A newer report of this study has been published: Long-term outcomes for ibrutinib-rituximab and chemoimmunotherapy in CLL: updated results of the E1912 trial (2022)
In this study, people aged 70 or younger with chronic lymphocytic leukaemia who had not yet been treated received either the drugs ibrutinib and rituximab or chemotherapy combined with immunotherapy (FCR). People who received ibrutinib and rituximab stayed free of disease progression for longer and had better overall survival. Serious infections were seen less often in this group, although the overall rate of serious side effects was similar in the two groups.
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: Full text of the NEJM 2019 paper in PMC (PMC6908306), Methods section; FDA label for ibrutinib (DailyMed) for the creatinine clearance criterion
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.
Primary endpoint: progression-free survival. Overall survival was a secondary endpoint. Results are from a prespecified interim analysis.
The incidence of grade 3 or higher adverse events (regardless of attribution) was similar in the two groups: 282 of 352 patients (80.1%) in the ibrutinib–rituximab group and 126 of 158 patients (79.7%) in the chemoimmunotherapy group. Grade 3 or higher infectious complications were less frequent in the ibrutinib–rituximab group (10.5% versus 20.3%; P<0.001).
This trial showed that in patients aged 70 or younger with untreated CLL, ibrutinib–rituximab is superior to the standard FCR regimen in progression-free and overall survival. The superiority was clear in patients with unmutated IGHV, whereas in patients with mutated IGHV the difference in 3-year progression-free survival between the groups was negligible. These results are from an interim analysis. The status of approvals and the place of this regimen in treatment guidelines should be checked in up-to-date sources.
Results are from an interim analysis with a median follow-up of 33.6 months. The subgroup analysis by IGHV status had a wide confidence interval in mutated patients (HR 0.44; 95% CI 0.14–1.36). The study population was limited to patients aged 70 or younger.
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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