一线伊布替尼与利妥昔单抗联合治疗的疗效及治疗中断对不适合接受治疗的慢性淋巴细胞白血病患者的影响：Gimema LLC1114研究结果

Efficacy of Front-Line Ibrutinib and Rituximab Combination and the Impact of Treatment Discontinuation in Unfit Patients with Chronic Lymphocytic Leukemia: Results of the Gimema LLC1114 Study.

作者信息

Mauro Francesca Romana, Paoloni Francesca, Molica Stefano, Reda Gianluigi, Trentin Livio, Sportoletti Paolo, Marchetti Monia, Pietrasanta Daniela, Marasca Roberto, Gaidano Gianluca, Coscia Marta, Stelitano Caterina, Mannina Donato, Di Renzo Nicola, Ilariucci Fiorella, Liberati Anna Marina, Orsucci Lorella, Re Francesca, Tani Monica, Musuraca Gerardo, Gottardi Daniela, Zinzani Pier Luigi, Gozzetti Alessandro, Molinari Annalia, Gentile Massimo, Chiarenza Annalisa, Laurenti Luca, Varettoni Marzia, Ibatici Adalberto, Murru Roberta, Ruocco Valeria, Del Giudice Ilaria, De Propris Maria Stefania, Della Starza Irene, Raponi Sara, Nanni Mauro, Fazi Paola, Neri Antonino, Guarini Anna, Rigolin Gian Matteo, Piciocchi Alfonso, Cuneo Antonio, Foà Robin

机构信息

Hematology, Department of Translational and Precision Medicine, Sapienza University, Via Benevento 6, 00161 Rome, Italy.

GIMEMA Foundation, 00187 Rome, Italy.

出版信息

Cancers (Basel). 2021 Dec 31;14(1):207. doi: 10.3390/cancers14010207.

DOI:10.3390/cancers14010207

PMID:35008372

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8750939/

Abstract

The GIMEMA group investigated the efficacy, safety, and rates of discontinuations of the ibrutinib and rituximab regimen in previously untreated and unfit patients with chronic lymphocytic leukemia (CLL). Treatment consisted of ibrutinib, 420 mg daily, and until disease progression, and rituximab (375 mg/sqm, given weekly on week 1-4 of month 1 and day 1 of months 2-6). This study included 146 patients with a median age of 73 years, with IGHV unmutated in 56.9% and 53 disrupted in 22.2%. The OR, CR, and 48-month PFS rates were 87%, 22.6%, and 77%, respectively. Responses with undetectable MRD were observed in 6.2% of all patients and 27% of CR patients. 53 disruption (HR 2.47; = 0.03) and B-symptoms (HR 2.91; = 0.02) showed a significant and independent impact on PFS. The 48-month cumulative rates of treatment discontinuations due to disease progression (DP) or adverse events (AEs) were 5.6% and 29.1%, respectively. AEs leading more frequently to treatment discontinuation were atrial fibrillation in 8% of patients, infections in 8%, and non-skin cancers in 6%. Discontinuation rates due to AEs were higher in male patients (HR: 0.46; = 0.05), patients aged ≥70 years (HR 5.43, = 0.0017), and were managed at centers that enrolled <5 patients (HR 5.1, = 0.04). Patients who discontinued ibrutinib due to an AE showed a 24-month next treatment-free survival rate of 63%. In conclusion, ibrutinib and rituximab combination was an effective front-line treatment with sustained disease control in more than half of unfit patients with CLL. Careful monitoring is recommended to prevent and manage AEs in this patient population.

摘要

GIMEMA研究小组调查了依鲁替尼和利妥昔单抗方案在既往未经治疗且身体状况不佳的慢性淋巴细胞白血病（CLL）患者中的疗效、安全性及停药率。治疗方案为每日口服依鲁替尼420 mg，直至疾病进展，以及利妥昔单抗（375 mg/m²，在第1个月的第1 - 4周每周给药，第2 - 6个月的第1天给药）。该研究纳入了146例患者，中位年龄为73岁，其中56.9%的患者IGHV未突变，22.2%的患者有53号染色体缺失。总体缓解率（OR）、完全缓解率（CR）和48个月无进展生存率（PFS）分别为87%、22.6%和77%。所有患者中有6.2%、CR患者中有27%达到微小残留病（MRD）不可检测的缓解。53号染色体缺失（风险比[HR] 2.47；P = 0.03）和B症状（HR 2.91；P = 0.02）对PFS有显著且独立的影响。因疾病进展（DP）或不良事件（AE）导致的48个月累积停药率分别为5.6%和29.1%。导致停药更频繁的AE包括8%的患者出现心房颤动、8%的患者出现感染以及6%的患者出现非皮肤癌。男性患者（HR：0.46；P = 0.05）、年龄≥70岁的患者（HR 5.43，P = 0.0017）以及在入组患者<5例的中心接受治疗的患者（HR 5.1，P = 0.04）因AE导致的停药率更高。因AE停用依鲁替尼的患者24个月的下次无治疗生存期率为63%。总之，依鲁替尼和利妥昔单抗联合方案是一种有效的一线治疗方案，可使超过半数身体状况不佳的CLL患者实现持续疾病控制。建议对该患者群体进行密切监测，以预防和管理AE。