Phase 3 Trial of Ibrutinib plus Rituximab in Waldenström’s Macroglobulinemia
- Study type
- Clinical trial
- Study name
- iNNOVATE
- Phase
- Phase 3
- Design
- Randomised, placebo-controlled trial
- Sample size
- 150 patients
- Source
- N Engl J Med · 2018
- Trial registration
- NCT02165397
In plain words
Waldenström's macroglobulinaemia is a rare cancer that belongs to the lymphoma family. In this study, adding the drug ibrutinib to rituximab meant that patients stayed much longer without their disease getting worse, whether or not they had been treated before. On the other hand, problems such as an irregular heart rhythm (atrial fibrillation) and high blood pressure were seen more often in patients taking ibrutinib, so close follow-up by a doctor is essential.
Key results
Treatment arms and regimens
Ibrutinib 420 mg orally daily from day 1 + rituximab 375 mg/m² IV weekly for 4 consecutive weeks, followed by a second 4-week course after a 3-month interval.
Oral placebo daily from day 1 + rituximab on the same schedule (375 mg/m² weekly × 4, repeated after 3 months).
Source of the regimen details: ClinicalTrials.gov NCT02165397
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 symptomatic Waldenström's macroglobulinaemia (a rare B-cell lymphoma), including both previously untreated patients and patients with relapsed disease.
Endpoints
Primary endpoint: progression-free survival assessed by an independent review committee. Key secondary endpoints: response rate, sustained haematological improvement from baseline and safety. MYD88 and CXCR4 mutation status was assessed in bone marrow samples.
Safety and side effects
The most common adverse events of any grade in the ibrutinib–rituximab group were infusion-related reactions, diarrhoea, arthralgia and nausea. Grade 3 or higher adverse events that were more common in the ibrutinib–rituximab group: atrial fibrillation (12% versus 1%) and hypertension (13% versus 4%). Events that occurred less often: infusion reactions (1% versus 16%) and IgM flare of any grade (8% versus 47%). The rate of major bleeding was the same in the two groups (4%).
Clinical significance and place in guidelines
This trial showed that ibrutinib plus rituximab in Waldenström's macroglobulinaemia, in both untreated and relapsed patients, significantly improves progression-free survival, and that this benefit is independent of MYD88 or CXCR4 genotype. The risk of atrial fibrillation and hypertension should be considered when choosing treatment. The status of regulatory approvals and guideline recommendations should be checked separately.
Limitations
The abstract does not mention the study's limitations. The study was funded by Pharmacyclics and Janssen Research and Development. Further details in the full text.
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.