Time to hematologic recovery predicts survival in chronic lymphocytic leukemia patients treated with fludarabin, cyclophosphamide and rituximab – 11 years of real‐world experience

Introduction: Chemotherapy-free regimens are frequently the first choice in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) treatment. Despite some concerns about short and long-term toxicity, chemotherapy is still a highly valuable option in a specific subset of patients. We wanted to assess efficacy, overall and progression free survival (OS and PFS), short and long-term toxicity and predictors of response in the real-life setting. Methods: Unicentric, retrospective study of CLL/SLL patients treated with fludarabin, cyclophosphamide, rituximab (FCR) from July 2008 until April 2019. Results: Sixty-nine patients were included, 74% were male, median age of 58 year (IQR 50-63). Seventy-eight percent were treated in first line setting, 22% had relapsed/refractory (R/R) disease. Before treatment, FISH analysis was performed in 67 patients: 4.5% had (del)17p, 14.9% had del(11q), 37.3% had (del)13q, 28.4% had triss12 and 29.9% had normal cytogenetic analysis. We found 2/45 patients with TP53 mutation and 19/39 patients had mutated IgHV. Complete response (CR) was reached in 41.8%, CR with incomplete marrow recovery in 34.3%, partial response in 13.4%, stable and progressive disease in 3% and 7.5%, respectively. Minimal residual disease (MRD) was negative in 19/33 patients. Median follow-up of 59.6 months, 1st line median PFS of 55.3 months and median OS not reached, with 80.2% of patients alive at median follow up time. On the R/R setting, median PFS and OS were 41.5 and 58.3 months respectively. Negative MRD had a positive impact on survival (median PFS not reached vs. 31.3 M, p = 0.015), as well as cytogenetic analysis (p = 0.003). Half of the patients received 6 cycles and more than 75% received at least 4 cycles. Dose reduction was needed in 18% of the patients, and 36% had some delay in treatment schedule. Hematologic toxicity grade ≥3 was found in 62%: anaemia 4.3%, neutropenia 49%, thrombocytopenia 24.6%. Nearly half had complete hematologic recovery (49.7%) with median time to recovery of 124 days. Of note, PFS was longer in patients who took more than 124 days for hematologic recovery (median PFS 110.9 vs 42.7 months, p < 0.001; Fig 1). Time to hematologic recovery (HR) predicts progression free survival Infeccious adverse events grade ≥3 were found in 7.5% of patients, and 17.4% of opportunistic infections (epstein-barr, herpes zoster, P.jiroveci). Second neoplasms were found in 13% of patients: 2 acute leukemias, 3 adenocarcinomas and 4 skin neoplasms. There were 20 fatalities: 9 for progressive disease (median time to death 49 months), 3 for infectious adverse events (17-20 days after treatment), 3 for 2nd neoplasms and 5 patients for non-related causes. Conclusions: In the real-world setting with a long follow up time, FRC attained 76% of CR in 1st line therapy, with long lasting remissions and an acceptable toxicity profile. Cytogenetic analysis, negative MRD and, interestingly, longer time to hematologic recovery had a positive impact in PFS. EA – previously submitted to regional or national meetings (up to 1000 attendees). Keywords: Diagnostic and Prognostic Biomarkers, Late Effects in Lymphoma Survivors, Chronic Lymphocytic Leukemia (CLL) No conflicts of interests pertinent to the abstract.