Phase IIa study of the CD19 antibody MOR208 in patients with relapsed or refractory B-cell non-Hodgkin's lymphoma.
Phase IIa study of the CD19 antibody MOR208 in patients with relapsed or refractory B-cell non-Hodgkin's lymphoma.
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DOI：
10.1093/annonc/mdy056
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发表时间：
2018-05-01
期刊：
影响因子：
--
通讯作者：
Blum KA
中科院分区：
文献类型：
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作者：
Jurczak W;Zinzani PL;Gaidano G;Goy A;Provencio M;Nagy Z;Robak T;Maddocks K;Buske C;Ambarkhane S;Winderlich M;Dirnberger-Hertweck M;Korolkiewicz R;Blum KA
这项两阶段IIa期研究调查了M0 R 208（一种Fc工程化的人源化CD 19抗体）在复发性或难治性（R-R）B细胞非霍奇金淋巴瘤（NHL）患者中的抗肿瘤活性和安全性。CD 19在B淋巴细胞谱系中广泛表达，包括在B细胞恶性肿瘤中，但不被血液干细胞表达。年龄≥18岁、既往接受≥1种含利妥昔单抗方案治疗后进展的R-R NHL患者入组亚型特异性队列：弥漫性大B细胞淋巴瘤（DLBCL）、滤泡性淋巴瘤（FL）、其他惰性（i）NHL和套细胞淋巴瘤（MCL）。治疗是M0 R 208，12 mg/kg静脉内，每周一次，持续8周。至少病情稳定的患者可继续治疗4周。在12周后具有部分或完全反应的那些可以接受延长的M0 R 208治疗（12 mg/kg，每月一次或每两周一次），直到进展。主要终点为总缓解率。入组了92例患者：DLBCL（n = 35）、FL（n = 34）、其他iNHL（n = 11）和MCL（n = 12）。在DLBCL、FL和其他iNHL队列中观察到缓解（分别为26%、29%和27%）。在5/9例DLBCL、4/9例FL和2/3例其他iNHL缓解患者中，持续时间≥12个月。9名患者的反应正在进行中（5例>26个月）。利妥昔单抗难治性疾病患者的缓解率和无进展生存时间与非难治性疾病患者相似。最常见的不良事件（任何级别）是输注相关反应（12%）和中性粒细胞减少症（12%）。1例患者发生4级输注相关反应，8例患者（9%）发生3/4级中性粒细胞减少。未报告治疗相关死亡。M0 R 208单一疗法在患有R-R DLBCL和R-R FL的患者（包括患有利妥昔单抗难治性肿瘤的患者）中显示出有希望的临床活性。这些疗效数据和有利的安全性特征支持在R-R DLBCL的II/III期联合治疗试验中对M0 R 208的进一步研究。NCT01685008。
This two-stage, phase IIa study investigated the antitumor activity and safety of MOR208, an Fc-engineered, humanized, CD19 antibody, in patients with relapsed or refractory (R-R) B-cell non-Hodgkin’s lymphoma (NHL). CD19 is broadly expressed across the B-lymphocyte lineage, including in B-cell malignancies, but not by hematological stem cells. Patients aged ≥18 years, with R-R NHL progressing after ≥1 prior rituximab-containing regimen were enrolled into subtype-specific cohorts: diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), other indolent (i)NHL and mantle cell lymphoma (MCL). Treatment was MOR208, 12 mg/kg intravenously, weekly, for 8 weeks. Patients with at least stable disease could continue treatment for an additional 4 weeks. Those with a partial or complete response after 12 weeks could receive extended MOR208 treatment (12 mg/kg, either monthly or every second week) until progression. The primary end point was overall response rate. Ninety-two patients were enrolled: DLBCL (n = 35), FL (n = 34), other iNHL (n = 11) and MCL (n = 12). Responses were observed in DLBCL, FL and other iNHL cohorts (26%, 29% and 27%, respectively). They lasted ≥12 months in 5/9 responding patients with DLBCL, 4/9 with FL and 2/3 with other iNHL. Responses in nine patients are ongoing (>26 months in five instances). Patients with rituximab refractory disease showed a similar response rate and progression-free survival time to patients with non-refractory disease. The most common adverse events (any grade) were infusion-related reactions (12%) and neutropenia (12%). One patient experienced a grade 4 infusion-related reaction and eight patients (9%) experienced grade 3/4 neutropenia. No treatment-related deaths were reported. MOR208 monotherapy demonstrated promising clinical activity in patients with R-R DLBCL and R-R FL, including in patients with rituximab refractory tumors. These efficacy data and the favorable safety profile support further investigation of MOR208 in phase II/III combination therapy trials in R-R DLBCL. NCT01685008.