Mei Matthew G, Lee Hun Ju, Palmer Joycelynne M, Chen Robert, Tsai Ni-Chun, Chen Lu, McBride Kathryn, Smith D Lynne, Melgar Ivana, Song Joo Y, Bonjoc Kimberley-Jane, Armenian Saro, Nwangwu Mary, Lee Peter P, Zain Jasmine, Nikolaenko Liana, Popplewell Leslie, Nademanee Auayporn, Chaudhry Ammar, Rosen Steven, Kwak Larry, Forman Stephen J, Herrera Alex F
Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA.
Department of Lymphoma and Myeloma, MD Anderson Cancer Center, Houston, TX; and.
Blood. 2022 Jun 23;139(25):3605-3616. doi: 10.1182/blood.2022015423.
This phase 2 trial evaluated PET-adapted nivolumab alone or in combination with ifosfamide, carboplatin, and etoposide (NICE) as first salvage therapy and bridge to autologous hematopoietic cell transplantation (AHCT) in relapsed/refractory (RR) classical Hodgkin lymphoma (cHL). Patients with RR cHL received 240 mg nivolumab every 2 weeks for up to 6 cycles (C). Patients in complete response (CR) after C6 proceeded to AHCT, whereas patients with progressive disease at any point or not in CR after C6 received NICE for 2 cycles. The primary endpoint was CR rate per the 2014 Lugano classification at completion of protocol therapy. Forty-three patients were evaluable for toxicity; 42 were evaluable for response. Thirty-four patients received nivolumab alone, and 9 patients received nivolumab+NICE. No unexpected toxicities were observed after nivolumab or NICE. After nivolumab, the overall response rate (ORR) was 81%, and the CR rate was 71%. Among 9 patients who received NICE, all responded, with 8 (89%) achieving CR. At the end of protocol therapy, the ORR and CR rates were 93% and 91%. Thirty-three patients were bridged directly to AHCT, including 26 after Nivo alone. The 2-year progression-free survival (PFS) and overall survival in all treated patients (n = 43) were 72% and 95%, respectively. Among 33 patients who bridged directly to AHCT, the 2-year PFS was 94% (95% CI: 78-98). PET-adapted sequential salvage therapy with nivolumab/nivolumab+NICE was well tolerated and effective, resulting in a high CR rate and bridging most patients to AHCT without chemotherapy. This trial was registered at www.clinicaltrials.gov #NCT03016871.
这项2期试验评估了经PET调整的纳武利尤单抗单药治疗或联合异环磷酰胺、卡铂和依托泊苷(NICE方案)作为复发/难治性(RR)经典型霍奇金淋巴瘤(cHL)的一线挽救治疗及自体造血细胞移植(AHCT)的桥梁治疗效果。RR cHL患者每2周接受240 mg纳武利尤单抗治疗,最多6个周期(C)。C6治疗后达到完全缓解(CR)的患者继续接受AHCT,而在任何时间点出现疾病进展或C6治疗后未达到CR的患者接受2个周期的NICE方案治疗。主要终点是按照2014年卢加诺分类标准在方案治疗结束时的CR率。43例患者可评估毒性;42例可评估疗效。34例患者接受纳武利尤单抗单药治疗,9例患者接受纳武利尤单抗+NICE方案治疗。在使用纳武利尤单抗或NICE方案后未观察到意外毒性。使用纳武利尤单抗后,总缓解率(ORR)为81%,CR率为71%。在接受NICE方案治疗的9例患者中,所有患者均有反应,8例(89%)达到CR。在方案治疗结束时,ORR和CR率分别为93%和91%。33例患者直接接受AHCT,其中26例在仅接受纳武利尤单抗治疗后接受AHCT。所有接受治疗的患者(n = 43)的2年无进展生存期(PFS)和总生存期分别为72%和95%。在直接接受AHCT的33例患者中,2年PFS为94%(95%CI:78-98)。经PET调整的纳武利尤单抗/纳武利尤单抗+NICE序贯挽救治疗耐受性良好且有效,导致高CR率,并使大多数患者无需化疗即可接受AHCT。本试验已在www.clinicaltrials.gov注册,注册号为#NCT03016871。