From the Département d'Hématologie, Hôpital Henri Mondor, Assistance Publique-Hôpitaux de Paris (AP-HP), Institut Mondor de Recherche Biomédicale (équipe 21), Université Paris Est, Creteil (S.M.), Service de Biostatistique (S.C.) and Département d'Hématologie (N.B., K.B., H.D.), Hôpital Saint-Louis, AP-HP, Institut Universitaire d'Hématologie, Université Paris Diderot, Paris, Département d'Hématologie (X.T.) and Group for Research on Adult Acute Lymphoblastic Leukemia Coordination Office (V.L.), Hospices Civils de Lyon, Hôpital Lyon Sud, Pierre-Bénite, Département d'Hématologie, Centre Hospitalier Universitaire (CHU) Haut-Lévêque, Pessac (T.L.), Département d'Hématologie, Institut Universitaire du Cancer, Toulouse (F.H.), Département d'Hématologie Clinique, CHU Hôtel Dieu (P.C.), and Service d'Hématologie Biologique, CHU (M.C.B.), Nantes, Département d'Hématologie, CHU, Angers (M.H., N.I.), Département d'Hématologie, CHU, Rennes (M.E.-B.), Département d'Hématologie, Institut Paoli-Calmettes, Marseille (N.V.), Département d'Hématologie, Centre Hospitalier de Dunkerque, Dunkirk (J.-M.P.), Département d'Hématologie, Hôpital Avicenne, AP-HP, Université Paris Nord, Bobigny (T.B.), Département d'Hématologie, CHU, Université Picardie Jules Verne, Amiens ( J.-P.M.), and Département d'Hématologie, CHU, Grenoble ( J.-Y.C.) - all in France; and the Klinik für Hämatologie, Universitätsspital, Basel (D.H.), Swiss Group for Clinical Cancer Research, Bern (D.H., U.H., Y.C.), Klinik für Onkologie-Hämatologie, Kantonsspital St. Gallen, St. Gallen (U.H.), and Division of Hematology, Department of Medical Specialties, University Hospital and University of Geneva, Geneva (Y.C.) - all in Switzerland.
N Engl J Med. 2016 Sep 15;375(11):1044-53. doi: 10.1056/NEJMoa1605085.
Treatment with rituximab has improved the outcome for patients with non-Hodgkin's lymphoma. Patients with B-lineage acute lymphoblastic leukemia (ALL) may also have the CD20 antigen, which is targeted by rituximab. Although single-group studies suggest that adding rituximab to chemotherapy could improve the outcome in such patients, this hypothesis has not been tested in a randomized trial.
We randomly assigned adults (18 to 59 years of age) with CD20-positive, Philadelphia chromosome (Ph)-negative ALL to receive chemotherapy with or without rituximab, with event-free survival as the primary end point. Rituximab was given during all treatment phases, for a total of 16 to 18 infusions.
From May 2006 through April 2014, a total of 209 patients were enrolled: 105 in the rituximab group and 104 in the control group. After a median follow-up of 30 months, event-free survival was longer in the rituximab group than in the control group (hazard ratio, 0.66; 95% confidence interval [CI], 0.45 to 0.98; P=0.04); the estimated 2-year event-free survival rates were 65% (95% CI, 56 to 75) and 52% (95% CI, 43 to 63), respectively. Treatment with rituximab remained associated with longer event-free survival in a multivariate analysis. The overall incidence rate of severe adverse events did not differ significantly between the two groups, but fewer allergic reactions to asparaginase were observed in the rituximab group.
Adding rituximab to the ALL chemotherapy protocol improved the outcome for younger adults with CD20-positive, Ph-negative ALL. (Funded by the Regional Clinical Research Office, Paris, and others; ClinicalTrials.gov number, NCT00327678 .).
利妥昔单抗治疗改善了非霍奇金淋巴瘤患者的预后。B 细胞急性淋巴细胞白血病（ALL）患者也可能具有 CD20 抗原，利妥昔单抗可靶向该抗原。虽然单组研究表明，在这类患者的化疗中添加利妥昔单抗可改善预后，但这一假设尚未在随机试验中得到检验。
我们将 CD20 阳性、费城染色体（Ph）阴性 ALL 成人（年龄 18 至 59 岁）随机分为接受利妥昔单抗联合化疗或单纯化疗组，以无事件生存为主要终点。利妥昔单抗在所有治疗阶段使用，总共输注 16 至 18 次。
2006 年 5 月至 2014 年 4 月，共纳入 209 例患者：利妥昔单抗组 105 例，对照组 104 例。中位随访 30 个月后，利妥昔单抗组无事件生存时间长于对照组（风险比，0.66；95%置信区间 [CI]，0.45 至 0.98；P=0.04）；估计 2 年无事件生存率分别为 65%（95% CI，56 至 75）和 52%（95% CI，43 至 63）。多变量分析显示，利妥昔单抗治疗与无事件生存时间延长相关。两组严重不良事件的总发生率无显著差异，但利妥昔单抗组的门冬酰胺酶过敏反应较少。
在 ALL 化疗方案中添加利妥昔单抗可改善 CD20 阳性、Ph 阴性 ALL 年轻成人的预后。（由巴黎地区临床研究办公室及其他机构资助；ClinicalTrials.gov 注册号，NCT00327678）。
