Dr Niemann on the Investigation of Ibrutinib Plus Ventoclax in CLL

“We already knew that PFS was improved with the ibrutinib combination. The question now was: Would this improvement be sustainable for a longer period of follow up? That's what we found in the longer-term follow-up data. [Moreover], the toxicity-free PFS was significantly improved by more than 20 months with ibrutinib and venetoclax vs chlorambucil and obinutuzumab, despite the longer length of treatment.”

Carsten Niemann, MD, PhD, chief physician, head, Laboratory at the Rigshospitalet Copenhagen University Hospital, discusses long-term follow-up data with fixed-duration ibrutinib (Imbruvica) plus venetoclax (Venclexta) in elderly or comorbid patients with previously untreated chronic lymphocytic leukemia (CLL) from the phase 3 GLOW trial (NCT03462719). These findings were presented at the 2024 ASH Annual Meeting.

The phase 3 GLOW study compared the safety and efficacy of a fixed-duration regimen of ibrutinib plus venetoclax with chlorambucil plus obinutuzumab (Gazyva) in patients with CLL. At a median follow-up of 64 months, the combination of ibrutinib and venetoclax significantly improved progression-free survival (PFS), reducing the risk of progression or death by 73% compared with the chlorambucil/obinutuzumab regimen (HR, 0.27; 95% CI, 0.18-0.39; P < .0001). The 60-month PFS rates were 59.9% for ibrutinib plus venetoclax and 17.8% for chlorambucil plus obinutuzumab. The longer-term data confirmed the durability of the PFS benefit previously observed with the ibrutinib and venetoclax combination, Niemann states.

Additionally, the study assessed the toxicity profile of the ibrutinib and venetoclax regimen, particularly grade 3 or higher adverse effects, given the longer treatment duration compared with the control arm, Niemann reports. Overall, patients spent less time in the grade 3/4 treatment-emergent AE and progressive disease health state with the ibrutinib combination vs the control regimen. Further analysis showed that the PFS time free from grade 3/4 toxicity or relapse was extended by 21.4 months in the ibrutinib and venetoclax arm (51.6 months) relative to the chlorambucil and obinutuzumab arm (30.2 months; nominal P = .0052), Niemann reports. highlighting the combination’s favorable balance of clinical benefit and manageable toxicity despite the extended treatment duration, he concludes.