Treatment naïve CLL patients with high risk profile randomized between treatment with 6 cycles of FC and FCA.
Evaluated 119/272 (43.8%) trial patients.
75 (63%) patients with subclonal mutation and/or chromosomal abnormality in this cohort.
Subclonal mutations had lower ORR.
ORR and CR decreased in patients with TP53 mutation but not in those with other mutations.
FCA improved ORR in patients with TP53 mutations.
Patients with other mutations: no differences in ORR/CR between two treatment arms.
- Median follow-up of 42.5 months PFS tends to be shorter in patients with subclonal mutations.
- PFS was only significantly decreased in patients with TP53 mutation (p<0.001).
FCA improved PFS in patients with mutated TP53 and SF3B1 mutation.
OS was only decreased in TP53 mutated.
Trend for improved OS due to FCA (median 24 vs 67 months; p=0.09).
Majority of novel recurrent mutations and chromosomal abnormalities subclonal.
Subclonality associated with inferior outcome.
TP53 mutations had an adverse prognostic impact, overcome by alemtuzumab.
SF3B1 mutation might benefit from alemtuzumab.
- Though it does show benefit of Alemtuzumab, it is of unclear clinical implication as there was no Rituximab arm.
View the original abstract on the ASH website.
