Long-term data from the phase III HELIOS trial indicates ibrutinib plus bendamustine and rituximab improve survival outcomes in CLL patients.
Long-term data from the phase III HELIOS trial indicated that ibrutinib plus bendamustine and rituximab (BR) significantly improved survival outcomes for patients with relapsed chronic lymphocytic leukemia (CLL) or small lymphocytic leukemia (SLL). In addition, the drug combination resulted in increased response rates over time.
“It is notable that longer-term follow-up revealed a significant improvement in survival for ibrutinib plus BR-treated patients compared with placebo plus BR, despite the possibility of crossover after progression,” noted researchers led by G. Fraser, of Juravanski Cancer Centre, McMaster University, Hamilton, Ontario. “Additionally, deeper responses were reported with continuous ibrutinib therapy, with rates of investigator-assessed CR (complete response)/CRi (complete remission with incomplete blood count) and MRD (minimal residual disease)-negative response rising to 38% and 26%, respectively (compared with IRC-assessed rates of 21% and 13% at the primary analysis).”
In the trial, 578 patients were randomly assigned to ibrutinib 420 mg daily or placebo combined with 6 cycles of BR followed by ibrutinib or placebo alone. The median follow-up was 34.8 months.
At this longer follow-up, the investigator-assessed median progression-free survival (PFS) was not reached for ibrutinib plus BR compared with 14.3 months for placebo plus BR (hazard ratio [HR], 0.206; 95% CI, 0.159–0.265; P < .0001). At 36-months the PFS rate was 68% compared with 13.9% for placebo. The researchers noted that these results were consistent with those from the primary analysis as assessed by independent review committee at 17 months median follow-up (HR = 0.203).
The 36-month overall survival (OS) rate was 81.6% for ibrutinib plus BR compared with 72.9% for placebo plus BR. The median OS rate was not yet reached in either arm, but was significantly longer for ibrutinib (HR, 0.652; 95% CI, 0.454–0.935; P = .019).
Investigator-assessed overall response rate was 87.2% for ibrutinib plus BR compared with 66.4% for placebo plus BR (P < .0001). CR/CRi was 38.1% for the combination compared with 8% for placebo. The researchers assessed 211 patients in the ibrutinib arm and 76 patients in the placebo arm for MRD. MRD-negative response rates in peripheral blood or bone marrow was 26.3% for intent-to-treat population assigned to ibrutinib plus BR compared with 6.2% for placebo plus BR (P < .0001).
Rates of treatment-emergent adverse events were consistent with the primary analysis. Eight additional patients in the ibrutinib arm had atrial fibrillation/flutter during follow-up, which was “consistent with reviews and meta-analyses documenting an increased risk of developing AF in ibrutinib-treated patients versus comparator treatments.”
“These long-term follow-up data support improved survival outcomes with ibrutinib plus BR compared with BR alone in relapsed CLL/SLL,” the researchers wrote.