Long-term remissions after FCR chemoimmunotherapy in previously untreated patients with CLL: Updated results of the CLL8 trial

Despite promising results with targeted drugs, chemoimmunotherapy with fludarabine, cyclophosphamide (FC), and rituximab (R) remains the standard therapy for fit patients with untreated chronic lymphocytic leukemia (CLL). Herein, we present the long-term follow-up of the randomized CLL8 trial reporting safety and efficacy of FC and FCR treatment of 817 treatment-näivepatientswithCLL.The primary end pointwas progressionfree survival (PFS). With a median follow-up of 5.9 years, median PFS were 56.8 and 32.9 months for theFCRand FCgroup (hazardratio[HR], 0.59; 95%confidence interval [CI], 0.50- 0.69, P< .001).Median overall survival (OS)was not reached for the FCRgroup and was 86.0 months for the FC group (HR, 0.68; 95% CI, 0.54-0.89, P 5 .001). In patients with mutated IGHV(IGHVMUT),FCRimprovedPFSandOScomparedwithFC(PFS:HR, 0.47; 95%CI, 0.33-0.68,P<.001;OS:HR, 0.62; 95%CI,0.34-1.11, P=.1).This improvement remainedapplicable for all cytogenetic subgroups other thandel(17p).Long-termsafety analysesshowed that FCR had a higher rate of prolonged neutropenia during the first year after treatment (16.6% vs 8.8%; P = .007). Secondarymalignancies includingRichter's transformationoccurred in 13.1%in theFCRgroupandin17.4%in theFCgroup(P=.1). First-linechemoimmunotherapy with FCR induces long-term remissions and highly relevant improvement in OS in specific genetic subgroups of fit patients with CLL, in particular those with IGHV MUT.