硫酸长春新碱脂质体注射液联合化疗用于复发急性淋巴细胞白血病儿童、青少年和青年成人：儿童白血病和淋巴瘤治疗进展协作组试验

Vincristine Sulfate Liposome Injection With Combination Chemotherapy for Children, Adolescents, and Young Adults With Relapsed Acute Lymphoblastic Leukemia: A Therapeutic Advances in Childhood Leukemia and Lymphoma Consortium Trial.

作者信息

Shah Nirali N, Schafer Eric S, Chi Yueh-Yun, Malvar Jemily, Heym Kenneth M, Place Andrew E, Burns Melissa, Chang Bill H, Slone Tamra, Verma Anupam, Gossai Nathan, Shaw Peter H, Burke Michael J, Hermiston Michelle, Schore Reuven J, Cooper Todd, Pauly Melinda, Rushing Teresa, Jarosinski Paul, Florendo Ellynore, Yates Bonnie, Widemann Brigitte C, Peer Cody J, Figg William D, Silverman Lewis B, Bhojwani Deepa, Wayne Alan S

机构信息

Pediatric Oncology Branch, National Cancer Institute/Center for Cancer Research, National Institutes of Health, Bethesda, Maryland, USA.

Division of Hematology/Oncology, Department of Pediatrics, Baylor College of Medicine and Texas Children's Cancer and Hematology Center, Houston, Texas, USA.

出版信息

Pediatr Blood Cancer. 2025 May;72(5):e31584. doi: 10.1002/pbc.31584. Epub 2025 Feb 12.

DOI:10.1002/pbc.31584

PMID:39937083

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12278299/

Abstract

INTRODUCTION

Vincristine sulfate liposome injection (VSLI), a liposomal formulation of vincristine, may be better tolerated than standard aqueous vincristine and enable dose intensification.

PROCEDURES

Based on single-agent tolerability, activity, and FDA approval in adults with acute lymphoblastic leukemia (ALL), we tested the safety and feasibility of VSLI as replacement for standard vincristine in the UK ALL R3 mitoxantrone-based four-drug induction (Cohort A), a three-drug anthracycline-free induction (Cohort B), and maintenance chemotherapy (Cohort C) in children and young adults with relapsed/refractory B-cell ALL.

RESULTS

Among 29 participants with a median age of 12.4 years (range: 1.8-19.6 years), 16 received Cohort A, eight received Cohort B, and five received Cohort C therapy. Dose level 1 (DL1): 1.5 mg/m and dose level 2 (DL2): 2 mg/m of VSLI, each without a dose cap, were tested. Collectively, the median VSLI dose administered was 1.9 mg (range: 0.71-4.06 mg), and 13 (44.8%) received a dose above the standard 2 mg vincristine dose cap. Dose-limiting toxicities (DLTs) at DL2 were seen in three patients, two in Cohort A and one in Cohort B, prompting further evaluation at DL1 for both cohorts. No DLTs were experienced at DL1. Only DL2 was tested in Cohort C-without DLT. Complete remissions were seen in 14 of 16 (87.5%) participants in Cohort A; three of eight (37.5%) in Cohort B; and one (20%) in Cohort C. VSLI with combination chemotherapy at DL1 was generally well tolerated.

CONCLUSION

Based on the promising response signal in this heavily pretreated population, further study of VSLI is warranted. (ClinicalTrials.gov NCT02879643).

摘要

引言

硫酸长春新碱脂质体注射液（VSLI）是长春新碱的脂质体制剂，其耐受性可能优于标准的长春新碱水溶液，并且能够增加剂量强度。

方法

基于单药耐受性、活性以及美国食品药品监督管理局（FDA）对成人急性淋巴细胞白血病（ALL）的批准，我们在英国ALL R3以米托蒽醌为基础的四药诱导方案（队列A）、无蒽环类药物的三药诱导方案（队列B）以及复发/难治性B细胞ALL儿童和青年的维持化疗（队列C）中，测试了VSLI替代标准长春新碱的安全性和可行性。

结果

29名参与者的中位年龄为12.4岁（范围：1.8 - 19.6岁），其中16人接受队列A治疗，8人接受队列B治疗，5人接受队列C治疗。测试了VSLI的剂量水平1（DL1）：1.5mg/m²和剂量水平2（DL2）：2mg/m²，均无剂量上限。总体而言，给予的VSLI中位剂量为1.9mg（范围：0.71 - 4.06mg），13人（44.8%）接受的剂量高于标准长春新碱2mg的剂量上限。在DL2观察到3例剂量限制性毒性（DLT），队列A中有2例，队列B中有1例，促使对两个队列在DL1进行进一步评估。在DL1未观察到DLT。队列C仅测试了DL2，未出现DLT。队列A的16名参与者中有14人（87.5%）达到完全缓解；队列B的8人中有3人（37.5%）；队列C的1人（20%）。DL1的VSLI联合化疗总体耐受性良好。