This website is for UK Healthcare Professionals only

*Remission is based on CR, ORR and PR. CR is defined in the SmPC as complete remission.
UK-VNCCLL-220184 | May 2022

Now could be the time for your first-line patients to experience remission powered by V1-3

In the CLL-14 trial the primary endpoint of investigator-assessed PFS was met showing VEN+O superiority vs Clb+O (HR 0.35; 95% CI, 0.23–0.53; P<0.001).3

VENCLYXTO+O is the only fixed treatment duration chemo-free therapy that
can offer your first-line CLL patients:

Complete remission (CR)*

The primary endpoint of investigator-assessed PFS was met showing VEN+O superiority vs Clb+O (HR 0.35; 95% CI, 0.23–0.53 ; P<0.001)3

Rate of INV-assessed CR* 3 months after completing treatment (ITT population; secondary endpoint)3

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).

 

Sustained survival off treatment at 5 years

VEN+O gives the opportunity for sustained survival without continuous treatment in first-line CLL patients1,4

INV-assessed PFS of VEN+O vs Clb+O at 5 years4*

Adapted from Al-Sawaf O et al. 2022.
*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)3.
Median follow-up 65.4 months.
Not tested for statistical significance.

 

Overall survival at 5 years in the ITT population  (secondary endpoint) - 4 years after completing VEN+O4

 

Adapted from Al-Sawaf O et al 2022.
*Median follow-up 65.4 months.
Not tested for statistical significance.

 

Time to next treatment* for VEN+O vs Clb+O over 5 years5

 

Adapted from Al-Sawaf O et al 2022.
*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.6
Median follow-up 65.4 months.
Not tested for statistical significance.

Give your first-line CLL patients a chance to take back their life with a fixed treatment duration1,3,4,7

The safety profile of VENCLYXTO has been evaluated in 758 patients with CLL across 5 clinical trials (one phase I (M12-715), two phase II (M13-982 and M14-032) & two Phase III (MURANO & CLL-14) with VEN-mono, VEN+R or as VEN+O1

*Includes neutropenia and decreased neutrophil count

Neutropenia & infections:1

  • Grade 3 or 4 neutropenia has been reported in patients treated with VENCLYXTO. Complete blood counts should be monitored throughout the treatment period. Dose interruptions or reductions are recommended for patients with severe neutropenia.
  • Serious infections, including sepsis with fatal outcome, have been reported. Monitoring of any signs and symptoms of infection is required. Suspected infections are to receive prompt treatment, including antimicrobials and dose interruption or reduction, and use of growth factors as appropriate.

Dose titration and prophylactic measures effectively mitigated the risk of TLS

Incidence of TLS in patients receiving mitigation measures alongside VENCLYXTO:2,3

*All events were laboratory TLS, (which is defined as the presence of ≥2 events of hyperkalemia, hyperphosphatemia or hypocalcaemia within 24 hours of each other); and occurring in patients who have lymph node(s) ≥5cm or ALC≥25x109/L. Clinical TLS was defined as laboratory TLS event accompanied by increased creatinine/acute renal failure, cardiac dysrhythmia, seizures or death

CLL-14 study design

A Phase III open-label randomised study which evaluated the efficacy and safety of VENCLYXTO + obinutuzumab vs chlorambucil + obinutuzumab in patients with previously untreated CLL and comorbidities3*

*CLL-14 was a multicentre, open-label, Phase III trial. Treatment completed after twelve 28-day cycles.
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 International Workshop for Chronic Lymphocytic Leukaemia (IwCLL) updated National Cancer Institute-sponsored Working Group (NCI-WG) guidelines (2008).
**MRD negativity was assessed at the end of treatment. uMRD = <1 tumour cell per 104 white cells.

 

CLL-13 study design

A Phase III multicentre, open-label study which evaluated the efficacy and safety of VENCLYXTO + obinutuzumab vs CIT (FCR or BR) in treatment-naïve, fit patients.8,9

The CLL-13 trial included 2 other arms which cannot be discussed as they are unlicensed in the UK

MRD negativity was assessed at the end of treatment. uMRD = <1 tumour cell per 104 white cells.
*VENCLYXTO 400 mg daily after initial dose-titration period.
Obinutuzumab dosing: 1000 mg on days 1, 8 and 15 and day 1 of cycles 2-6.
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.
MRD negativity was assessed at the end of treatment. uMRD = <1 tumour cell per 104 white cells.
##Assessed using the International Workshop for Chronic Lymphocytic Leukaemia (IwCLL) updated National Cancer Institute-sponsored Working Group (NCI-WG) guidelines (2008).


VEN+O gives fit first-line patients the opportunity to achieve MRD negativity8*

MRD negativity 3 months after completing treatment: VEN+O vs CIT (FCR/BR) (co-primary endpoint)8*

First data cut-off February 2021.
Median observation time was 27.9 months.
*MRD negativity was assessed at the end of treatment. uMRD = <1 tumour cell per 104 white cells.

 


Significantly higher ORR and CR rate at month 15 vs CIT (FCR/BR)8*†

Rate of INV-assessed CR* 3 months after completing treatment (ITT population; secondary endpoint)8*

First data cut-off February 2021.
Median observation time was 27.9 months.
*Complete response rate is CR+CRi (secondary endpoint).
ORR=CR+CRi+PR (secondary endpoint).


VEN+O demonstrated significantly higher PFS vs CIT (FCR/BR) at 3 years9*

INV-assessed PFS of VEN+O vs CIT (ITT population; secondary endpoint)9*

Adapted from Eichhorst B et al 2022.
Data cut-off February 2022.
*Median observation time was 38.8 months

CLL-13 Adverse events11

Severe AEs (≥CTC Grade 3) occuring in ≥5% of patients in at least one arm and of interest 

Secondary primary malignancy and Richter transformation

For full VENCLYXTO safety information, please refer to the SmPC

Adapted from Eichhorst B et al. 2022.
*Defined by Cairo-Bishop criteria.
Second primary malignancies counted as events not as patients affected.

 

1L = First line; ADR = Adverse drug reaction; AE = Adverse event; ALC = Absolute lymphocyte count; BM Bone marrow; BR = Bendamustine, rituximab; Clb+O = Chlorambucil + obinutuzumab; CIRS = Cumulative illness rating scale; CIT = Chemoimmunotherapy; CLL = Chronic lymphocytic leukaemia; CR = Complete response; CRi = CR with incomplete haematologic recovery; CRR = Complete response rate; CrCl = Creatine clearance; CTC = Common toxicity criteria; FCR = Fludarabine, cyclophosphamide, rituximab; HR = Hazard ratio; INV = Investigator; IRC = Independent review committee; ITT = Intent-to-treat; IV = Intravenous; MRD = Minimal residual disease; NLT = Next anti-leukaemic therapy; ORR = Overall response rate; OS = Overall survival; PB = Peripheral blood; PD = Disease progression; PFS = Progression-free survival; PR = Partial response; SmPC = Summary of product characteristics; TLS = Tumour lysis syndrome; TTnT = Time to next treatment; TP53 = Tumour protein 53; uMRD = Undetectable minimal residual disease; VEN+O = VENCLYXTO + obinutuzumab; VEN+R = VENCLYXTO + rituximab.

References

  1. VENCLYXTO Summary of Product Characteristics.
  2. Seymour JF et al. N Engl J Med. 2018; 378(12): 1107–20.
  3. Fischer K et al. N Engl J Med. 2019; 380: 2225–36.
  4. Al-Sawaf O et al. EHA 2022 Abstract S148.
  5. Al-Sawaf O et al. EHA 2022 Oral presentation. Abstract S148.
  6. Al-Sawaf O et al. Lancet Oncol. 2020; 21(9): 1188–200 (suppl appendix).
  7. Leukaemia Care Living with Leukaemia 2018 Report Available from: https://media.leukaemiacare.org.uk/wp-content/uploads/Living-with-Leukaemia-2018-Full-Report-Web-Version.pdf (accessed July 2022).
  8. Eichhorst B et al. ASH 2021; Oral presentation. Available from: https://ash.confex.com/ash/2021/webprogram/Paper146161.html (accessed July 2022).
  9. Eichhorst B et al. EHA 2022. EHA-4249.
  10. ClinicalTrials.gov NCT02950051. Available from: https://clinicaltrials.gov/ct2/show/NCT02950051 (accessed July 2022).
  11. Eichhorst B et al. EHA 2022. Oral presentation. EHA-4249.

 

Adverse events should be reported. Reporting forms and information can be found at yellowcard.mhra.gov.uk.

Adverse events should also be reported to AbbVie on GBPV@abbvie.com

UK-VNCCLL-220336. Date of preparation: July 2022.