Venetoclax retreatment of real-world patients with chronic lymphocytic leukemia previously treated with venetoclax-based regimens Free

Venetoclax (Ven) has notable therapeutic potential in the treatment of chronic lymphocytic leukemia (CLL). As a result of the CLL14 and MURANO trials, Ven is approved as a fixed duration treatment in frontline (1L) with obinutuzumab (VenO) for 12 months (mo) and in relapsed/refractory with rituximab (VenR) for 24 mo. More CLL patients (pts) will require treatment following a period of remission after prior fixed-duration with Ven. To optimize sequencing of CLL therapies, it is important to better understand the effectiveness of Ven retreatment. A previous multicenter retrospective study found supportive results for the clinical practice of Ven retreatment among CLL pts. Given that over half of the pts were from clinical trials, our study builds on this research by investigating Ven retreatment in a large cohort of pts treated outside of clinical trials.

This retrospective observational study utilized the Optum Market Clarity database to identify pts retreated with Ven between 4/11/2016 to 9/30/2024. Our cohort included CLL pts who were treated with a Ven-based regimen (Ven1) and received a second Ven-based regimen (Ven2; index date) in a later line of therapy (LOT). Pts were included if they were ≥18 years old with a CLL/SLL diagnosis, received Ven starter pack (SP) and one non-SP claim of Ven within 90 days after Ven1, had evidence of retreatment with Ven defined as receipt of Ven SP after >90 consecutive days without treatment. Pts had continuous medical and pharmacy benefits or EHR activity for ≥2 years prior to Ven1, with ≥30 days of follow-up after initiating Ven2. Pts with Acute Myeloid Leukemia (AML) and clinical trial participation prior to Ven1 and Ven2 were excluded. The study assessed patient characteristics, treatment patterns, and outcomes of Ven2.

Ven2 outcomes were Time to Next Treatment or Death (TTNTD) and the Time to Treatment Discontinuation (TTD). TTNTD was the period between Ven2 initiation and the next line of therapy or death, while TTD was the time from Ven2 initiation to discontinuation, determined by >90-day gap or death. The median time and 12- and 18-month probability of each event were estimated by the Kaplan-Meier (KM) method. Two subgroup analyses assessed TTNTD in pts who received (1) VenO/R in Ven2 (2) consecutive Ven treatment in 1→2L or 2→3L. Analyses were descriptive.

Our study included 48 Ven retreated pts, with a median age at Ven2 of 67.0 years and 97.9% receiving Ven2 in 2019 or later. Of the 48 pts, 70.8% were males, 85.4% White, with a majority on Medicare (62.5%) or commercial insurance (29.2%). Median Charlson Comorbidity Index score was 3.0 (IQR: 2.0-5.0), and median duration from first CLL treatment to Ven1 of 41.0 months (IQR: 24.5-60.0).

The median time between end of Ven1 and start of Ven2 was 21.2 mo (IQR: 9.4-32.1). Most pts (85.4%) had no therapy between Ven1 and Ven2. The median Ven1 duration was 12.1 mo (IQR: 4.1-24) and median LOT prior to Ven1 was 1 (IQR: 1-2). A majority of patients (68.8%) received Bruton's tyrosine kinase inhibitor (BTKi) before Ven1. Additionally, 8.3% of pts received Ven1 as first-line treatment. Ven was prescribed as monotherapy (58.3%) in Ven1 followed by VenO/R (33.3%) and Ven+BTKi-based (8.4%). Median LOT before Ven2 was 2 (IQR: 2-3). Ven2 regimens included monotherapy (58.3%), VenO/R (27.1%) and Ven+BTKi-based (12.6%).

With a median follow-up time from Ven2 initiation of 11.1 mo (IQR: 6.0-22.7), the median TTNTD (mTTNTD) for Ven2 was 25.9 mo with 12- and 18-mo KM rates of 61.2% and 57.3%, respectively. For pts treated with VenO/R as Ven2, mTTNTD was not reached (NR); 12- and 18-mo rates were 75.0%. For pts with consecutive Ven treatment, mTTNTD for Ven2 was 25.9 mo; 12- and 18-mo rates were 57.4%. The median TTD for Ven2 was 9.3 mo (IQR: 6.1-25.4) with 12- and 18-mo KM rate of 43.0% and 39.1%, respectively.

We report on the largest cohort of CLL pts retreated with Ven. The mTTNTD for Ven2 was 26 mo, indicating that retreatment with Ven is a viable treatment strategy. Additionally, when using VenO/R for retreatment, the mTTNTD was NR, demonstrating durability of this strategy. Taken together, retreatment with Ven may be considered to optimize patient outcomes. Continued research is necessary to further clarify the effectiveness of Ven retreatment with longer follow-up and through prospective studies (i.e. ReVenG), particularly for pts receiving a fixed-duration Ven regimen as initial CLL therapy.