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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) |
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| 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 |
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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 | ||||
|
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:
- 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.
- 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.
- 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. - https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/208573s013lbl.pdf