This promotional website is for UK Healthcare Professionals involved in the management of haematological malignancies. Adverse event reporting information can be found below.
VENCLYXTO + obinutuzumab in 1st line CLL
VENCLYXTO + obinutuzumab (VEN+O) vs chlorambucil + obinutuzumab (Clb+O)1,2*
*CLL-14 was a multicentre, open-label, Phase III trial to compare the efficacy and safety of VEN+O Versus Clb+O in previously untreated CLL patients with coexisting medical conditions. Treatment was completed after twelve 28-day cycles.
†VENCLYXTO was started on Cycle 1, Day 22 and increased to full dose for Cycle 3, Day 1. VENCLYXTO was continued until the end of Cycle 12. VENCLYXTO 400 mg daily after initial dose-titration period.
‡Obinutuzumab dosing: 100 mg Cycle 1, Day 1, followed by 900 mg on Days 1 or 2; 1000 mg on Days 8 and 15 and Day 1 of subsequent cycles.
§Chlorambucil dosing: 0.5 mg/kg on Days 1 and 15 of each 28-day cycle.
¶Assessed using the iwCLL updated NCI-WG guidelines (2008).
**MRD negativity was assessed at the end of treatment. MRD negativity = <1 tumour cell per 104 white cells.
Over twice as many VEN+O patients remained progression-free vs Clb+O 6 years after initiating VEN+O treatment
PFS (INV-assessed) of VEN+O vs Clb+O at 6 years3* (primary endpoint)
Adapted from Al-Sawaf O et al. 2023.
*In the primary analysis at 28.1 months in the ITT population, PFS with VEN+O was superior to Clb+O (HR: 0.35; 95% CI: 0.23–0.53; P<0.001)1
†Median follow-up 76.4 months.
‡Not tested for statistical significance.
The majority of VEN+O patients remained treatment-free 6 years after initiating treatment
Time to next treatment* for VEN+O vs Clb+O over 6 years (secondary endpoint)3
Adapted from Al-Sawaf O et al. 2023.
*TTnT was defined as the time between the date of randomisation to the date of first intake of new anti-CLL treatment or death prior to initiating new anti-CLL treatment.
†Median follow-up 76.4 months.
‡Not tested for statistical significance.
Over 75% overall survival for VEN+O patients 6 years after initiating treatment
6-year-overall survival rate of VEN+O vs CIT (ITT population; secondary endpoint)3
Adapted from Al-Sawaf O et al. 2023.
*Median follow-up 76.4 months.
†Not tested for statistical significance.
Rate of INV-assessed CR* 3 months after completing treatment (ITT population; secondary endpoint)1
Complete remission (CR+CRi) rate1
Median follow-up time in the primary analysis was 28 months (range: 0-36 months).
*Remission is based on CR and ORR. CR is defined in the SmPC as complete remission.
†ORR=CR+CRi+PR (secondary endpoint).
Most frequent ≥Grade 3 adverse events during and after treatment across both treatment arms.
Al-Sawaf O et al. 2023.3
Median follow-up 76.4 months.
CI, Confidence Interval; CIRS, Cumulative illness rating scale; CIT, Chemoimmunotherapy; Clb+O, Chlorambucil and Obinutuzumab; CLL, Chronic lymphocytic leukaemia; CrCl, Creatine clearance; CR, Complete response; CRi, CR with incomplete marrow recovery; HR, Hazard ratio; IRC, Independent review committee; INV, Investigator; ITT, Intent-to-treat; IV, Intravenous; iwCLL, International workshop for CLL; MRD, Minimal residual disease; NCI-WG, National Cancer Institute-sponsored working group; NLT, Next anti-leukaemic therapy; ORR, Overall response rate; PB, Peripheral blood; PD, Disease progression; PFS, Progression-free survival; PR, Partial response; TTnT, Time to next treatment; VEN+O, VENCLYXTO + Obinutuzumab; 1L, First line.
References
- Fischer K et al. N Engl J Med. 2019; 380: 2225-36.
- VENCLYXTO Summary of Product Characteristics.
- AI-Sawaf O et al. Abstract S145. EHA Congress. 2023.
- Eichhorst B et al. N Engl J Med. 2023; 388: 1739-54.
UK-VNCCLL-230495. Date of preparation: April 2024.
VENCLYXTO + obinutuzumab (VEN+O) vs CIT (FCR or BR) arms4*
*CLL-13 was a multicentre, open-label, Phase III, multiple arm study for first-line treatment of fit CLL patients. The study evaluated whether standard chemoimmunotherapy (FCR, BR) in frontline treatment of physically fit CLL patients can be replaced by combinations of targeted drugs (VENCLYXTO) with anti-CD20-antibodies (obinutuzumab). The CLL-13 trial included two other arms which cannot be discussed as they are unlicensed in the UK.
Co-primary endpoints were both met at primary analysis (median follow-up 38.8 months)
#MRD negativity was assessed at the end of treatment.
†VENCLYXTO was started on Cycle 1, Day 22 and increased to full dose for Cycle 3, Day 1. VENCLYXTO was continued until the end of Cycle 12. VENCLYXTO 400 mg daily after initial dose-titration period.
‡Obinutuzumab dosing: 100 mg Cycle 1, Day 1, followed by 900 mg on Days 1 or 2; 1000 mg on Days 8 and 15 and Day 1 of subsequent cycles.
§FCR for patients ≤65 years: fludarabine 25 mg/m2 days 1-3, cyclophosphamide 250 mg/m2 days 1-3, rituximab 375 mg/m2 day 1 cycle 1 and 500 mg/m2 day 1 cycles 2-6.
¶BR for patients >65 years: bendamustine 90 mg/m2 day 1-2 of cycles 1-6, rituximab 375 mg/m2 day 1 cycle 1 and 500 mg/m2 day 1 cycles 2-6. Each cycle was 28 days.
**Assessed using the iwCLL updated NCI-WG guidelines (2008).
VEN+O demonstrated significantly higher PFS vs CIT (FCR/BR) 4 years after initiating VEN+O treatment
PFS of VEN+O vs CIT* (ITT population; secondary endpoint in the Phase 3 GAIA/CLL-13 Trial)5
- Median PFS:2
VEN+O: not reached
CIT: 59.4 months - Co-primary endpoint of PFS between relevant arms was met at the primary analysis after median follow-up 38.8 months. At the primary analysis, the secondary endpoint of PFS between VEN+O and CIT was also met (p<0.001).4
Adapted from Furstenau, M 2023.
*The CLL-13 trial included other arms, which cannot be discussed as they are unlicensed in the UK.
†After a median observation time of 50.7 months (interquartile range 44.6-57.9), all pts are now off study treatment.
At 4 years 90% of VEN+O patients were without a new treatment vs 77% for CIT patients
Time to next treatment for VEN+O vs CIT over 4 years (secondary endpoint)5
Adapted from Fürstenau M et al. 2023.
Data cutoff January 2023.
*Median observation time was 50.7 months.
Rate of INV-assessed CR* 3 months after completing treatment (ITT population; secondary endpoint)4†
Complete response (CR+CRi) rate*
Co-primary endpoint of uMRD between VEN+O and CIT arms was met:
At month 15, a significantly higher percentage of patients in the VEN+O arm had uMRD compared to the CIT arm (86.5% [97.5% CI 80.6 91.1] vs. 52.0% [97.5% CI 44.4-59.5], p<0.001)
Adapted from Eichhorst B et al. 2023.
First data cutoff February 2021.
*Complete response rate is CR+CRi (secondary endpoint).
†Median follow-up 38.8 months.
‡ORR=CR+CRi+PR (secondary endpoint).
Median follow-up: 38.8 months.
*Adverse events reported as single term.
†Adverse event reported as high-level term.
‡Including clinical and laboratory. TLS according to Cairo–Bishop as per protocol; no fatal TLS occurred.
Adapted from Eichhorst B et al. 2023.
AEs, Adverse events; BR, bendamustine–rituximab; CI, Confidence Interval; CIRS, Cumulative illness rating scale; CIT, Chemoimmunotherapy; CLL, Chronic lymphocytic leukaemia; CR, Complete response; CrCl, Creatine clearance; CRi, CR with incomplete marrow recovery; CTC, Common terminology criteria; del(17p), 17p deletion; FCR, fludarabine–cyclophosphamide–rituximab; HR, Hazard ratio; INV, Investigator; ITT, Intent-to-treat; IV, Intravenous; iwCLL, International workshop on CLL; MRD, Minimal residual disease; NCI-WG, National Cancer Institute-sponsored working group; ORR, Overall response rate; PFS, Progression-free survival; PR, Partial response; TLS, Tumour lysis syndrome; TP53, Tumour protein 53; TTnT, Time to next treatment; VEN+O, VENCLYXTO + Obinutuzumab.
References
- Fischer K et al. N Engl J Med. 2019; 380: 2225-36.
- VENCLYXTO Summary of Product Characteristics.
- AI-Sawaf O et al. Abstract S145. EHA Congress. 2023.
- Eichhorst B et al. N Engl J Med. 2023; 388: 1739-54.
- Fürstenau M et al. Oral presentation S642. ASH. 2023.
UK-VNCCLL-230497. Date of preparation: April 2024.
You are advised to read the Prescribing Information and Summary of Product Characteristics to evaluate patient suitability for VENCLYXTO.
VENCLYXTO PRESCRIBING INFORMATION
VENCLYXTO SUMMARY OF PRODUCT CHARACTERISTICS (GB)
VENCLYXTO SUMMARY OF PRODUCT CHARACTERISTICS (NI)
