CRISTALLO phase III primary analysis: VenO vs FCR/BR in previously untreated CLL

Results from the primary analysis of the randomized, open-label, international phase III CRISTALLO study (NCT04285567), comparing first-line fixed-duration venetoclax + obinutuzumab (VenO; n = 80) vs fludarabine + cyclophosphamide + rituximab / bendamustine + rituximab (FCR/BR; n = 86) in patients with previously untreated chronic lymphocytic leukemia (CLL) without del(17p)/TP53 mutations, were published in Blood by Sharman et al. The primary endpoint was rate of undetectable measurable residual disease (<10⁻⁴; uMRD) at Month 15. Key secondary endpoints included uMRD in peripheral blood (PB) and bone marrow (BM) at the end of treatment (EoT) and investigator-assessed progression-free survival (PFS).

Key data: The primary endpoint was met; at Month 15, 81.3% vs 54.7% of patients in the VenO vs FCR/BR arms demonstrated uMRD in PB (p = 0.0004). At the EoT, uMRD rates were higher in the VenO vs FCR/BR arm in both PB (81.3% vs 60.5%; p = 0.0053) and BM (70.0% vs 38.4%; p < 0.0001). At data cutoff, median PFS was not reached due to the short survival follow-up. The 2‑year PFS rates were 95.7% vs 90.4% in VenO vs FCR/BR. The complete response (CR) / CR with incomplete blood count recovery (CRi) rate was higher with VenO vs FCR/BR (50.0% vs 32.6%). The overall response rates (ORRs) were 88.8% in VenO vs 79.1% in FCR/BR (p = 0.1119). In the safety evaluable population, Grade ≥3 adverse events (AEs) occurred in 83.1% of patients receiving VenO vs 81.2% of patients receiving FCR/BR.

Key learning: Results indicate that fixed-duration VenO demonstrated significantly greater improvements in MRD responses vs FCR/BR in fit, previously untreated patients with CLL. Longer follow-up is warranted to establish PFS outcomes.