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      • This website is for UK Healthcare Professionals only

      This promotional website is for UK healthcare professionals involved in the care of patients with cancer. Adverse event reporting information can be found below.

      Venclyxto_UK_R_4C
      VENCLYXTO AML PRESCRIBING INFORMATION
      VENCLYXTO GB SUMMARY OF PRODUCT CHARACTERISTICS
      VENCLYXTO NI SUMMARY OF PRODUCT CHARACTERISTICS

      UK-VNCAML-240003  |  April 2024.

      Home

      Efficacy & Safety

      Dosing & TLS prophylaxis
      (tumour lysis syndrome)

      Drug-Drug Interactions

      Cytopenia Management

      FAQs

      References

          

      Initiation

      What is the dose adjustment in patients with renal or hepatic impairment?
      What is the guidance on TLS prophylaxis for AML patients with risk factors for TLS?

      CYP3A inhibitors

      What was the level and duration of CYP3A inhibitor use in VIALE-A?
      What is the dose adjustment of VENCLYXTO in the presence of CYP3A inhibitor?
      Is there any data on use of VENCLYXTO with antifungals other than azoles?
      When stopping CY3PA inhibitors, how is VENCLYXTO dose-titrated from the reduced dose to the full dose?
      Does use of antimicrobial prophylaxis impact patient outcomes with VENCLYXTO?

      Cytopenia

      How is remission defined in VIALE-A and the SmPC?
      How is cytopenia managed prior to and after remission?
      In VIALE-A, what was the incidence of dose interruptions and cycle delays?
      How many patients received a Granulocyte-Colony Stimulating Factor (G-CSF) in the VIALE-A studies?

      Other

      What are the common and serious adverse events reported in VIALE-A?
      Is VENCLYXTO routinely commissioned across the UK?

      UK-VNCAML-240068  |  April 2024. 

      VENCLYXTO in combination with a hypomethylating agent is indicated for the treatment of adult patients with newly diagnosed acute myeloid leukaemia (AML) who are ineligible for intensive chemotherapy.1

      You are advised to read the Prescribing Information and Summary of Product Characteristics (GB SmPC; NI SmPC) to evaluate patient suitability for VENCLYXTO.

      Adverse events should be reported.
      Reporting forms and information can be found at https://yellowcard.mhra.gov.uk or via the MHRA Yellow Card app, available in the Google Play or Apple App Stores. 
      Adverse events should also be reported to AbbVie on GBPV@abbvie.com

      WHAT IS THE DOES ADJUSTMENT IN PATIENTS WITH RENAL OR HEPATIC IMPAIRMENT?

      Renal impairment1

      SEVERITYDOSE MODIFICATIONS
      Mild, moderate or severe

      No dose adjustment is needed for patients with mild, moderate or severe renal impairment (CrCI ≥ 15 mL/min and < 90mL/min).

      Patients with reduced renal function (CrCI < 80mL/min) may require more intensive prophylaxis and monitoring to reduce the risk of TLS at initiation and during the dose-titration phase. 

      VENCLYXTO should be administered to patients with severe renal impairment (CrCI ≥ 15 mL/min and < 30mL/min) only if the benefit outweighs the risk and patients should be monitored closely for signs of toxicity due to increased risk of TLS.

      Hepatic impairment1

      SEVERITYDOSE MODIFICATIONS
      Mild or moderate

      No dose adjustment is recommended in patients with mild or moderate hepatic impairment. 

      Patients with moderate hepatic impairment should be monitored more closely for signs of toxicity at initiation and during the dose-titration phase. 

      SevereA dose reduction of at least 50% throughout treatment is recommended. These patients should be monitored more closely for signs of toxicity. 

       

      Please refer to the SmPC for full safety information

      CrCl=creatinine clearance; TLS=tumour lysis syndrome.

      WHAT IS THE GUIDANCE ON TLS PROPHYLAXIS FOR AML PATIENTS WITH RISK FACTORS FOR TLS??

      Consider additional measures, including increasing laboratory monitoring and reducing VENCLYXTO starting dose for patients with risk factors for TLS, e.g. circulating blasts, high burden of leukaemia involvement in bone marrow, elevated pre-treatment LDH levels, reduced renal function.1

      PRIOR TO INITIATION1

      WBC count <25 x 109/L

      Cytoreduction may be required

      Assess blood chemistries and correct pre-existing abnormalities

      • Potassium 
      • Phosphorus 
      • Calcium 
      • Uric acid 
      • Creatinine

      Administer prophylaxis

      All patients should be adequately hydrated and receive anti-hyperuricaemic agents prior to initiation of VENCLYXTO and throughout the dose titration period

      Monitor blood chemistries for TLS at pre-dose, 6-8 hours after each new dose, and 24 hours after reaching final dose

      More guidance is available in Dose initiation & TLS prophylaxis

      AML=Acute Myeloid Leukaemia; AZA=azacitidine; LDH=lactate dehydrogenase; TLS=tumour lysis syndrome; VEN=VENCLYXTO; WBC=white blood cell.

      WHAT WAS THE LEVEL AND DURATION OF CYP3A INHIBITOR USE IN VIALE-A?

      Anti-infective prophylaxis was required for patients with ANC<500/μL2

      CYP3A INHIBITOR USE IN THE FIRST 2 CYCLES IN VIALE A2
      VIALE-A study design

      MEDIAN DURATION OF PROPHYLACTIC CYP3A INHIBITOR USE2

      Examples of moderate anti-infective CYP3A inhibitors include fluconazole, erythromycin and ciprofloxacin. Examples of strong anti-infective CYP3A inhibitors include itraconazole, posaconazole and voriconazole1

      More guidance on managing drug-drug interactions is available in DDI management

      Please refer to SmPC for full prescribing information.

      *For any end date that was not available, the end date was the date of study cut.

      ANC=absolute neutrophil count; AZA=azacitidine; CYP3A=cytochrome P450 3A; CYP3Ai=CYP3A inhibitor; VEN=VENCLYXTO. 

      WHAT IS THE DOSE ADJUSTMENT OF VENCLYXTO IN THE PRESENCE OF CYP3A INHIBITORS?

      Concomitant use of VENCLYXTO with strong or moderate CYP3A inhibitors increases VENCLYXTO exposure and may increase the risk for TLS at initiation and during the dose titration phase and for other toxicities. Consider alternative medications1

      The SmPC recommends VENCLYXTO dose reductions when co-administered with moderate or strong CYP3A inhibitors. Patients should be monitored closely for signs of toxicities and the dose may need to be further adjusted1

      MAXIMUM DOSE OF VENCLYXTO WHEN USED IN COMBINATION WITH STRONG CYP3A INHIBITORS1

      After dose-titration phase, reduce to 100 mg or less (or by at least 75% if already modified for other reasons)

      MAXIMUM DOSE OF VENCLYXTO WHEN USED IN COMBINATION WITH MODERATE CYP3A INHIBITORS1

      Reduce VENCLYXTO dose by at least 50%

      More guidance on managing drug-drug interactions is available in DDI management

      Please refer to SmPC for full prescribing information.

      CYP3A=cytochrome P450 3A; P-gp=permeability glycoprotein.

      IS THERE ANY DATA ON USE OF VENCLYXTO WITH ANTIFUNGALS OTHER THAN AZOLES?

       

      PROPHYLACTIC MEDICATION USE IN VIALE-A3

      GENERIC NAME, N (%)VEN + AZA (N=286)AZA ALONE (N=145)
      Prophylactic medication in ~5% of patients 236 (83)117 (81)
      Aciclovir79 (28)37 (26)
      Amphotericin B14 (5)7 (5)
      Caspofungin16 (6)6 (4)
      Cefepime24 (8)10 (7)
      Ciprofloxacin43 (15)20 (14)
      Co-amoxiclav23 (8)9 (6)
      Fluconazole44 (15)26 (18)
      Levofloxacin85 (30)47 (32)
      Meropenem30 (11)11 (8)
      Micafungin27 (9)8 (6)
      Piperacillin/tazobactam35 (12)19 (13)
      Posaconazole43 (15)21 (15)
      Trimethoprim/sulfamethoxazole57 (20)20 (14)
      Valaciclovir34 (12)15 (10)
      Voriconazole17 (6)8 (6)
      GENERIC NAME, N (%)VEN + AZA (N=286)
      Prophylactic medication in ~5% of patients 236 (83)
      Aciclovir79 (28)
      Amphotericin B14 (5)
      Caspofungin16 (6)
      Cefepime24 (8)
      Ciprofloxacin43 (15)
      Co-amoxiclav23 (8)
      Fluconazole44 (15)
      Levofloxacin85 (30)
      Meropenem30 (11)
      Micafungin27 (9)
      Piperacillin / tazobactam35 (12)
      Posaconazole43 (15)
      Trimethoprim / sulfamethoxazole57 (20)
      Valaciclovir34 (12)
      Voriconazole17 (6)
      GENERIC NAME, N (%)AZA ALONE (N=145)
      Prophylactic medication in ~5% of patients 117 (81)
      Aciclovir37 (26)
      Amphotericin B7 (5)
      Caspofungin6 (4)
      Cefepime10 (7)
      Ciprofloxacin20 (14)
      Co-amoxiclav9 (6)
      Fluconazole26 (18)
      Levofloxacin47 (32)
      Meropenem11 (8)
      Micafungin8 (6)
      Piperacillin / tazobactam19 (13)
      Posaconazole21 (15)
      Trimethoprim / sulfamethoxazole20 (14)
      Valaciclovir15 (10)
      Voriconazole8 (6)
      • Amphotericin B, caspofungin and micafungin were all used by patients during VIALE-A3

      AbbVie does not provide recommendations regarding the combination of VENCLYXTO with specific agents for anti-infective prophylaxis for bacterial, viral and fungal infections1

      Please refer to individual SmPCs before prescribing

      More guidance on managing drug-drug interactions is available in DDI management

      AZA=azacitidine; VEN=VENCLYXTO.

      DOES USE OF ANTIMICROBIAL PROPHYLAXIS IMPACT PATIENT OUTCOMES WITH VENCLYXTO?

      Antimicrobial prophylaxis with CYP3A inhibitors was used in neutropenic patients in the VIALE-A study, with overall similar composite remission rates with VENCLYXTO dose reductions2*

      OVERALL SURVIVAL

      Median OS in patients receiving VEN+AZA was not statistically different regardless of use of moderate or strong CYP3A inhibitor2

      ADVERSE EVENTS

      Rates of discontinuation from infections were similar across all patients treated with VEN+AZA regardless of CYP3Ai use2

      RESPONSES

      Rates of CR+CRi as best response in the VEN+AZA arm of VIALE-A were similar with concomitant use of CYP3Ai vs. no use2

      More guidance on managing drug-drug interactions is available in DDI management

      Graphs adapted from Jonas BA et al.

      VIALE-A was a phase 3, randomised (2:1), placebo-controlled, trial evaluating the efficacy and safety of VEN+AZA vs. PBO+AZA in first-line adult AML patients ineligible for intensive chemotherapy. VEN+AZA acheived its primary endpoints, achieving statistically significant increases in overall survival and CR+CRi rate vs AZA alone (p<0.001 for both).3

      *Neutropenic patients were defined as having an ANC <500/µL.2

      ANC=absolute neutrophil count; CI=confidence interval; CR=complete remission; CRi=CR with incomplete count recovery; CYP3Ai=cytochrome P450 3A inhibitor;
      OS=overall survival; VEN=VENCLYXTO. 

      WHEN STOPPING CY3PA INHIBITORS, HOW IS VENCLYXTO DOSE-TITRATED FROM THE REDUCED DOSE TO THE FULL DOSE?

      The VENCLYXTO dose that was used prior to concomitant use of a strong or moderate CYP3A inhibitor should be resumed 2 to 3 days after discontinuation of the inhibitor1

      More guidance on managing drug-drug interactions is available in DDI management

      HOW IS REMISSION DEFINED IN VIALE-A AND THE SMPC?

      VIALE A

      Complete remission was defined as ANC >1,000/microlitre, platelets >100,000/microlitre, red blood cell transfusion independence, and bone marrow with <5% blasts.3

      SmPC

      Complete remission was defined as ANC >1,000/microlitre, platelets >100,000/microlitre, red blood cell transfusion independence, and bone marrow with <5% blasts. Absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease.1

      ANC=absolute neutrophil count.

      HOW IS CYTOPENIA MANAGED PRIOR TO AND AFTER REMISSION?

      Management of some adverse reactions may require dose interruptions or permanent discontinuation of VENCLYXTO1,4

      Grade 4 neutropenia with or without fever or infection; or Grade 4 thrombocytopenia* 

      OCCURRENCEDOSE MODIFICATIONS
      Occurrence prior to achieving remission†In most instances, do not interrupt VENCLYXTO in combination with AZA due to cytopenias prior to achieving remission
      First occurrence after achieving remission and lasting at least 7 days

      Delay subsequent cycle of VENCLYXTO and AZA and monitor blood counts.
      Administer G-CSF if clinically indicated for neutropenia.
      Upon resolution to Grade 1 or 2:

      • Resume VENCLYXTO at the same dose in combination with AZA
      Subsequent occurrences in cycles after achieving remission and lasting 7 days or longer 

      Delay subsequent cycle of VENCLYXTO and AZA and monitor blood counts.
      Administer G-CSF if clinically indicated for neutropenia.
      Upon resolution to Grade 1 or 2:

      • Resume VENCLYXTO at the same dose in combination with AZA, and
      • Reduce VENCLYXTO duration by 7 days during each of the subsequent cycles, such as 21 days instead of 28 days.

      Refer to AZA Prescribing Information for additional information.

      Grade 3 or 4 non-haematological toxicities 

      OCCURRENCEDOSE MODIFICATIONS
      Any occurrence

      Interrupt VENCLYXTO if not resolved with supportive care
      Upon resolution to Grade 1 or baseline level:

      • Resume VENCLYXTO at the same dose

      More guidance on managing cytopenia is available in Cytopenia & AE management

      Please refer to the SmPC for full safety information

      *Grade 4 neutropenia (ANC <500/μL) with or without fever or infection; or Grade 4 thrombocytopenia (platelet count <25,000/μL).1

      †Consider bone marrow evaluation to assess remission.1

      ANC=absolute neutrophil count; AZA=azacitidine.

      IN VIALE-A, WHAT WAS THE INCIDENCE OF DOSE INTERRUPTIONS AND CYCLE DELAYS?

      Cycle delays and reduction in dosing duration and/or cycle delay ≥7 days related to Grade 4 cytopenia were more frequent in the VEN+AZA arm.

      CYCLE DELAY RELATED TO GRADE 4 CYTOPENIA AFTER BLAST CLEARANCE AMONG PATIENTS  WHO ACHIEVED CR/CRh4

      REDUCTION IN DOSING DURATION AND/OR CYCLE DELAY ≥7 DAYS RELATED TO GRADE 4 CYTOPENIA AMONG PATIENTS WHO ACHIEVED CR/ CRh4

      CYCLE DELAY RELATED TO GRADE 4 CYTOPENIA AFTER BLAST CLEARANCE AMONG PATIENTS  WHO ACHIEVED CR/CRh4

      REDUCTION IN DOSING DURATION AND/OR CYCLE DELAY ≥7 DAYS RELATED TO GRADE 4 CYTOPENIA AMONG PATIENTS WHO ACHIEVED CR/ CRh4

      MEDIAN DURATION OF CYCLE DELAY AMONG PATIENTS WHO ACHEIVED CR/CRh4

      MEDIAN NUMBER OF CYCLES FROM REMISSION TO FIRST TREATMENT BREAK OF  ≥ 7 DAYS AMONG PATIENTS WHO ACHIEVED CR/CRh4

      MEDIAN DURATION OF CYCLE DELAY AMONG PATIENTS WHO ACHEIVED CR/CRh4

      MEDIAN NUMBER OF CYCLES FROM REMISSION TO FIRST TREATMENT BREAK OF  ≥ 7 DAYS AMONG PATIENTS WHO ACHIEVED CR/CRh4

      More guidance on managing cytopenia is available in Cytopenia & AE management

      AZA=azacitidine; CR=complete remission; CRh=CR with partial haematologic recovery; VEN=VENCLYXTO.

      VIALE-A study design

      HOW MANY PATIENTS RECEIVED A GRANULOCYTE-COLONY STIMULATING FACTOR (G-CSF) IN THE VIALE-A STUDY?

      In VIALE‑A, 190/286 patients (66%) treated with VEN+AZA achieved CR/CRi. Of those, 49% (93/190) received G‑CSF after achieving remission5 

      Post-remission G-CSF use was not associated with inferior duration of CR/CRi or inferior OS among patients treated with VENCLYXTO in VIALE-A5

      More guidance on managing cytopenia is available in Cytopenia & AE management

      AZA=azacitidine; CR=complete remission; CRi=CR with incomplete count recovery; remission; G-CSF=granulocyte-colony stimulating factor; NR=not reached; OS=overall survival; VEN=VENCLYXTO.

      WHEN STOPPING CY3PA INHIBITORS, HOW IS VENCLYXTO DOSE-TITRATED FROM THE REDUCED DOSE TO THE FULL DOSE?

      The VENCLYXTO dose that was used prior to concomitant use of a strong or moderate CYP3A inhibitor should be resumed 2 to 3 days after discontinuation of the inhibitor1

      More guidance on managing drug-drug interactions is available in DDI management

      WHAT ARE THE COMMON AND SERIOUS ADVERSE EVENTS REPORTED IN VIALE-A?

      In the VIALE-A study, the most commonly occurring adverse reactions (≥20%) of any grade in patients receiving VEN+AZA were thrombocytopenia, neutropenia, febrile neutropenia, nausea, diarrhoea, vomiting, anaemia, fatigue, pneumonia, hypokalaemia, and decreased appetite.1

      The most frequently reported serious adverse reactions (≥5%) in patients receiving VEN+AZA were febrille neutropenia, pneumonia, sepsis and haemorrhage.1

      Please refer to the SmPC for full safety information

      IS VENCLYXTO ROUTINELY COMMISSIONED ACROSS THE UK?

      VENCLYXTO in combination with azacitidine is routinely reimbursed across the UK for the treatment of adult patients with newly diagnosed acute myeloid leukaemia (AML) who are ineligible for intensive chemotherapy.6,7

      References

      1. VENCYLXTO Summary of Product Characteristics.
      2. Jonas BA et al. Poster 2846. ASH 62nd; Dec 5-8, 2020; Virtual.
      3. DiNardo CD et al. N J Med. 2020; 383(7): 617-29 and Supplementary appendix.
      4. Pratz K, et al. Oral presentation 1944. ASH 62nd; Dec 5-8, 2020; Virtual.
      5. DiNardo CD et al. Poster P510 EHA2022 Hybrid Congress, June 9–17, 2022, Vienna, Austria 
      6. NICE TAG 765: https://www.nice.org.uk/guidance/ta765 (accessed April 2024)
      7. SMC2412: https://www.scottishmedicines.org.uk/medicines-advice/venetoclax-venclyxto-full-smc2412/
        (accessed April 2024)

       

      OVERALL SURVIVAL

      Median OS in patients receiving VEN+AZA was not statistically different regardless of use of moderate or strong CYP3A inhibitor2*

      Adapted from Jonas BA et al.

      *As noted by overlapping confidence intervals.

      ADVERSE EVENTS

      Rates of discontinuation from infections were similar across all patients treated with Ven+AZA regardless of CYP3Ai use2*

      Graph adapted from Jonas BA et al.

      *Reported AEs that began within the the first 2 cycles of treatment with CYP3Ai were reported as being given for prophylaxis.

      RESPONSES

      Rates of CR+CRi as best response in the VEN+AZA arm of VIALE-A were similar with concomitant use of CYP3Ai vs. no use2*

      Graph adapted from Jonas BA et al.

      *CR=absolute neutrophil count (ANC) >1,000/microlitre, platelets >100,000/microlitre, RBC transfusion independence, and bone marrow with <5% blasts. Absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease.

      CRi=ANC ≤1,000/microlitre or platelets ≤100,000/microlitre1

      Adverse events should be reported. Reporting forms and information can be found at https://yellowcard.mhra.gov.uk or via the MHRA Yellow Card app, available in the Google Play or Apple App Stores. Adverse events should also be reported to AbbVie on GBPV@abbvie.com

       

      This website is for UK Healthcare Professionals only

      UK-ABBV-230225. Date of preparation June 2023. This website has been developed and funded by AbbVie Ltd.

      © 2023 AbbVie Ltd. All rights reserved. Registered Number: 08004972 England.