Untreated CLL in patients aged 70 years or younger without del(17p), with CrCl greater than 40 mL/min
| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Ibrutinib | 420 mg once daily | Oral | Continuous from Cycle 1 |
| From Cycle 2 (6 cycles) | |||
| Rituximab | 50 mg/m² Day 1 and 325 mg/m² Day 2 of Cycle 2; then 500 mg/m² | IV | Day 1 of Cycles 3–7 |
Untreated CLL in patients aged 70 years or younger without 17p deletion, with CrCl above 40 mL/min
| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Ibrutinib | 420 mg once daily | Oral | Continuous from cycle 1 |
| From cycle 2 (6 cycles) | |||
| Rituximab | 50 mg/m² on Day 1 and 325 mg/m² on Day 2 of cycle 2; then 500 mg/m² | IV | Day 1 of cycles 3–7 |
Rituximab boxed warning: fatal infusion-related reactions, HBV reactivation and PML.
On the page “Leukaemia” · Regimens and dosing in CLL: continuous BTK inhibitor therapy
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.
Ibrutinib 420 mg orally daily from cycle 1 until disease progression or unacceptable toxicity, + rituximab from cycle 2: 50 mg/m² on day 1 of cycle 2, 325 mg/m² on day 2 of cycle 2 and 500 mg/m² on day 1 of cycles 3 to 7 (6 cycles); each cycle 28 days. All patients received allopurinol 300 mg daily on days 1 to 14 of cycle 1.
Six 28-day cycles: fludarabine 25 mg/m² and cyclophosphamide 250 mg/m² IV on days 1 to 3 + rituximab 50 mg/m² on day 1 of cycle 1, 325 mg/m² on day 2 of cycle 1 and 500 mg/m² on day 1 of cycles 2 to 6. Allopurinol 300 mg daily on days 1 to 14 of cycle 1.
Source of the regimen details: Regimen of the original E1912 trial: full text of the NEJM 2019 paper in PMC (PMC6908306); safety from the full text of the Blood 2022 paper in PMC (PMC9283968)
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 aged 70 years or younger with untreated CLL or SLL with an indication for treatment by iwCLL criteria. Patients with 17p13 deletion were not enrolled (because of poor response to FCR); all patients had creatinine clearance above 40 mL/min. Randomisation was stratified by age (under 60 versus 60 to 70 years), ECOG, Rai stage and 11q22.3 deletion.
Progression-free survival, overall survival and tolerability of continuous ibrutinib.
With long follow-up, treatment-related grade ≥3 adverse events occurred in 73.0% of IR patients and 83.5% of FCR patients (OR 0.53). Important grade 3 to 5 adverse events (IR versus FCR): hypertension 11.4% versus 1.9%, cardiac events 7.7% versus 0% (atrial fibrillation 4.5%), decreased neutrophils 28.4% versus 45.6%, anaemia 4.3% versus 15.8%, infection 11.4% versus 19.6% and febrile neutropenia 2.3% versus 15.8%. Grade ≥3 bleeding occurred in 4 patients (1.1%) in the IR group. 21.9% of patients in the IR group stopped ibrutinib because of adverse events or treatment complications.
This follow-up confirmed the long-term superiority of ibrutinib over FCR in younger patients, including in IGHV-mutated CLL, and further limited the role of chemoimmunotherapy in the first line.
About one in five patients stopped ibrutinib because of adverse events; treatment is continuous.
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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