combination with rituximab (R) in the relapsed/refractory (R/R) setting. Our objective was to analyze real-world treatment patterns of V+O in 1L and V+R in R/R settings in patients with CLL/SLL in the United States.

Methods: A retrospective cohort analysis was conducted using the IQVIA PharMetrics® Plus database to identify patients aged ≥18 years treated with V+O (1L cohort; May 2019 to September 2021) or V+R (R/R cohort; June 2018 to September 2021). The start of the treatment regimen was defined as the index date. All patients were required to have ≥1 diagnosis code for CLL/SLL, 12 months of continuous enrollment (CE) prior to the index date, and ≥3 months of CE after the index date. Duration of treatment (DoT) was defined as time from index date to the earliest of either treatment discontinuation (defined as a ≥60-day gap in V prescription refills) or censoring (defined as end of follow-up). Fixed-duration treatment cycle was defined as 12- or 24-cycle dosing, corresponding to days 336−364 for the 1L setting and days 707−735 for the R/R setting, based on the dosing schedule plus 28 days. Kaplan-Meier analysis was used to estimate the probability of remaining on treatment for the 1L and R/R cohorts.

Results: A total of 116 patients in 1L setting (mean age, 62.3 years; 73.3% male) and 145 patients in R/R setting (mean age, 64.2 years; 73.8% male) were identified; 48.3% of patients in the R/R cohort had prior targeted therapy. The median (95% CI) DoT in patients treated with V+O (n=115) was 12.4 (11.5, 13.4) months over a median follow-up of 11.4 months; the probability of remaining on treatment at 6, 12, and 18 months was 80.6%, 56.4%, and 20.2%, respectively. The median (95% CI) DoT in patients treated with V+R (n=133) was 24.5 (13.4, 25.2) months over a median follow-up of 15.5 months; the probability of remaining on treatment at 12, 24, and 36 months was 66.0%, 53.8%, and 19.0%, respectively. Among patients treated with V+O, 47.8% (55/115) of patients had ≥12 months of follow-up (Table). Of the 55 patients with ≥12 months of follow-up, 9.1% had fixed cycles and 38.2% discontinued early (median DoT: 4.6 months; mean DoT: 5.1 months). Among patients treated with V+R, 29.3% (39/133) of patients had ≥24 months of follow-up. Of the 39 patients with ≥24 months of follow-up, 5.1% had fixed cycles and 46.2% discontinued early (median DoT: 7.1 months; mean DoT: 8.4 months). Among the patients treated for < 12 months with V+O (n=30) and < 24 months with V+R (n=48), the DoT was much shorter than the fixed-dosing schedule (mean DoT [SD]: 4.9 [3.2] and 6.8 [4.8] months, respectively) over a median follow-up of 17.8 and 17.9 months, respectively. Among the patients treated for >12 months with V+O (n=29) and >24 months with V+R (n=19), the DoT was slightly longer than the fixed-dosing schedule (mean DoT [SD]: 14.7 [3.4] and 29.6 [6.7] months, respectively) over a median follow-up of 20.0 and 35.3 months, respectively.

Conclusion: While the median DoT was approximately 12 months for patients treated with V+O and 24 months for patients treated with V+R in the 1L and R/R settings, respectively, more than 50% of patients in both cohorts either discontinued treatment sooner or continued to receive treatment beyond the approved fixed-dosing schedule. For patients treated for less than the fixed-dosing schedules, the mean DoT was < 5 months in those treated with V+O and < 7 months in those treated with V+R. Patients treated beyond the fixed-dosing schedules continued treatment for approximately 3 more months with V+O and 6 more months with V+R. This study provides evidence that a V-based approach may not be suitable for all patients with CLL/SLL. Future studies should include additional follow-up with a larger sample, reasons for treatment discontinuation, and patient molecular genetic profile.