Pediatrics, New York Medical College, Valhalla, New York, USA.
Epidemiology and Community Health, New York Medical College, Valhalla, NY, USA.
J Immunother Cancer. 2022 May;10(5). doi: 10.1136/jitc-2021-004445.
Cure rates for Hodgkin's lymphoma are excellent, but excess short-term and long-term morbidities from treatment remain a concern. Immunotherapy targeting both tumor antigens and the immunosuppressive tumor microenvironment in children, adolescents, and young adults with Hodgkin's lymphoma may improve early response rates and eliminate toxic chemotherapy and radiation, thus minimizing toxicity. We conducted a phase II study to evaluate the safety and overall response rate of brentuximab vedotin and rituximab in combination with risk-adapted chemotherapy in children, adolescents, and young adults with newly diagnosed classic Hodgkin's lymphoma (cHL).
This is a prospective, phase II, non-randomized, risk-assigned study. Patients were treated and evaluated between 2012 and 2020. Eligible patients were aged ≥1 and ≤30 years old with advanced stage, intermediate-risk, and high-risk newly diagnosed cHL. Patients received four or six cycles of brentuximab vedotin (1.2 mg/kg), doxorubicin (25 mg/m), vinblastine (6 mg/m), dacarbazine (375 mg/m), and rituximab (375 mg/m). Early response was evaluated following two cycles of therapy. Involved field radiotherapy (IFRT) was restricted to high-risk patients with both bulky disease and slow response or those not in complete response at the end of chemoimmunotherapy.
Thirty patients were enrolled, with a median age of 15 years (4-23). There were 18 intermediate-risk and 12 high-risk patients. Toxicities included grade III mucositis (3%), infusion reaction (3%), and peripheral neuropathy (6%). There was a 100% complete response rate on completion of chemoimmunotherapy. Eighteen patients (60%) achieved a rapid early response. Four patients (13%) required IFRT. The 5-year event-free and overall survival rates were 100%, with a median follow-up of 62 months (18-105).
Immunotherapy with brentuximab vedotin, rituximab, and risk-adapted chemotherapy is safe in children, adolescents, and young adults with newly diagnosed cHL. We have demonstrated 100% complete response and 100% event-free and overall survival rates at a median 5-year follow-up, with a significant reduction in use of more toxic chemotherapy and IFRT. A larger cohort is required to confirm these preliminary findings.
NCT02398240.
霍奇金淋巴瘤的治愈率很高，但治疗引起的短期和长期并发症仍然令人担忧。针对儿童、青少年和年轻成人霍奇金淋巴瘤的肿瘤抗原和免疫抑制性肿瘤微环境的免疫疗法，可能会提高早期反应率，并消除有毒的化疗和放疗，从而将毒性降至最低。我们进行了一项 II 期研究，以评估在新诊断的经典霍奇金淋巴瘤（cHL）患儿、青少年和年轻成人中，博纳吐单抗维布妥昔单抗联合利妥昔单抗与风险适应性化疗联合的安全性和总体反应率。
这是一项前瞻性、II 期、非随机、风险分配的研究。患者于 2012 年至 2020 年期间接受治疗和评估。符合条件的患者年龄≥1 岁且≤30 岁，患有晚期、中危和高危新发 cHL。患者接受博纳吐单抗维布妥昔单抗（1.2mg/kg）、多柔比星（25mg/m）、长春碱（6mg/m）、达卡巴嗪（375mg/m）和利妥昔单抗（375mg/m）的四或六周期治疗。在两个周期的治疗后评估早期反应。受累野放疗（IFRT）仅限于疾病体积大且反应缓慢或在化疗免疫治疗结束时未完全缓解的高危患者。
共纳入 30 例患者，中位年龄为 15 岁（4-23 岁）。其中 18 例为中危患者，12 例为高危患者。毒性包括 3%的 3 级粘膜炎、3%的输液反应和 6%的周围神经病变。完成化疗免疫治疗后，完全缓解率为 100%。18 例（60%）患者快速早期反应。4 例（13%）患者需要 IFRT。5 年无事件生存率和总生存率均为 100%，中位随访时间为 62 个月（18-105 个月）。
博纳吐单抗维布妥昔单抗、利妥昔单抗联合风险适应性化疗在新诊断的 cHL 儿童、青少年和年轻成人中是安全的。我们在中位 5 年随访时，显示了 100%的完全缓解率、100%的无事件生存率和总生存率，并且显著减少了更有毒性的化疗和 IFRT 的使用。需要更大的队列来证实这些初步发现。
NCT02398240。
