Brentuximab vedotin in relapsed/refractory Hodgkin lymphoma. The Hellenic experience

This retrospective study aimed to describe the Hellenic experience on the use of brentuximab vedotin (BV) in relapsed/refractory (R/R) Hodgkin lymphoma (HL) given within its indication. From June 2011 to April 2015, ninety‐five patients with R/R HL, who received BV in 20 centers from Greece, were analyzed. Their median age was 33 years, and 62% were males. Sixty‐seven patients received BV after autologous stem cell transplantation failure, whereas 28 patients were treated with BV without a prior autologous stem cell transplantation, due to advanced age/comorbidities or chemorefractory disease. The median number of prior treatments was 4 and 44% of the patients were refractory to their most recent therapy. The median number of BV cycles was 8 (range, 2‐16), and the median time to best response was the fourth cycle. Fifty‐seven patients achieved an objective response: twenty‐two (23%), a complete response (CR), and 35 patients (37%), a partial, for an overall response rate of 60%. Twelve patients (13%) had stable disease, and the remaining twenty‐six (27%) had progressive disease as their best response. At a median follow‐up of 11.5 months, median progression‐free survival and overall survival were 8 and 26.5 months, respectively. Multivariate analysis showed that chemosensitivity to treatment administered before BV was associated with a significantly increased probability of achieving response to BV (P = .005). Bulky disease (P = .01) and response to BV (P <.001) were significant for progression‐free survival, while refractoriness to most recent treatment (P = .04), bulky disease (P = .005), and B‐symptoms (P = .001) were unfavorable factors for overall survival. Among the 22 CRs, 5 remain in CR with no further treatment after BV at a median follow‐up of 13 months. In conclusion, our data indicate that BV is an effective treatment for R/R HL patients even outside clinical trials. Whether BV can cure a fraction of patients remains to be seen.     

复发难治弥漫大B细胞淋巴瘤患者接受polatuzumab vedotin同情用药一例并文献复习

目的:探讨polatuzumab vedotin（pola）治疗复发难治弥漫大B细胞淋巴瘤（DLBCL）患者的效果和安全性。方法:回顾性分析2016年5月江苏省肿瘤医院收治的1例多次接受治疗的DLBCL患者的临床资料,并进行文献复习。结果:该患者为57岁男性,2016年5月诊断为DLBCL,从2016年6月起接受包括抗CD20单抗联合化疗、仅化疗以及嵌合抗原受体T细胞（CAR-T）等在内的四线治疗,但治疗后均复发或进展。于2019年12月起接受pola联合利妥昔单抗6个疗程治疗,治疗过程中无非预期不良反应。治疗结束后临床疗效评价为完全缓解。随访截至2021年1月,患者无进展生存时间超过13个月。结论:pola在复发难治DLBCL患者的治疗中初步显示了良好的有效性和安全性。     

靶向CD30的抗体偶联药物Brentuximab vedotin研究进展

Brentuximab vedotin(Adcetris,SGN-35)是由美国西雅图基因公司(Seattle Genetics)和日本武田公司(Takeda)合作开发的一种靶向CD30的新型抗体偶联药物。本品通过布妥昔单抗(Brentuximab)将药物定向富集于肿瘤组织,并通过抗体介导的内吞作用在靶细胞内释放弹头药物彻底杀灭肿瘤,与传统药物相比具有更高的药效和安全性。至今,美国FDA已经获批其用于3种淋巴瘤适应证的治疗;与此同时,其扩大适应证及多种联合给药的相关临床试验结果同样鼓舞人心。笔者对Brentuximab vedotin的基本信息、作用机制、药动学、药效学等进行了概述,并结合其上市后的最新临床研究状况对该类药的研发趋势进行了展望。     

Brentuximab vedotin followed by allogeneic transplantation as salvage regimen in patients with relapsed and/or refractory Hodgkin's lymphoma

Patients with relapsed or refractory Hodgkin lymphoma (RR‐HL) have poor outcomes. Brentuximab vedotin (BV), an antibody–drug conjugate comprising an anti‐CD30 antibody conjugated to the potent anti‐microtubule agent, monomethyl auristatin E, induces high tumour responses with moderate adverse effects. In a retrospective study, we describe objective response rates and subsequent allogeneic stem cell transplantation (allo‐SCT) in patients with RR‐HL treated by BV in a named patient program in two French institutions. Twenty‐four adult patients with histologically proven CD30⁺ RR‐HL treated with BV were included from July 2009 to November 2012. Response to BV treatment was evaluated after four cycles. Eleven patients were in complete response (45.8%), while five patients were in partial response (20.8%), with an overall response rate of 66.6%. Eight patients failed to respond to BV (33.3%). All of the responding patients could receive consolidation treatment after BV: three patients underwent autologous stem cell transplantation (auto‐SCT), three patients received a tandem auto‐SCT/allo‐SCT, nine patients received allo‐SCT and one patient was treated with donor lymphocyte infusion. We found no treatment‐related mortality at day 100 among the 12 patients who underwent BV following by allogeneic transplantation. With a median follow‐up of 20 months (range 10.5–43.2), none of them relapsed or died. BV followed by allo‐SCT represents an effective salvage regimen in patients with RR‐HL. Copyright © 2013 John Wiley & Sons, Ltd.     

Current advances in Hodgkin’s lymphoma

Hodgkin’s lymphoma is a highly treatable malignancy. It has high cure rates yet there are many patients who relapse or are refractory to treatment. Traditionally, treatment has been with conventional chemotherapy; however, the development of brentuximab vedotin and immune checkpoint inhibitors has revolutionized the care of Hodgkin’s lymphoma. This is a review of the current advances in the management of Hodgkin’s lymphoma and a review of ongoing clinical trials in the field.     

Results of a multicentre UK‐wide retrospective study evaluating the efficacy of brentuximab vedotin in relapsed,refractory classical Hodgkin lymphoma in the transplant naive setting

Relapsed or refractory classical Hodgkin lymphoma (cHL) is associated with a poor outcome when standard chemotherapy fails. Brentuximab vedotin (BV) is an anti‐CD30 monoclonal antibody‐drug conjugate licensed for use at relapse after autologous stem cell transplant (ASCT) or following two prior therapies in those unsuitable for ASCT. There are limited data assessing the ability of BV to enable curative SCT. We performed a UK‐wide retrospective study of 99 SCT‐naïve relapsed/refractory cHL. All had received 2 prior lines and were deemed fit for transplant but had an insufficient remission to proceed. The median age was 32 years. Most had nodular sclerosis subtype, Eastern Cooperative Oncology Group performance status 0–1 and advanced stage disease. The median progression‐free survival (PFS) was 5·6 months and median overall survival (OS) was 37·2 months. The overall response rate was 56% (29% complete response; 27% partial response). 61% reached SCT: 34% immediately post‐BV and 27% following an inadequate BV response but were salvaged and underwent deferred SCT. Patients consolidated with SCT had a superior PFS and OS to those not receiving SCT (P < 0·001). BV is an effective, non‐toxic bridge to immediate SCT in 34% and deferred SCT in 27%. 39% never reached SCT with a PFS of 3·0 months, demonstrating the unmet need to improve outcomes in those unsuitable for SCT post‐BV.