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Rituximab in B-Lineage Adult Acute Lymphoblastic Leukemia

Sébastien Maury ... 肿瘤 • 2016.09.15
• CD19 CAR治疗急性淋巴细胞白血病的长期随访研究 • tisagenlecleucel治疗儿童和年轻成人B细胞淋巴细胞白血病



利妥昔单抗治疗已经改善了非霍奇金淋巴瘤患者的结局。B系急性淋巴细胞白血病(acute lymphoblastic leukemia,ALL)患者也可能表达利妥昔单抗的靶点——CD20抗原。尽管单组研究提示利妥昔单抗治疗联合化疗可以改善该类患者的结局,但是这一假设尚未在随机试验中得到验证。



我们将CD20抗原阳性、费城染色体(Philadelphia chromosome,Ph)阴性的成年ALL患者(18~59岁)随机分配为只接受化疗组或者接受利妥昔单抗治疗联合化疗组,并以无事件生存作为主要终点。在所有治疗阶段均进行了利妥昔单抗输注,共计16~18次。



从2006年5月至2014年4月,共计入组了209名患者:105名归于利妥昔单抗组,104名归于对照组。在30个月的中位随访时间之后,利妥昔单抗组的无事件生存期比对照组长(风险比为0.66;95%置信区间[CI]为0.45~0.98;P=0.04);估计的2年无事件生存率分别为65%(95% CI为56%~75%)和52%(95% CI为43%~63%)。在多变量分析中利妥昔单抗治疗仍与更长的无事件生存期相关。两组患者间严重不良事件的总体发生率无显著性差异,但是在利妥昔单抗组中观察到对天冬酰胺酶的过敏反应更少。



在针对ALL的化疗方案中增加使用利妥昔单抗改善了CD20抗原阳性、费城染色体阴性的ALL年轻成年患者的结局(该研究由巴黎区域临床研究办公室[Regional Clini­cal Research Office, Paris]等资助;ClinicalTrials.gov注册号为NCT00327678)。


Sébastien Maury, M.D., Ph.D., Sylvie Chevret, M.D., Ph.D., Xavier Thomas, M.D., Ph.D., Dominik Heim, M.D., Thibaut Leguay, M.D., Françoise Huguet, M.D., Patrice Chevallier, M.D., Ph.D., Mathilde Hunault, M.D., Ph.D., Nicolas Boissel, M.D., Ph.D., Martine Escoffre‑Barbe, M.D., Urs Hess, M.D., Norbert Vey, M.D., Jean‑Michel Pignon, M.D., Thorsten Braun, M.D., Ph.D., Jean‑Pierre Marolleau, M.D., Ph.D., Jean‑Yves Cahn, M.D., Yves Chalandon, M.D., Véronique Lhéritier, R.N., M.P.H., Kheira Beldjord, Pharm.D., Ph.D., Marie C. Béné, Pharm.D., Ph.D., Norbert Ifrah, M.D., and Hervé Dombret, M.D., for GRAALL*
The authors’ affiliations are listed in the Appendix. Address reprint requests to Dr. Dombret at Institut Universitaire d’Hématologie, EA-3518, Hôpital Saint-Louis, Université Paris Diderot, 1 ave. Claude Vellefaux, 75475 Paris CEDEX 10, France, or at herve.dombret@sls.aphp.fr. * A complete list of the Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL) centers and investigators is provided in the Supplementary Appendix, available at NEJM.org.



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