In patients with CLL who also had other illnesses, one year of treatment with venetoclax tablets and obinutuzumab injections kept the disease under control for a median of more than 6 years, compared with about 3 years with chlorambucil-obinutuzumab, and quality of life also declined later.
Untreated CLL (in CLL14, patients with comorbidities)
| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Cycle 1 | |||
| Obinutuzumab | 100 mg Day 1, 900 mg Day 2, 1,000 mg Days 8 and 15 | IV | Days 1, 2, 8 and 15 |
| Cycles 2–6 | |||
| Obinutuzumab | 1,000 mg | IV | Day 1 |
| From Day 22 of Cycle 1 | |||
| Venetoclax | Weekly ramp-up: 20, 50, 100, 200, then 400 mg | Oral, with food | Through the end of Cycle 12 at 400 mg |
Premedication before obinutuzumab.
Untreated CLL (in CLL14, patients with comorbidities)
| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Cycle 1 | |||
| Obinutuzumab | 100 mg (Day 1), 900 mg (Day 2), 1000 mg (Days 8 and 15) | IV | Days 1, 2, 8 and 15 |
| Cycles 2–6 | |||
| Obinutuzumab | 1000 mg | IV | Day 1 |
| From Day 22 of cycle 1: 5-week ramp-up | |||
| Venetoclax | 20, 50, 100, 200 and then 400 mg (one step each week) | Oral, with food | Until Day 28 of cycle 2 |
| Cycles 3–12 | |||
| Venetoclax | 400 mg once daily | Oral, with food | Continuous |
Give premedication before each obinutuzumab infusion; boxed warning: hepatitis B reactivation (screening mandatory) and PML.
On the page “Leukaemia” · Regimens and dosing in CLL: fixed-duration targeted therapy
Previously untreated (or treated) CLL/SLL
| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Cycle 1 | |||
| Obinutuzumab | Day 1: 100 mg; day 2: 900 mg; days 8 and 15: 1000 mg | IV | Days 1, 2, 8 and 15 |
| Cycles 2 to 6 | |||
| Obinutuzumab | 1000 mg | IV | Day 1 |
| From day 22 of cycle 1 (ramp-up ends on day 28 of cycle 2) | |||
| Venetoclax | Week 1: 20; week 2: 50; week 3: 100; week 4: 200; from week 5: 400 mg | Oral, with food and water | Once a day |
| Cycles 3 to 12 | |||
| Venetoclax | 400 mg | Oral | Daily |
On the page “Venetoclax (Venclexta)” · Dose and schedule (FDA label)
Previously untreated CLL (especially with comorbidities or a preference for fixed-duration treatment)
| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Cycle 1 | |||
| Obinutuzumab | 100 mg on day 1 and 900 mg on day 2, then 1000 mg | IV | Days 1 and 2, 8 and 15 |
| Cycles 2 to 6 | |||
| Obinutuzumab | 1000 mg | IV | Day 1 |
| From day 22 of cycle 1 | |||
| Venetoclax (ramp-up) | 20, 50, 100, 200 and 400 mg, one week each | Oral, with food | Daily |
| Until the end of cycle 12 | |||
| Venetoclax | 400 mg | Oral | Daily |
As in CLL14.
Dose source:.
On the page “Venetoclax and obinutuzumab in CLL (the 12-month CLL14 regimen)”
Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.
Obinutuzumab IV for 6 cycles of 28 days: cycle 1 day 1 100 mg and day 2 900 mg (or 1000 mg on day 1 according to the dose-splitting rules), 1000 mg on days 8 and 15 of cycle 1, then 1000 mg on day 1 of cycles 2 to 6.
Venetoclax orally with dose ramp-up from day 22 of cycle 1: 20 mg (days 22 to 28 of cycle 1), 50, 100 and 200 mg each for one week in cycle 2, then 400 mg daily from day 22 of cycle 2 until the end of cycle 12. Tumour lysis syndrome prophylaxis according to tumour burden (hydration, allopurinol from 2 to 3 days before venetoclax and laboratory monitoring at the 20 and 50 mg doses) per the label.
Obinutuzumab on the same schedule for 6 cycles + chlorambucil 0.5 mg/kg orally on days 1 and 15 of each 28-day cycle for 12 cycles.
Source of the regimen details: Regimen of the primary CLL14 trial: ClinicalTrials.gov NCT02242942 (doses of venetoclax, obinutuzumab and chlorambucil) and the FDA label for venetoclax (DailyMed)
Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.
Patients with previously untreated CLL and coexisting conditions: CIRS score above 6 or calculated creatinine clearance below 70 mL per minute.
Primary endpoint: progression-free survival. Key secondary endpoints: time to next treatment, undetectable MRD, overall survival, adverse events and quality of life.
At 6-year follow-up, the follow-up-adjusted incidence rates of second primary malignancies were 2.3 and 1.4 per 1000 patient-months in the venetoclax-obinutuzumab and chlorambucil-obinutuzumab groups, respectively; 2 Richter transformations were reported in the venetoclax-obinutuzumab group and 4 in the chlorambucil-obinutuzumab group. In the primary analysis (NEJM 2019): grade 3 or 4 neutropenia in 52.8% versus 48.1% and grade 3 or 4 infection in 17.5% versus 15.0%.
The 6-year results establish one-year fixed-duration venetoclax-obinutuzumab as one of the first-line standards in CLL.
The difference in overall survival did not reach statistical significance (P=0.052); the comparator was chemoimmunotherapy.
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.
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