[Efficacy and long-term follow-up report of FCR regimen in the first-line treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma].

Objective: To evaluate the efficacy and long-term outcomes of fludarabine, cyclophosphamide, and rituximab (FCR) in treatment-naïve patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) . Methods: Clinical data from 68 CLL/SLL patients treated with FCR at Jiangsu Province Hospital (August 2008-May 2021) were retrospectively analyzed to assess efficacy, safety, and survival outcomes. Results: Among 68 patients [46 males, 22 females; median age 55 (47, 60) years], 13.1% (8/61) had a complex karyotype, 32.3% (20/62) had immunoglobulin heavy variable region mutated (IGHV-M) type, 6.6% (4/61) had del (17p), and 14.8% (8/54) had del (11q). Patients received a median of 6 (4, 6) FCR cycles. The overall response rate was 88.2% (60/68), including 47.0% (32/68) complete remissions. Over a median follow-up of 82 (59, 98) months, 66.2% (45/68) experienced disease progression. Median progression-free survival was 56 (21, 123) months, while median overall survival was not reached. The 5- and 10-year PFS rates were 42.6% (95% CI: 31.9-56.8% ) and 28.7% (95% CI: 19.0-43.4% ), respectively. Poor PFS was associated with del (17p) (HR=5.04, 95% CI: 1.72-14.74, P=0.003), del (11q) (HR=5.27, 95% CI: 2.11-13.15, P<0.001), IGHV unmutated (IGHV-UM) (HR=4.11, 95% CI: 1.72-9.79, P=0.001), complex karyotype (CK) (HR=3.53, 95% CI: 1.58-7.85, P=0.002), β(2)-microglobulin >3.5 mg/L (HR=2.87, 95% CI: 1.37-6.01, P=0.005). In multivariate analysis, IGHV-UM remained an independent predictor of PFS (HR=8.63, 95% CI: 1.09-68.40, P=0.042). Sixteen patients with IGHV-M and lacking del (17p) or CK had a median PFS of 123 (58,123) months and a 5-year PFS rate of 70.7% (95% CI: 49.7-99.1% ), reaching a plateau after 5 years with no recurrences by 10 years. Common grade 3-4 adverse events included hematologic toxicity (44.1%, 30/68), infection (36.7%, 25/68), and liver dysfunction (4.4%, 3/68). Among 25 patients receiving single-agent BTK inhibitors after FCR progression, median follow-up was 45 (26, 64) months; 36% (9/25) experienced disease progression, with a median PFS time of 55 (27, 55) months. Conclusion: First-line FCR provides durable long-term benefits for patients with IGHV-M CLL without del (17p) or CK.