Ibrutinib plus fludarabine, cyclophosphamide and rituximab (iFCR) as initial treatment in chronic lymphocytic leukemia/ small lymphocytic leukemia with or without TP53 aberrations: A prospective real-world study in Chinese cohort

Abstract

Abstract Time-limited treatment strategies in first line treatment of chronic lymphocytic leukemia/small lymphocytic leukemia (CLL/SLL) were comprehensively explored. Thirty-four previously untreated, young fit CLL/SLL patients who initiated iFCR regimen between January 2019 and Match 2021 were included in our cohort. iFCR were administered every 28-day cycle, with a maximum of six cycles. Patients who achieved complete remission or complete remission with incomplete recovery (CR/CRi) and bone marrow (BM) undetectable minimal residual disease (uMRD) 2 years after iFCR initiation were feasible to discontinue ibrutinib maintenance. 61.8% (21/34) patients had IGHV unmutated status and 17.6% (6/34) patients had TP53 mutation and/or del(17p). CR/CRi rate was 35.3% (12/34) and BM uMRD rate was 41.2% (14/34) after three cycles of iFCR, and increased to 55.9% (19/34) after eight cycles. The best response of CR/CRi rate and BM uMRD rate were both 73.5% (25/34). With the median follow-up of 33 months, the 3-year PFS and OS rate was 80.0% and 95.5%, respectively. CR/CRi rate and BM uMRD rate was comparable between patients with IGHV mutated and unmutated status without TP53 aberrations, while all patients with TP53 aberrations failed to achieve sustainable CR/CRi or BM uMRD. The most common hematological adverse events were neutropenia (25/34, 73.5%) and thrombocytopenia (24/34, 70.6%) and the most common non-hematological adverse events were nausea (21/34, 61.8%), fatigue (16/34, 47.1%) and vomiting (15/34, 44.1%). The iFCR regimen could achieve high response rate and proportion of uMRD as initial treatment for young fit CLL/SLL patient absence of TP53 aberration with acceptable overall tolerability.