Lee Hun Ju, Ramchandren Rod, Friedman Judah, Melear Jason, Flinn Ian W, Burke John M, Linhares Yuliya, Gonzales Paul, Peterson Matthew, Raval Mihir, Chintapatla Rangaswamy, Feldman Tatyana A, Yimer Habte, Islas-Ohlmayer Miguel, Patel Ameet, Metheny Leland, Dean Asad, Rana Vishal, Gandhi Mitul D, Renshaw John, Ho Linda, Fanale Michelle A, Guo Wenchuan, Yasenchak Christopher A
MD Anderson Cancer Center, Houston, TX.
University of Tennessee Medical Center, Knoxville, TN.
Blood. 2025 Jan 16;145(3):290-299. doi: 10.1182/blood.2024024681.
Treatment options for stage I/II bulky and advanced-stage disease have recently extensively changed. For decades in North America, ABVD (doxorubicin hydrochloride [Adriamycin], bleomycin sulfate, vinblastine sulfate, and dacarbazine) has been a frontline standard-of-care option for patients with advanced classical Hodgkin lymphoma (cHL). Recent data on combining brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine demonstrated improved overall survival compared with ABVD but increased adverse events (AEs). We hypothesized that replacing vinblastine with nivolumab (brentuximab vedotin and nivolumab [AN] + doxorubicin and dacarbazine [AD]; AN+AD) may improve efficacy and safety. This phase 2, open-label multipart, multicenter study enrolled patients with treatment-naive stage II bulky or III/IV cHL. Patients received ≤6 cycles of AN+AD; granulocyte-colony stimulating factor (G-CSF) prophylaxis was optional, per institutional guidelines. At the time of planned analysis (N = 57), complete response (CR) and objective response rates were 88% (95% confidence interval [CI], 76.3-94.9) and 93% (95% CI, 83.0-98.1), respectively. With a median follow-up of 24.2 months (95% CI, 23.4-26.9), the 2-year progression-free survival rate was 88% (95% CI, 75.7-94.6); 88% (95% CI, 75.7-94.6) had a response lasting >2 years. Most common grade ≥3 treatment-related AEs were alanine aminotransferase increased (11%) and neutropenia (9%); 44% had treatment-related peripheral sensory neuropathy (grade 1/2, 40%; grade 3, 4%). No febrile neutropenia occurred; 49% received G-CSF prophylaxis. AN+AD led to a high CR rate and favorable safety profile. Further evaluation of programmed death receptor 1 inhibitor and CD30 antibody-drug conjugate combination regimens in frontline advanced-stage cHL is warranted. This trial was registered at www.clinicaltrials.gov as #NCT03646123 and www.clinicaltrialsregister.eu as #EudraCT 2020-004027-17.
I/II期大包块及晚期疾病的治疗方案最近发生了广泛变化。在北美数十年来，阿霉素、博来霉素、长春花碱和达卡巴嗪（ABVD方案）一直是晚期经典型霍奇金淋巴瘤（cHL）患者的一线标准治疗方案。近期关于将维布妥昔单抗、阿霉素、长春花碱和达卡巴嗪联合应用的数据显示，与ABVD方案相比，总生存期有所改善，但不良事件（AE）增加。我们推测，用纳武利尤单抗替代长春花碱（维布妥昔单抗和纳武利尤单抗[AN]+阿霉素和达卡巴嗪[AD]；AN+AD方案）可能会提高疗效和安全性。这项2期、开放标签、多部分、多中心研究纳入了初治的II期大包块或III/IV期cHL患者。患者接受≤6个周期的AN+AD方案治疗；根据机构指南，可选择使用粒细胞集落刺激因子（G-CSF）进行预防。在计划分析时（N = 57），完全缓解（CR）率和客观缓解率分别为88%（95%置信区间[CI]，76.3-94.9）和93%（95%CI，83.0-98.1）。中位随访24.2个月（95%CI，23.4-26.9），2年无进展生存率为88%（95%CI，75.7-94.6）；88%（95%CI，75.7-94.6）的患者缓解持续时间>2年。最常见的≥3级治疗相关AE为丙氨酸转氨酶升高（11%）和中性粒细胞减少（9%）；44%的患者出现治疗相关的周围感觉神经病变（1/2级，40%；3级，4%）。未发生发热性中性粒细胞减少；49%的患者接受了G-CSF预防。AN+AD方案导致高CR率和良好的安全性。有必要对一线晚期cHL中程序性死亡受体1抑制剂和CD30抗体-药物偶联物联合方案进行进一步评估。本试验在www.clinicaltrials.gov注册为#NCT03646123，在www.clinicaltrialsregister.eu注册为#EudraCT 2020-004027-17。
