PD-1之后怎么办？

橙色雨丝

T028 (0163) ALLOGENEIC STEM CELL TRANSPLANTATION (Allo-SCT) FOR RELAPSED/REFRACTORY CLASSICAL HODGKIN LYMPHOMA (cHL) PATIENTS TREATED WITH NIVOLUMAB IS ASSOCIATED WITH AN UNPRECEDENTED LOW RELAPSE RATE

Luca Castagna1, Massimo Magagnoli1, Rita Mazza1, Lucia Morello1, Francesca Ricci1, Stefania Bramanti1, Barbara Sarina1, Jacopo Mariotti1, Chiara De Philippis1, Simona Sica2, Marcello Rodari3, Martina Sollini3, Margarita Kirienko3, Arturo Chiti3,4, Armando Santoro1,4,

Carmelo Carlo-Stella1,4

1Hematology, Humanitas Cancer Center, Humanitas Research Hospital, Rozzano- Milano, Italy, 2Fondazione Policlinico Agostino Gemelli IRCCS - Università Cattolica del Sacro Cuore, Roma, Italy, 3Nuclear Medicine, Humanitas Research Hospital, Rozzano-Milano, Italy, 4Department of Biomedical Sciences, Humanitas University, Rozzano-Milano, Italy

Introduction: Phase 1/2 trials using PD-1 inhibitors in relapsed/refracto- ry (r/r) cHL who failed brentuximab vedotin (BV) and autologous SCT (Auto-SCT) showed unprecedented rates of complete/partial response (CR/PR) and durable responses. However, the absence of a plateau in the PFS curves indirectly suggests that Allo-SCT may represent a consolidation therapy for patients responding to PD-1 therapy.

Methods: From Nov 2014 to Dec 2016, 37 r/r cHL enrolled in the CA209–205 and CA209–254 trials (median age, 32 years; range, 18–81) received nivolumab until CR, PR (tumor burden reduction >80%) or progressive disease (PD). At study entry, 30 patients (81%) had primary refractory disease, 32 (86%) had failed BV and 33 (89%) Auto-SCT. Results: After a median duration of nivolumab therapy of 10 months (range, 3–33), 16 cases (43%) experienced CR/PR and 21 cases (57%) PD. Fourteen of 16 responding patients were allografted. Thirteen of 21 patients in PD after Nivolumab achieved an objective response (CR or PR) after additional chemotherapy or radiotherapy and were finally allografted. Overall, 27 of 37 patients were allografted with a median follow-up of 19 months for survivors (range, 3–40). The median time from last nivolumab to Allo-SCT was 47 days (range, 23 – 372). At Allo-SCT, 18 patients (67%) were in CR, 8 (30%) in PR and 1 (3%) in PD. Donors were haploidentical sibling (n = 19), matched sibling (n = 4), or matched unrelated (n = 4). Stem cell source was bone marrow (n = 11) and peripheral blood (n = 16). Five patients died due to disease progression (n = 1) or non-relapse mortality (NRM, n = 4, including aGVHD, CMV pneumonia, heart failure, PTLD). The 2-year cumulative incidence (CI) of relapse and NRM was 3.8% and 12%, respectively. The CI of grade 2–4 and grade 3–4 acute GVHD was 46% and 10%, respectively; the 1-year CI of cGVHD was 22%. Five patients experienced macrophage activation syndrome, 13 cytokine release syndrome, 1 posterior reversible encephalopathy syndrome. The 2-year OS and PFS were 74% (95% CI, 45 to 89) and 75% (95% CI, 46 to 90), respectively.

Conclusions: Allo-SCT after nivolumab or nivolumab plus chemotherapy has a manageable toxicity and is associated with an unprecedented low relapse incidence. PD-1 inhibitors represent a paradigm shift in the treatment of relapsed and refractory cHL

保佑吧

霍奇金混合细胞型四疗后cr做了15次放疗！之后普通ct检查显示纵隔最大1厘米，然后医生又建议再做两个疗程化疗！说如果还没消干净的话要cart！请问二期的霍奇金，治疗效果都很好有必要上cart 吗？
霍奇金淋巴瘤真的能达到治疗的一点残留都没有吗

橙色雨丝

前几天，关于PD-1是否能够治愈复发难治经典霍奇金有过一些讨论。到目前为止，这个问题还没有明确答案，不过，在现有的PFS曲线上，还未能发现明显的平台，说明复发/进展的风险是时刻存在的，急需找到一个彻底的解决方案。意大利人做的这项研究具有一定的提示意义：37位复发难治的经典霍奇金患者，其中86%经Brentuximab Vedotin（SGN-35）治疗无效或复发，89%经自体干细胞移植后复发，然后接受了中位10个月的PD-1单抗Opdivo的治疗，43%的患者获得CR/PR，57%是PD，PD的患者接受了进一步的化疗或放疗，最后，一共有27位患者具备了移植的条件而进行了异体干细胞移植，其中包括18位CR、8位PR和1位PD患者。从最后一次接受Opdivo治疗到异体移植的中位时间是47天。在19个月的中位随访期内，1位患者死于疾病进展，4位患者死于移植相关原因（感染，aGVHD等），2年累计复发率为3.8%，移植相关死亡率为12%，2年总生存率和无进展生存率分别为74%和75%。研究的结论是：复发难治的经典霍奇金在PD-1单抗或PD-1单抗+化疗后进行异体干细胞移植的毒性可控并取得了前所未有的超低复发率。

forestliu2014

谢谢你的信息分享！希望我们的医生也能关注这一研究。

普殷

还是异基因有效。   ASCT后复发的患者，果然应该积极考虑HSCT，就目前来看PD-1还是只能缓解，虽然说PD-1可能增加GVHD的风险，但是都到CD30无效的最后一步了，也是没办法的办法

zhangqingbinsc

一个霍奇金，最终搞得跟白血病一个量级。
个别倒霉蛋只能骂骂天。
但也要吐槽一下某些神医。
水平达标的医生，至少在自体复发后进入未知领域。
神医们abvd无效后就可以进入未知领域。
比如abvd换chop未cr结疗。
这是省级肿瘤医院的杰作。
县级乙等医院化疗科大夫比着指南出方案也不至于这样吧。
能力问题？态度问题？
这样的可都是有执照的~

境随心转

这个方法在国内也不是那么现实。有相关报道说pd1+HSCT会增加排异反应，如何安全序贯也是问题。另外，霍奇金的年轻患者大部分都是独生子女一代，配型困难。

Ciaoii

zhangqingbinsc 发表于 2018-11-20 16:03
一个霍奇金，最终搞得跟白血病一个量级。
个别倒霉蛋只能骂骂天。
但也要吐槽一下某些神医。

你说的山东省肿瘤医院吧，哈哈

GU.GL

境随心转 发表于 2018-11-20 17:43
这个方法在国内也不是那么现实。有相关报道说pd1+HSCT会增加排异反应，如何安全序贯也是问题。另外，霍奇金 ...

同意

120853588

Ciaoii 发表于 2018-11-20 18:37
你说的山东省肿瘤医院吧，哈哈

湖北省肿瘤也一样

小刘老师

看了雨丝老师这篇帖子，突然间感觉比较迷茫，我们现在是pd-1联合eshap方案，如果达到cr了，是否必须进行移植啊？

zhangsan

120853588 发表于 2019-2-18 05:14
湖北省肿瘤也一样

差点转去湖北省肿瘤医院了，挂了湖北肿瘤一个医生的号，看见myc30%  bcl2+ bcl6+直接来了句3打击，吓得我不敢去了

小刘老师

zhangsan 发表于 2019-2-18 13:03
差点转去湖北省肿瘤医院了，挂了湖北肿瘤一个医生的号，看见myc30%  bcl2+ bcl6+直接来了句3打击，吓得我 ...

我媳妇纵膈里的淋巴瘤跟心脏差不多大，我们当地市医院的大夫看了CT片子以后非说我媳妇心脏长在中间！！

橙色雨丝

保佑吧 发表于 2019-2-19 11:22
霍奇金混合细胞型四疗后cr做了15次放疗！之后普通ct检查显示纵隔最大1厘米，然后医生又建议再做两个疗程化 ...

经典霍奇金做CAR-T目前还没有长期缓解的先例。

保佑吧

橙色雨丝 发表于 2019-2-19 13:24
经典霍奇金做CAR-T目前还没有长期缓解的先例。

谢谢