Efficacy and Safety of Treatment Venetoclax Monotherapy or Combined with Rituximab in Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL) in the Real-World Setting in Spain: An Update of the Venares Study

Abstract

Introduction: The VENARES study confirmed that venetoclax in monotherapy (VenM) or combined with rituximab (VenR) was effective in heavily pretreated CLL patients (pts) (ORR at 9 months: 84.3%); and safety was consistent with prior experiences. Here we present an additional analysis of efficacy and safety comparing subgroups. Methods: This is non-interventional retrospective, multicenter, post-marketing, observational study where data from adult CLL pts treated with Ven at least 9 months before were included. According to local label, pts were eligible for VenM, treatment continued until disease progression or no longer tolerated, or VenR treatment, venetoclax administered for up to 2 years plus rituximab for the first 6 months. Pts were reviewed until the date of last follow-up or death. Results: One hundred and twenty-four out of 125 eligible pts were finally assessed for efficacy. VenM in 80 pts (64.5%) and VenR in 36 pts (29%). Ven with obinutuzumab in 5 pts (4%) and with other drugs in 3 pts (2.4%). Patient characteristics by subgroup are summarized in Table 1. Eighty-three of 125 pts were evaluable for the primary objective: overall response rate (ORR) at 9 mo was 84.3% (70 pts): CR/CRi in 44 (53%) and PR/nPR in 26 pts (31.3%). By subgroups, ORR at 9 mo was 80.4% (41 of 51 pts) in VenM pts, with 47% of CR/CRi, and 33.3% PR/nPR; and 92.3.% (24 of 26 pts) in VenR pts, with 61.5% CR/CRi, and 30.8% PR/nPR. ORR at 9 mo were 81% for prior bruton tyrosine kinase (BTKi) treated VenM pts and 78.6% for BTKi naïve VenM pts; and 93.3% for prior BTKi VenR pts and 90.9% for BTKi naïve VenR pts (Table 2). Sixty-four of 83 evaluable pts had reached 400 mg of Ven. ORR at 9 mo were 85.94% in pts who had received 400 mg and 78.95% in the rest. In VenM pts, ORR at 9 mo were 80% for 400 mg and 81.3% for the rest. In VenR pts, ORR at 9 mo was 92% for 400 mg, all but one pts reached the full dose. The median PFS was not reached at the time of the analysis (18-May-2022) in either subgroup. In VenM pts, PFS at 18 mo was 78.7% (95% CI, 67.4- 86.5) and at 24 mo 72.7% (95% CI, 55.3-84.2). In VenR pts, PFS at 18 mo was 89.1% (95% CI, 57.9- 97.6) and not able to be estimated at 24 mo. In assessed pts, best undetectable MRD was reached in 13 pts (43.3%). uMRD was more common in VenR pts (83.3%, 5 of 6 pts) than in VenM (33.3%, 8 of 24 pts). Sixty-seven pts (53.6%) experienced at least 1 specific AE and 14 pts at least 1 specific SAE both related to Ven. In 34 pts, the treatment was withdrawn, 13 of which were due to AE, all of them in the VenM subgroup. Forty-four of 80 pts (55%) and 17 of 36 (47.2%) pts in VenM and VenR subgroups reported at least 1 specific AE related to Ven. 22 pts (27.5%) and 7 pts (19.4%) had neutropenia G3/4 in VenM and VenR, respectively. 6 pts (7.5%) and 3 (8.3%) had febrile neutropenia in VenM and VenR. Seven pts (8.75%) and 0 pts had a serious infection in VenM and VenR. 3 pts (3.75%) and 1(2.78%) had a TLS event in VenM and VenR; there was only 1 pt with clinical TLS non-related to Ven in the VenM subgroup. Two (2.5%) and 0 pts presented a Richter transformation in VenM and VenR, respectively. In pts with known TLS risk during Ven ramp-up, hospitalized pts were: 20% (8/40) with high risk, 62.5% (25/40) medium and 17.5% (7/40) low risk in VenM. In VenR subgroup, 6.2% (1/16) with high risk, 62.5% (10/16) medium and 31.3% (5/16) low risk. Conclusions: Updated subgroup analysis showed that treated pts with VenR fixed treatment duration achieved higher clinical responses compared to VenM (ORR at 9 mo 92.3% vs 80%) however VenR pts had been less heavily pretreated. ORR at 9 mo was maintained in both BTKi exposed and BTKi naïve pts in the two subgroups, and BTKi naïve pts had a higher percentage of CR/CRi compared to BTKi exposed pts, especially in VenR subgroup. Pts that achieved full dose of Ven (400mg) achieved higher clinical responses. No new safety events were detected. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal