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    • Phase Ib study of avadomide (CC‐122) in combination with rituximab in patients with relapsed/refractory diffuse large B‐cell lymphoma and follicular lymphoma

    eJHaem（2022）

    Department of Lymphoma and Myeloma Division of Cancer Medicine MD Anderson Cancer Center The University of Texas Houston Texas USA | Division of Medical Oncology and Hematology Princess Margaret Cancer Centre University of Toronto Toronto Ontario Canada | H. Lee Moffitt Cancer Center and Research Institute Tampa Florida USA | Institut Bergonié Bordeaux Cedex France | Mayo Clinic Rochester Minnesota USA | Department of Biomedical Sciences Pieve Emanuele Milan Humanitas University Italy ‐IRCCS Humanitas Research Hospital‐ Humanitas Cancer Center Rozzano Milan Italy | Sarah Cannon Research Institute Nashville Tennessee USA | SC Ematologia ASOU Città della Salute e della Scienza di Torino Turin Italy | Division of Hematology and Oncology University of Wisconsin Madison Wisconsin USA | IRCCS Istituto Nazionale dei Tumori University of Milano Milano Italy | Yale Cancer Center New Haven Connecticut USA | Rocky Mountain Cancer Centers The US Oncology Network Boulder Colorado USA | Illinois Cancer Specialists The US Oncology Network Niles Illinois USA | Cancer Center of Santa Barbara Santa Barbara California USA | Cross Cancer Institute Edmonton Alberta Canada | Bristol Myers Squibb Princeton New Jersey USA | Centre for Innovation and Translational Research Europe (CITRE) Bristol‐Myers Squibb Company Seville Spain | Institut Gustave Roussy Villejuif France

    Cited 7|Views27
    Abstract
    Abstract The multicenter, phase Ib CC‐122‐DLBCL‐001 dose‐expansion study (NCT02031419) explored the cereblon E3 ligase modulator (CELMoD) agent avadomide (CC‐122) plus rituximab in patients with relapsed/refractory (R/R) diffuse large B‐cell lymphoma (DLBCL) or follicular lymphoma (FL). Patients received avadomide 3 mg/day 5 days on/2 days off plus rituximab 375 mg/m2 on day 8 of cycle 1, day 1 of cycles 2 through 6, and day 1 of every third subsequent cycle for 2 years. Primary endpoints were safety and tolerability; preliminary efficacy was a secondary endpoint. A total of 68 patients were enrolled (DLBCL [n = 27], FL [n = 41; 31 lenalidomide‐naïve, 10 lenalidomide‐treated]). Median age was 62 years (range, 33–84 years), and patients had received a median of 3 (range, 1–8) prior regimens. Among patients with DLBCL, 66.7% had primary refractory disease (partial response or less to initial therapy). Among patients with FL, 65.9% were rituximab‐refractory at study entry and 10.0% were lenalidomide‐refractory. The most common any‐grade avadomide‐related adverse events (AEs) were neutropenia (63.2%), infections/infestations (23.5%), fatigue (22.1%), and diarrhea (19.1%). The most common grade 3/4 avadomide‐related AEs were neutropenia (55.9%) infections/infestations (8.8%), and febrile neutropenia (7.4%). In patients with DLBCL, overall response rate (ORR) was 40.7% and median duration of response (mDOR) was 8.0 months. In patients with FL, ORR was 80.5% and mDOR was 27.6 months; response rates were similar in lenalidomide‐naïve and ‐treated patients. Avadomide plus rituximab was well tolerated, and preliminary antitumor activity was observed in patients with R/R DLBCL and FL, including subgroups with typically poor outcomes. These results support further investigation of novel CELMoD agents in combination with rituximab in R/R DLBCL and FL.
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    avadomide,CELMoD,diffuse large B‐cell lymphoma,follicular lymphoma
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    【要点】：本研究探讨了Cereblon E3连接酶调节剂Avadomide (CC-122)与利妥昔单抗联合治疗复发/难治性大B细胞淋巴瘤和滤泡性淋巴瘤的安全性和有效性，创新点在于观察到了CC-122与rituximab联合治疗的初步抗肿瘤活性。
    

    【方法】：采用多中心、Ib期临床试验设计，纳入了68例复发/难治性大B细胞淋巴瘤或滤泡性淋巴瘤患者，给予CC-122 3 mg/d连续5天，每2天休息1天，联合rituximab 375 mg/m²在第1周期第8天、第2-6周期第1天及之后每3个周期第1天给药，共2年。主要终点是安全性及耐受性，次要终点是初步疗效。
    

    【实验】：68例患者入组，其中弥漫大B细胞淋巴瘤27例，滤泡性淋巴瘤41例（31例lenalidomide初治，10例lenalidomide经治）。中位年龄62岁（范围33-84岁），患者中位接受过3个（范围1-8个）前期治疗方案。DLBCL患者中66.7%为原发性难治性疾病（对初始治疗部分响应或更差），FL患者中65.9%在研究开始时对rituximab难治性，10.0%对lenalidomide难治性。最常见的任何级别的CC-122相关不良事件为中性粒细胞减少（63.2%）、感染/寄生虫病（23.5%）、疲劳（22.1%）和腹泻（19.1%）。最常见的3/4级CC-122相关不良事件为中性粒细胞减少（55.9%）、感染/寄生虫病（8.8%）和发热性中性粒细胞减少（7.4%）。在DLBCL患者中，总反应率（ORR）为40.7%，中位反应持续时间（mDOR）为8.0个月。在FL患者中，ORR为80.5%，mDOR为27.6个月；在lenalidomide初治和经治患者中，反应率相似。CC-122与rituximab联合治疗耐受性良好，并在R/R DLBCL和FL患者中观察到初步抗肿瘤活性，包括通常预后不佳的亚组患者。研究结果支持进一步探索CC-122与rituximab联合用于治疗R/R DLBCL和FL的临床试验。