Note to affiliates: This update to the venetoclax CLL AbbVie Pro site includes a homepage headline, updated CLL14 6-year and MURANO 7-year data sets, and other streamlined content updates. The CLL14 6-year and MURANO 7-year data have been updated based on the EHA 2023 abstracts. For countries that cannot use these data sets, please follow local regulations and MRLO guidance, and revert to CLL14 5-year and MURANO 5-year published data from the product label.
Primary analysis in ITT population for VEN+O vs O+Clb1:
INV-assessed PFS†: Reduced risk of progression or death (HR=0.35; 95% CI: 0.23–0.53 [P<0.0001]).
| • | Median follow-up of 28 months |
Additional analyses:
6-year PFS estimate (INV-assessed)2‡: 53% vs 22% (HR=0.40; 95% CI: 0.31–0.52) after 5 years off treatment.
| • | Median PFS of 76.2 months with VEN+O vs 36.4 months with O+Clb |
INV-assessed complete remission (CR/CRi)1: 50% vs 23% (P<0.0001).
| • | ORR: 85% (95% CI: 79.2–89.2) vs 71% (95% CI: 64.8–77.2 [P=0.0007]) |
Primary analysis in ITT population for VEN+R vs BR:
INV-assessed PFS†: Reduced risk of progression or death (HR=0.17; 95% CI: 0.11–0.25 [P<0.0001]).
| • | Median follow-up of 23.8 months |
Additional analyses:
7-year PFS estimate (INV-assessed)3‡: 23% (95% CI: 16.1–29.9) vs NE after ~5 years off treatment.
| • | Median PFS of 54.7 months with VEN+R (95% CI: 52.3–59.9) vs 17.0 months with BR (95% CI: 15.5–21.7) |
INV-assessed complete remission (CR/CRi)1‡: 27% vs 8%.
| • | ORR: 93% (95% CI: 88.8–96.4) vs 68% (95% CI: 60.6–74.2) |
*See full dosing information for VEN+O and for VEN+R in the dosing and administration section.
†Primary endpoint.
‡Results are descriptive only.
1L=first line; CLL=chronic lymphocytic leukaemia; VEN+O=VENCLYXTO + obinutuzumab; ITT=intent to treat; O+Clb=obinutuzumab + chlorambucil; INV=investigator; PFS=progression-free survival; HR=hazard ratio; CI=confidence interval; CR=complete remission; CRi=complete remission with incomplete bone marrow recovery; ORR=overall response rate; 2L+=second line + later lines of therapy; VEN+R=VENCLYXTO + rituximab; BR=bendamustine + rituximab; NE=not evaluable.
2L+ CLL: VENCLYXTO + RITUXIMAB
test
MURANO TRIAL WAS DESIGNED TO ALLOW PATIENTS TO COMPLETE VENCLYXTO + RITUXIMAB TREATMENT IN 2 YEARS1*
MURANO evaluated VENCLYXTO + rituximab vs a standard CIT regimen (bendamustine + rituximab)
*MURANO was a multicentre, randomised, open-label, phase 3 trial. Treatment complete after 5-week dose-titration period and twenty-four 28-day cycles.
†VENCLYXTO 400 mg daily after initial dose-titration period in the absence of disease progression or unacceptable toxicity.
‡Rituximab dosing: 375 mg/m2 IV Day 1, Cycle 1 (initiated after the 5-week dose titration schedule); 500 mg/m2 IV Cycles 2–6. Each cycle was 28 days.
§Bendamustine dosing: 70 mg/m2 IV Days 1 and 2, Cycles 1–6. Each cycle was 28 days.
||Venetoclax is taken for 24 months starting Day 1, Cycle 1 of rituximab.
Click here for titration protocols and full dosing information.
Select inclusion criteria4
| • | Previously treated with 1 to 3 prior therapies (including at least 1 chemotherapy-containing regimen) |
| • | Patients treated with prior bendamustine, provided the duration of response was ≥2 years |
Primary endpoint1
| • | INV-assessed PFS¶ |
Select secondary endpoints
| • | IRC-assessed PFS |
| • | INV- and IRC-assessed ORR,# CR/CRi, nPR, and PR |
| • | Overall survival (OS) |
| • | TTNT |
| • | uMRD rates at EoCT** |
Primary analysis and results (ITT population)
Median follow-up of 23.8 months. Median PFS was not reached with VEN+R vs 17 months (95% CI: 15.5–21.6) with BR in the primary analysis.
| • | 2-year PFS estimate: 85% (95% CI: 79.1–90.6) with VEN+R vs 36% (95% CI: 28.5–44.0) with BR (HR=0.17; 95% CI: 0.11–0.25 [P<0.0001]) |
¶Assessed using the iwCLL updated NCI-WG guidelines (2008).
#ORR=CR/CRi+nPR+PR.
**MRD was evaluated in the PB and/or bone marrow using ASO-PCR and/or flow cytometry. The cutoff for an undetectable (negative) status was <1 CLL cell per 104 leukocytes.
CIT=chemoimmunotherapy; IV=intravenous; IRC= independent review committee; nPR=nodular partial remission; TTNT=time to next anti-leukaemic treatment; EoCT=end of combination treatment; iwCCL=International Workshop on chronic Lymphocytic Leukemia; NCI-WG=National Cancer Institute--sponsored Working Group; PB=peripheral blood; ASO-PCR=allele-specific oligonucleotide polymerase chain reaction.
VENCLYXTO + RITUXIMAB INDUCED DEEP RESPONSES,* INCLUDING HIGH RATES OF uMRD,† IN PERIPHERAL BLOOD1
Unparalleled rates of uMRD at EoCT for VEN+R vs BR in 2L+ CLL
IN PERIPHERAL BLOOD
| • | In evaluable patients who completed 2 years of VEN+R treatment without progression, the rate of uMRD in PB at EoT was 64% in the VEN+R arm5,6 |
| • | Rates of uMRD in bone marrow at the EoCT were 16% (95% CI: 10.7–21.3) in the VEN+R arm and 1% (95% CI: 0.1–3.7) in the BR arm1 |
More than 3x as many patients achieved complete remission with VEN+R (27%) vs BR (8%)‡
COMPLETE REMISSION (CR/CRi) RATE
| • | INV-assessed ORR was 93% (95% CI: 88.8–96.4) in the VEN+R arm vs 68% (95% CI: 60.6–74.2) in the BR arm |
*Deep response as measured by uMRD or CR.
†uMRD (secondary endpoint) results in ITT population are presented. Results are descriptive. The cutoff for an undetectable (negative) status was <1 CLL cell per 104 leukocytes.
‡Results are descriptive.
EoT=end of treatment.
Note to affiliates: This page contains MURANO 5-year PFS data from the October 2022 EU SmPC, as well as 7-year follow-up results from an abstract presented by Kater et al at EHA 2023.
PFS FOR VENCLYXTO + RITUXIMAB PATIENTS: RESULTS AT 5 AND 7 YEARS1,3
Results of a 5-year analysis1*
Longer-lasting PFS: 54 months mPFS for VEN+R vs 17 months for BR (HR=0.19; 95% CI: 0.15–0.26).
INV-ASSESSED PFS IN THE ITT POPULATION
Results of a 7-year analysis3*
mPFS for VEN+R was 55 months (95% CI: 52.3–59.9) vs 17 months (95% CI: 15.5–21.7) for BR (HR=0.25).
PFS benefit was sustained in patients off treatment for ~5 years1,3
*Results are descriptive.
mPFS=median progression-free survival; PD=progressive disease.
See MURANO study design section for primary analysis data.
Note to affiliates: This page contains data taken from the October 2022 EU SmPC and published by Seymour et al in Blood in a 2022 article and its supplementary appendix, as well as 7-year follow-up results from an abstract presented by Kater et al at EHA 2023.
TIME TO NEXT TREATMENT FOR VENCLYXTO + RITUXIMAB PATIENTS: RESULTS AT 5 AND 7 YEARS3,7,8
Results of a 5-year analysis7,8*
HR=0.26 (95% CI: 0.20—0.35).
Time off CLL treatment was sustained for more than 3 years in over half of 2L+ patients who received VEN+R
MEDIAN TIME TO NEXT CLL TREATMENT
*Results are descriptive.
mTTNT=median time to next anti-leukaemic treatment.
NE-not evaluable.
Note to affiliates: These data are taken from the October 2022 EU SmPC.
VENCLYXTO + RITUXIMAB PFS BENEFIT WAS CONSISTENT ACROSS SUBGROUPS, INCLUDING HIGH-RISK PATIENTS1*†
INV-ASSESSED PFS SUBGROUP 5-YEAR ANALYSIS
Data cutoff: 8 May 2020.
PFS benefits in these high‑risk subgroups were sustained
beyond the 2 years of VEN+R treatment
*High-risk subgroups include del(17p), TP53 deletion and/or mutation present, as well as IGHV unmutated.
†Results are descriptive.
‡Unstratified hazard ratio is displayed on the x-axis with logarithmic scale.
Del=deletion;
TP53=tumour protein p53; IGHV=immunoglobulin heavy-chain variable gene.
See SmPC for additional PFS subgroups analyses.
Note to affiliates: This page contains MURANO 5-year OS data from the October 2022 EU SmPC, as well as 7-year follow-up results from an abstract presented by Kater et al at EHA 2023.
OS FOR VENCLYXTO + RITUXIMAB PATIENTS: RESULTS AT 5 AND 7 YEARS1,3
In the primary OS analysis (ITT population; median follow-up 23.8 months), the HR for VEN+R vs BR was 0.48 (95% CI: 0.25–0.90). Median OS was not reached for either treatment group.
Results of a 5-year analysis1*
HR=0.40 (95% CI: 0.26–0.62). Median OS was not reached for either treatment group.
UPDATED 5-YEAR ANALYSIS: OS IN THE ITT POPULATION*
Results of a 7-year analysis3*
OS rates were 70% for VEN+R (95% CI: 62.8–76.5) vs 51% for BR (95% CI: 43.3–58.7) (HR=0.53).
*Results are descriptive.
Note to affiliates: These data are taken from an abstract presented by Kater et al at EHA 2023.
RESULTS IN VEN+R PATIENTS WHO RECEIVED SUBSEQUENT VEN+R TREATMENT3*
| • | 25 patients received VEN+R re-treatment after a median treatment-free interval of 2.3 (1.2–3.1) years |
| • | Among these patients median PFS was 23.3 months (95% CI: 15.6–24.3) |
ORR RESULTS IN THIS FOLLOW-UP ANALYSIS3
Median follow-up time: 33.4 months
*Results are descriptive.
Best ORR=CR/CRi+PR/nPR.
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References: 1. VENCLYXTO Summary of Product Characteristics. Ludwigshafen, Germany: AbbVie Deutschland GmbH & Co. KG. 2. AI-Sawaf O, Robrecht S, Zhang C, et al. Venetoclax-obinutuzumab for previously untreated chronic lymphocytic leukemia: 6-year results of the randomized CLL14 study. HemaSphere. 2023;7(S3):1-3. 3. Kater A, Harrup R, Kipps TJ, et al. Final 7-year follow up and retreatment substudy analysis of MURANO: venetoclax-rituximab (VENR)-treated patients with relapsed/refractory chronic lymphocytic leukemia (R/R CLL). Abstract presented at the European Hematology Association Congress 2023; June 8-11, 2023; Frankfurt, Germany. 4. Seymour JF, Kipps TJ, Eichhorst B, et al. Venetoclax-rituximab in relapsed or refractory chronic lymphocytic leukemia. N Engl J Med. 2018;378(12):1107-1120. 5. Kater AP, Wu JQ, Kipps T, et al. Venetoclax plus rituximab in relapsed chronic lymphocytic leukemia: 4-year results and evaluation of impact of genomic complexity and gene mutations from the MURANO phase III study. J Clin Oncol. 2020;38(34):4042-4054. 6. Kater AP, Wu JQ, Kipps T, et al. Venetoclax plus rituximab in relapsed chronic lymphocytic leukemia: 4-year results and evaluation of impact of genomic complexity and gene mutations from the MURANO phase III study. J Clin Oncol. 2020;38(34):4042-4054(suppl). 7. Seymour JF, Kipps TJ, Eichhorst BF, et al. Enduring undetectable MRD and updated outcomes in relapsed/refractory CLL after fixed-duration venetoclax-rituximab. Blood. 2022;140(8):839-850. 8. Seymour JF, Kipps TJ, Eichhorst BF, et al. Enduring undetectable MRD and updated outcomes in relapsed/refractory CLL after fixed-duration venetoclax-rituximab. Blood. 2022;140(8):839-850(suppl).
ALL-VNCCLL-220060 May 2024