帕沙利西联合奥比妥珠单抗和苯达莫司汀治疗复发或难治滤泡性淋巴瘤患者的安全性和有效性(CITADEL-102):1期研究

IF 3.3 4区 医学 Q2 HEMATOLOGY
Mehdi Hamadani, Morton Coleman, Ralph Boccia, Juraj Duras, Martin Hutchings, Pier Luigi Zinzani, Raul Cordoba, Mariana Bastos Oreiro, Vanessa Williams, Huiqing Liu, Michael Stouffs, Peter Langmuir, Juan-Manuel Sancho
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引用次数: 0

摘要

Parsaclisib是一种强效、高选择性PI3Kδ抑制剂,在复发或难治性(R/R)滤泡性淋巴瘤(FL)的2期研究中,单药治疗已显示出临床疗效。CITADEL-102(NCT03039114)是一项多中心1期研究,评估了帕沙利西联合奥比妥珠单抗和苯达莫司汀治疗R/R FL患者的疗效。患者年龄≥18岁,组织学确诊并记录CD20阳性FL,既往接受过含利妥昔单抗的治疗方案,但仍为R/R。第一部分(安全性试验)确定了帕沙利布与奥比妥珠单抗和苯达莫司汀标准剂量方案的最大耐受剂量。第二部分(剂量扩展)为开放标签、单组设计,评估帕沙利西联合疗法的安全性、耐受性(主要终点)和疗效(次要终点)。CITADEL-102共招募了26名患者,所有患者都接受了帕沙利西20毫克、每天一次、为期8周的治疗,之后每周一次、每次20毫克,与奥比妥珠单抗和苯达莫司汀联合治疗。安全运行期有一名患者出现了剂量限制性毒性,即4级QT间期延长,考虑与帕沙利西有关。8名患者(30.8%)因以下治疗突发不良事件(TEAEs)停止治疗:结肠炎(2例[7.7%])、丙氨酸氨基转移酶和天冬氨酸氨基转移酶升高(均为1例患者[3.8%])、中性粒细胞减少、血小板减少、QT延长、扁桃体癌和斑丘疹(各1例[3.8%])。最常见的 TEAEs 为发热(53.8%)、中性粒细胞减少(50.0%)和腹泻(46.2%)。23名患者(88.5%)出现了3级或4级TEAE;最常见的是中性粒细胞减少症(34.6%)、发热性中性粒细胞减少症(23.1%)和血小板减少症(19.2%)。17名患者(65.4%)完全应答,3名患者(11.5%)部分应答,客观应答率为76.9%。总体而言,CITADEL-102的研究结果表明,帕沙利西与奥比妥珠单抗和苯达莫司汀的联合用药不会导致意外的安全事件,几乎没有证据表明存在协同毒性,而且对既往接受过含利妥昔单抗方案治疗后病情进展的R/R FL患者具有初步疗效。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Safety and efficacy of parsaclisib in combination with obinutuzumab and bendamustine in patients with relapsed or refractory follicular lymphoma (CITADEL-102): A phase 1 study

Safety and efficacy of parsaclisib in combination with obinutuzumab and bendamustine in patients with relapsed or refractory follicular lymphoma (CITADEL-102): A phase 1 study

Parsaclisib is a potent and highly selective PI3Kδ inhibitor that has shown clinical benefit with monotherapy in a phase 2 study in relapsed or refractory (R/R) follicular lymphoma (FL). CITADEL-102 (NCT03039114), a phase 1, multicenter study, assessed the efficacy of parsaclisib in combination with obinutuzumab and bendamustine in patients with R/R FL. Patients were ≥18 years of age with histologically confirmed and documented CD20-positive FL, and R/R to previous rituximab-containing treatment regimens. Part one (safety run-in) determined the maximum tolerated dose of parsaclisib in combination with standard dosage regimens of obinutuzumab and bendamustine. Part two (dose expansion) was an open-label, single-group design evaluating safety, tolerability (primary endpoint), and efficacy (secondary endpoint) of parsaclisib combination therapy. Twenty-six patients were enrolled in CITADEL-102 and all patients received parsaclisib 20 mg once daily for 8 weeks, followed by 20 mg once weekly thereafter, in combination with obinutuzumab and bendamustine. One patient in safety run-in experienced a dose-limiting toxicity of grade 4 QT interval prolongation that was considered related to parsaclisib. Eight patients (30.8%) discontinued treatment due to treatment-emergent adverse events (TEAEs) of colitis (2 [7.7%]), alanine aminotransferase and aspartate aminotransferase increase (both in one patient [3.8%]), neutropenia, thrombocytopenia, QT prolongation, tonsil cancer, and maculopapular rash (each 1 [3.8%]). The most common reported TEAEs were pyrexia (53.8%), neutropenia (50.0%), and diarrhea (46.2%). Twenty-three patients (88.5%) experienced grade 3 or 4 TEAEs; the most common were neutropenia (34.6%), febrile neutropenia (23.1%), and thrombocytopenia (19.2%). Seventeen patients (65.4%) had a complete response and 3 patients (11.5%) had a partial response, for an objective response rate of 76.9%. Overall, results from CITADEL-102 suggest that the combination of parsaclisib with obinutuzumab and bendamustine did not result in unexpected safety events, with little evidence of synergistic toxicity, and demonstrated preliminary efficacy in patients with R/R FL who progressed following prior rituximab-containing regimens.

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来源期刊
Hematological Oncology
Hematological Oncology 医学-血液学
CiteScore
4.20
自引率
6.10%
发文量
147
审稿时长
>12 weeks
期刊介绍: Hematological Oncology considers for publication articles dealing with experimental and clinical aspects of neoplastic diseases of the hemopoietic and lymphoid systems and relevant related matters. Translational studies applying basic science to clinical issues are particularly welcomed. Manuscripts dealing with the following areas are encouraged: -Clinical practice and management of hematological neoplasia, including: acute and chronic leukemias, malignant lymphomas, myeloproliferative disorders -Diagnostic investigations, including imaging and laboratory assays -Epidemiology, pathology and pathobiology of hematological neoplasia of hematological diseases -Therapeutic issues including Phase 1, 2 or 3 trials as well as allogeneic and autologous stem cell transplantation studies -Aspects of the cell biology, molecular biology, molecular genetics and cytogenetics of normal or diseased hematopoeisis and lymphopoiesis, including stem cells and cytokines and other regulatory systems. Concise, topical review material is welcomed, especially if it makes new concepts and ideas accessible to a wider community. Proposals for review material may be discussed with the Editor-in-Chief. Collections of case material and case reports will be considered only if they have broader scientific or clinical relevance.
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