Background 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 and methods 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. Results 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. Conclusions 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. ClinicalTrials.gov number NCT01685008.

中文翻译：

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II19a期CD19抗体MOR208在复发或难治性B细胞非霍奇金淋巴瘤患者中的研究。

背景这项为期IIa的两阶段研究研究了Fc改造的人源化CD19抗体MOR208对复发或难治性（RR）B细胞非霍奇金淋巴瘤（NHL）患者的抗肿瘤活性和安全性。CD19在B淋巴细胞谱系中广泛表达，包括在B细胞恶性肿瘤中表达，但在血液学干细胞中不表达。患者和方法年龄≥18岁且在接受含利妥昔单抗治疗的≥1次治疗后RR NHL进展的患者纳入亚型特异性队列：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MOR208，每周一次静脉内12 mg / kg，持续8周。疾病至少稳定的患者可以继续治疗另外4周。那些在12周后部分或完全缓解的患者可以接受延长的MOR208治疗（12 mg / kg，每月一次或每两周一次）直至进展。主要终点是总体缓解率。结果共纳入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队列中观察到了反应（分别为26％，29％和27％）。在5/9有反应的DLBCL，4/9有FL和2/3有其他iNHL的患者中，他们持续≥12个月。9名患者的反应仍在进行中（5例> 26个月）。利妥昔单抗难治性疾病患者的反应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）是与输注相关的反应（占12％）和中性粒细胞减少（占12％）。一名患者经历了4级输注相关反应，八名患者（9％）经历了3/4级中性粒细胞减少症。没有报道与治疗有关的死亡。结论MOR208单一疗法在RR DLBCL和RR FL患者（包括利妥昔单抗难治性肿瘤患者）中显示出令人鼓舞的临床活性。这些功效数据和良好的安全性支持了在RR DLBCL的II / III期联合治疗试验中对MOR208的进一步研究。ClinicalTrials.gov编号NCT01685008。这些功效数据和良好的安全性支持了在RR DLBCL的II / III期联合治疗试验中对MOR208的进一步研究。ClinicalTrials.gov编号NCT01685008。这些功效数据和良好的安全性支持了在RR DLBCL的II / III期联合治疗试验中对MOR208的进一步研究。ClinicalTrials.gov编号NCT01685008。