Children's Hospital of Philadelphia, Division of Oncology and Center for Childhood Cancer Research, Philadelphia, Pennsylvania.
San Francisco Benioff Children's Hospital and School of Medicine, Pediatrics, Division of Pediatric Bone Marrow Transplantation, University of California, San Francisco, California.
Pediatr Blood Cancer. 2021 Jan;68(1):e28718. doi: 10.1002/pbc.28718. Epub 2020 Oct 24.
The treatment paradigm for patients with relapsed/refractory B-cell acute lymphoblastic leukemia (rrALL) has been revolutionized given recent clinical trials demonstrating remarkable success of immunotherapies and leading to drug approvals by United States and European agencies. We report experience with commercial blinatumomab and inotuzumab use at two North American pediatric oncology centers in children and adolescents/young adults with B-ALL.
Patients 0-25 years old treated with the CD19 × CD3 bispecific T cell-engaging antibody blinatumomab and/or the CD22 antibody-drug conjugate inotuzumab from January 1, 2010, to June 1, 2018, were eligible. Disease status included relapsed B-ALL in second or greater relapse, primary chemotherapy-refractory B-ALL, or B-ALL complicated by severe infection precluding delivery of conventional chemotherapy.
We identified 27 patients who received blinatumomab and/or inotuzumab outside of clinical trials during the study period. Four of the 13 patients (31%) with relapsed disease achieved minimal residual disease (MRD)-negative remission, and five patients (39%) underwent hematopoietic stem cell transplant (HSCT). In the 12 patients with primary chemorefractory B-ALL treated with immunotherapy, 11 (92%) achieved MRD-negative remission as assessed by flow cytometry; 10 patients (83%) underwent subsequent HSCT. Two patients with B-ALL in MRD-negative remission received blinatumomab due to severe infection and remained in remission after chemotherapy continuation.
Blinatumomab and inotuzumab can induce deep remissions in patients with rrALL and facilitate subsequent HSCT or other cellular therapies. Blinatumomab can also serve as an effective bridging therapy during severe infection. The optimal timing, choice of immunotherapeutic agent(s), and duration of responses require further investigation via larger-scale clinical trials.
鉴于最近的临床试验证明免疫疗法取得了显著成功，并促使美国和欧洲机构批准了药物，复发/难治性 B 细胞急性淋巴细胞白血病（rrALL）患者的治疗模式发生了革命性变化。我们报告了在北美两家儿科肿瘤中心，在儿童和青少年/年轻成人 B-ALL 患者中使用商业性blinatumomab 和 inotuzumab 的经验。
符合条件的患者为 2010 年 1 月 1 日至 2018 年 6 月 1 日期间接受 CD19×CD3 双特异性 T 细胞结合抗体blinatumomab 和/或 CD22 抗体药物偶联物 inotuzumab 治疗的 0-25 岁患者。疾病状态包括第二次或更多次复发的 B-ALL、原发性化疗耐药性 B-ALL 或因严重感染而无法接受常规化疗的 B-ALL。
在研究期间，我们在临床试验之外确定了 27 名接受blinatumomab 和/或 inotuzumab 治疗的患者。在 13 名复发疾病患者中，有 4 名（31%）达到微小残留病（MRD）阴性缓解，5 名患者（39%）接受了造血干细胞移植（HSCT）。在接受免疫治疗的 12 名原发性化疗耐药性 B-ALL 患者中，11 名（92%）通过流式细胞术评估达到 MRD 阴性缓解；10 名患者（83%）接受了后续 HSCT。2 名 MRD 阴性缓解的 B-ALL 患者因严重感染接受了blinatumomab 治疗，并在继续化疗后仍处于缓解状态。
blinatumomab 和 inotuzumab 可诱导 rrALL 患者深度缓解，并促进随后的 HSCT 或其他细胞治疗。blinatumomab 也可作为严重感染期间的有效桥接治疗。通过更大规模的临床试验，需要进一步研究免疫治疗剂的最佳时机、选择和反应持续时间。
