Efficacy of venetoclax in patients with relapsed/refractory chronic lymphocytic leukaemia: analysis of the international single-arm phase 3b trial VENICE-1

Abstract

Background: most patients with chronic lymphocytic leukaemia (CLL) progress
following (re)treatment with targeted- or chemoimmuno-therapy and have limited subsequent treatment options. Response levels to single-agent venetoclax in the relapsed setting were unknown. This study aimed to assess venetoclax efficacy in Bcell receptor-associated kinase inhibitors (BCRi)-naïve or prior BCRi-treated patients.

Methods: the phase 3b VENICE-I trial (NCT02756611) assessed efficacy and safety of venetoclax monotherapy in adults with relapsed/refractory (R/R) CLL, stratified by previous exposure to a BCRi. Eligible participants were aged ≥18 years with previously treated R/R CLL. Presence of del17p or TP53 aberrations and prior BCRi treatment were permitted. Patients received 5-week ramp-up to 400 mg of oral venetoclax and were treated for ≤108 weeks with 2 years follow-up after discontinuation, or optional extended access. The primary efficacy endpoint was complete remission (CR) rate (CR + CR with incomplete marrow recovery [CRi]) in BCRi-naïve patients. Analyses used the intent-to-treat population.

Findings: this study enrolled 258 patients (first patient first visit June 22, 2016; last patient last visit March 11, 2022 [study completion]) with R/R CLL; 191 were BCRinaïve and 67 were BCRi-experienced. Overall, 70% (180) of patients were male. Median (IQR) follow-up in the overall cohort, and BCRi-naïve and -experienced groups was 49·5 (47·2, 54·1), 49·2 (47·2, 53·2), and 49·7 (47·4, 54·3) months, respectively. Of 191 BCRi-naïve patients, 66 (35%) achieved CR + CRi; 18/67(27%) BCRi-experienced patients achieved CR + CRi. Grade ≥3 TEAEs and SAEs were reported in 79% (n=203/258) and 53% (n=136/258) of patients, respectively. The most common TEAE
and SAE was neutropenia (37%; n=96/258). and pneumonia (8%; n=21/258),
respectively. There were 13 (5%) deaths reported due to AEs. No new safety signals were identified.

Interpretation: these data demonstrate deep and durable responses with venetoclax monotherapy in patients with R/R CLL, including BCRi-experienced patients.

Funding: AbbVie-sponsored study.

More information

Identifiers

ORCID for Francesco Forconi: orcid.org/0000-0002-2211-1831

Catalogue record

Export record