Ibrutinib versus Ofatumumab in Previously Treated Chronic Lymphoid Leukemia
- Study type
- Clinical trial
- Study name
- RESONATE
- Phase
- Phase 3
- Design
- Multicentre, open-label (unblinded) randomised trial
- Sample size
- 391 patients
- Source
- N Engl J Med · 2014
- Trial registration
- NCT01578707
In plain words
In this study, patients with chronic lymphocytic leukaemia whose disease had come back after earlier treatment or had not responded to it received either the oral drug ibrutinib or the injected drug ofatumumab. Patients who took ibrutinib stayed longer without the disease getting worse, responded to treatment more often and lived longer. This advantage was also seen in patients with a high-risk genetic abnormality (17p13.1 deletion). Diarrhoea, tiredness, fever and nausea were common side effects of ibrutinib.
Key results
Treatment arms and regimens
Ibrutinib 420 mg orally once daily until disease progression or unacceptable toxicity.
Ofatumumab IV for up to 24 weeks (12 doses): 300 mg in week 1, then 2000 mg weekly in weeks 2 to 8, then 2000 mg every 4 weeks (weeks 12, 16, 20 and 24).
Source of the regimen details: Full text of the NEJM 2014 paper in PMC (PMC4134521) and ClinicalTrials.gov NCT01578707
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.
Study population
Patients with CLL or SLL requiring treatment who had received at least one prior therapy and were unsuitable for purine analogue treatment (short interval to progression after chemoimmunotherapy, comorbidities, age 70 or older, or 17p13.1 deletion). ECOG below 2, neutrophils at least 750 and platelets at least 30,000 per microlitre, and adequate liver and kidney function; patients requiring warfarin or a strong CYP3A4/5 inhibitor were not enrolled.
Endpoints
Primary endpoint: duration of progression-free survival. Secondary endpoints: duration of overall survival and overall response rate.
Safety and side effects
The most common non-haematological adverse events were diarrhoea, fatigue, pyrexia and nausea in the ibrutinib group, and fatigue, infusion-related reactions and cough in the ofatumumab group. Rates of grade 3 or higher adverse events are not reported in the abstract.
Clinical significance and place in guidelines
This trial showed that ibrutinib is superior to ofatumumab in relapsed or refractory CLL/SLL for progression-free survival, overall survival and response rate, including in patients with 17p13.1 deletion. The abstract gives no information on drug approvals or guideline position; the current status of guidelines should be checked separately.
Limitations
The study was open-label, and median follow-up was short (9.4 months). The control arm was ofatumumab, and comparison with other common regimens is not reported in the abstract.
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.