4th Department of Internal Medicine - Haematology, Faculty of Medicine in Hradec Králové, University Hospital and Charles University in Prague, Hradec Kralove, Czech Republic.
Department of Clinical Pharmacy, Hospital Pharmacy, Faculty of Medicine in Hradec Králové, University Hospital and Charles University in Prague, Hradec Kralove, Czech Republic.
Eur J Clin Invest. 2021 Apr;51(4):e13421. doi: 10.1111/eci.13421. Epub 2020 Oct 22.
High doses of corticosteroids in combination with rituximab remain an alternative in the treatment in relapsed or refractory chronic lymphocytic leukaemia (CLL) in the current era of targeted therapies. This study retrospectively evaluates the efficacy of an RCD (rituximab, cyclophosphamide and dexamethasone) regimen in the treatment of 51 patients with relapsed CLL (median age, 72 years). Unfavourable prognostic features, such as Rai stage III/IV, unmutated IGHV, del11q, TP53 mutation/deletion, complex karyotype and bulky lymphadenopathy, were frequent. The overall response or complete remission was of 57% and 7%, respectively, and the median progression-free survival (PFS) was of 12.3 months, median time to next treatment 23.1 months and median overall survival 39.2 months. Significant independent predictors of shorter PFS were TP53 deletion/mutation, advanced Rai stage and ≥2 previous lines of treatment. The incidence of neutropenia grade ≥ 3 was of 13%. Serious (CTCAE grade 3-5) infections were found in 20% of patients. Steroid-induced diabetes or diabetes decompensation occurred in 20% patients. Treatment-related adverse events resulted in RCD dose reduction in 35% of patients. In comparison with a historical R-Dex patient group, the treatment response and/or toxicity in our group was largely similar. However, the substantial differences in the baseline clinical characteristics of the groups may affect this comparison. In conclusion, the RCD regimen is an active, time-limited therapeutic strategy for elderly patients with relapsed CLL. Further, the results of our analysis indicate that the addition of cyclophosphamide to the R-Dex regimen maintains a similar efficacy, even after 50% reduction in the dexamethasone dose.
高剂量皮质类固醇联合利妥昔单抗仍然是当前靶向治疗时代复发或难治性慢性淋巴细胞白血病（CLL）的一种治疗选择。本研究回顾性评估了 RCD（利妥昔单抗、环磷酰胺和地塞米松）方案治疗 51 例复发 CLL 患者的疗效（中位年龄 72 岁）。不良预后特征如 Rai 分期 III/IV 期、未突变 IGHV、del11q、TP53 突变/缺失、复杂核型和大肿块淋巴结病较为常见。总体缓解率或完全缓解率分别为 57%和 7%，中位无进展生存期（PFS）为 12.3 个月，中位下一次治疗时间为 23.1 个月，中位总生存期为 39.2 个月。TP53 缺失/突变、晚期 Rai 分期和≥2 线治疗是 PFS 较短的显著独立预测因素。中性粒细胞减少症≥3 级的发生率为 13%。20%的患者发生严重（CTCAE 3-5 级）感染。20%的患者发生类固醇诱导的糖尿病或糖尿病失代偿。治疗相关不良事件导致 35%的患者减少 RCD 剂量。与历史 R-Dex 患者组相比，我们组的治疗反应和/或毒性基本相似。然而，两组患者的基线临床特征存在显著差异，可能会影响这种比较。总之，RCD 方案是老年复发 CLL 患者的一种积极、限时的治疗策略。此外，我们的分析结果表明，即使地塞米松剂量减少 50%，环磷酰胺加入 R-Dex 方案仍能保持相似的疗效。
