Venetoclax Approval Tracker + Quizz

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Last Update 30 May 2020

Disease Group Non 1st Line Approval Non 1st Line Approval 1st Line Approval 1st Line Approval
Chronic lymphocytic leukemia (CLL)  Single Agent Combination Single Agent Combination
Approval Year Apr-16 Jun-18 May-19
Landmark Trial Phase III MURANO study CLL14 trial
Single Agent/Combination Single Agent With Rituximab With obinutuzumab
Chronic lymphocytic leukemia (CLL) CLL with 17p deletion after at least one prior therapy CLL with or without 17p deletion after at least one prior therapy Previously untreated CLL patients
Disease Group Non 1st Line Approval Non 1st Line Approval 1st Line Approval 1st Line Approval
Acute Myeloid Leukemia (AML) Single Agent Combination Single Agent Combination
Approval Year Nov-18
Landmark Trial M14-358 study and M14-387 study
Single Agent/Combination Combination with
(1) Hypomethylating agent (azacitidine or decitabine)
(2) Low-dose cytarabine (LDAC)
Acute Myeloid Leukemia (AML) Newly-diagnosed AML
(1) Age 75 years or older
(2) Those ineligible for intensive induction chemotherapy due to coexisting medical conditions

 

Dosing Schedule

[1] CLL

Ramp Up Schedule for CLL

Week 1 Week 2 Week 3 Week 4 Week 1 
Cycle 1 = 28 days Cycle 2 = 28 days
20 mg OD 50 mg OD 100 mg OD 200 mg OD 400 mg OD

Single agent

The recommended dose of venetoclax is 400 mg once daily after the patient has completed the 5-week dose ramp-up schedule. Venetoclax should be taken orally once daily until disease progression or unacceptable toxicity is observed.

Combination with Obinutuzumab

Cycle 1 = 28 days Cycle 2
Week 1 Week 2 Week 3 Week 4 Week 1
x x x Start Venetoclax as per ramp up schedule and continue till cycle 12
Obinutuzumab
100 mg on Cycle 1 D 1

900 mg on Cycle 1 D2

 1000 mg on Days 8 1000 mg on Days 15 1000 mg on Days 1 of each cycle from cycle 2-6

Combination with Rituximab

Start rituximab administration after the patient has completed the 5-week dose ramp-up schedule with Venetoclax and has received the 400 mg dose of Venetoclax for 7 days. ie Cycle count starts at week 6 of therapy.

Cycle 1 Cycle 2
Venetoclax has been given for 5 weeks 400 mg OD 400 mg OD x 24 months
Rituximab start after 5 weeks of Venetoclax and cycle count starts from 1st R administration only 375 mg/m2 on day 1 500 mg/m2 on day 1 (Cycle 2-6)

 

2 AML

With HMA (Azacytidine/Decitabine) or LDAC (Low Dose ARA C)

Cycle 1 = 28 days Cycle 2 = 28 days
Week 1 Week 2 Week 3 Week 4 Week 1
Venetoclax untill progression or unacceptable toxicity
  • D1 = 100 mg OD
  • D2 = 200 mg OD
  • D3 = 400 mg OD
  • D4 0nwards 400 mg OD for HMA and 600 mg for LDAC
 400 mg OD for HMA and 600 mg for LDAC
AZA = 75 mg/m2 days 1-7 SC every cycle untill progression or unacceptable toxicity Same as in cycle 1
Decitabine = 20 mg/m2 days 1-5 SC every cycle untill progression or unacceptable toxicity Same as in cycle 1
LDAC = 20 mg/m2 days 1-10 SC every cycle untill progression or unacceptable toxicity Same as in cycle 1

References:

  1. 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.
  2. Fischer K, Al-Sawaf O, Bahlo J, et al. Venetoclax and obinutuzumab in patients with CLL and coexisting conditions. N Engl J Med. 2019;380(23):2225-2236.
  3. Kater AP, Seymour JF, Hillmen P, et al. Fixed duration of venetoclax-rituximab in relapsed/
    refractory chronic lymphocytic leukemia eradicates minimal residual disease and prolongs survival: post-treatment follow-up of the
    MURANO phase III study. J Clin Oncol. 2019;37(4):269-277.
  4. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/208573s013lbl.pdf

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