Long-term results from the international, open-label, randomized phase 3 trial comparing single-agent ibrutinib to ofatumumab in high-risk relapsed patients with chronic lymphocytic leukemia (CLL) (RESONATE; ClinicalTrials.gov Identifier: NCT01578707) showed sustained efficacy and safety of ibrutinib in these patients. The study was published online in Blood.1
The majority of patients diagnosed with CLL experience disease relapse following initial treatment with chemoimmunotherapy. At a median follow-up of 9.4 months, previously reported results from the phase 3 RESONATE trial comparing ibrutinib with ofatumumab in patients with relapsed/refractory CLL or small lymphocytic lymphoma (SLL) who were considered inappropriate for purine analogue therapy showed that median progression-free survival (PFS) (P <.001) and overall survival (OS) (P =.005) were significantly longer for patients randomly assigned to the ibrutinib arm compared with the ofatumumab arm.2
Pneumonia (7%), urinary tract infection (4%), and diarrhea (4%) were the most frequent grade 3 or higher nonhematologic adverse events for patients in the ibrutinib arm, and neutropenia (16%), followed by thrombocytopenia (6%) and anemia (5%) were the most common grade 3 or higher hematologic adverse events observed in this group.
Some of the key findings of long-term follow-up (ie, median follow-up of 44 months) for patients enrolled in the RESONATE trial include the following:
- Median PFS was not reached for patients receiving ibrutinib vs 8.1 months for those receiving ofatumumab
- PFS remained significantly longer for ibrutinib vs ofatumumab (hazard ratio [HR]=0.133; 95% confidence interval [CI], 0.099-0.178; P <.0001)
- 3-year PFS rate was 59% with ibrutinib vs 3% with ofatumumab
- On multivariate analysis, more than 2 lines of therapy (P =.007) and elevated baseline beta-2 microglobulin levels (P =.044) were significantly associated with decreased PFS for patients receiving ibrutinib
- There was a continued trend for improved OS for patients assigned to the ibrutinib arm despite 68% of patients assigned to the ofatumumab arm crossing over to ibrutinib
- 3-year OS rates of 74% in the ibrutinib arm and 65% in the ofatumumab arm (irrespective of crossover)
- Following censoring for crossover, OS was significantly longer for patients randomly assigned to the ibrutinib arm compared with those assigned to the ofatumumab arm (HR=0.591; 95% CI, 0.378-0.926; P =.0208)
- 91% of patients receiving ibrutinib experienced a response; and overall response increased over time
- The most common grade 3 or higher hematologic adverse events included neutropenia (23%), anemia (9%) and thrombocytopenia (8%). Pneumonia (17%), hypertension (8%), urinary tract infection (6%), atrial fibrillation (6%), and diarrhea (6%) were the most frequent grade 3 or higher nonhematologic adverse events occurring on long-term follow-up.
- Byrd JC, Hillmen P, O’Brien S, et al. Long-term follow-up of the RESONATE™ phase 3 trial of ibrutinib versus ofatumumab [published online March 6, 2019]. Blood. doi: 10.1182/blood-2018-08-870238
- Byrd JC, Brown JR, O’Brien S, et al. Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia. N Engl J Med. 2014;371:213-223.