Inotuzumab ozogamicin as single agent in pediatric patients with relapsed and refractory acute lymphoblastic leukemia: results from a phase II trial

被引:45
作者
Pennesi, Edoardo [1 ,2 ]
Michels, Naomi [1 ,2 ,3 ]
Brivio, Erica [1 ,2 ]
van der Velden, Vincent H. J. [4 ]
Jiang, Yilin [1 ]
Thano, Adriana [1 ]
Ammerlaan, Anneke J. C. [1 ,2 ]
Boer, Judith M. [1 ,3 ]
Beverloo, H. Berna [5 ]
Sleight, Barbara [6 ]
Chen, Ying [6 ]
Vormoor-Buerger, Britta [1 ]
Rives, Susana [7 ,8 ]
Bielorai, Bella [9 ]
Roessig, Claudia [10 ]
Petit, Arnaud [11 ]
Rizzari, Carmelo [12 ]
Engstler, Gernot [13 ]
Stary, Jan [14 ]
Bautista Sirvent, Francisco J. [1 ,15 ]
Chen-Santel, Christiane [16 ,17 ]
Bruno, Benedicte [18 ]
Bertrand, Yves [19 ]
Rialland, Fanny [20 ]
Plat, Genevieve [21 ]
Reinhardt, Dirk [22 ]
Vinti, Luciana [23 ]
Von Stackelberg, Arend [16 ,24 ]
Locatelli, Franco [23 ]
Zwaan, Christian M. [1 ,2 ]
机构
[1] Princess Maxima Ctr Pediat Oncol, Utrecht, Netherlands
[2] Erasmus MC Sophia Childrens Hosp, Dept Pediat Oncol, Rotterdam, Netherlands
[3] Oncode Inst, Utrecht, Netherlands
[4] Univ Med Ctr Rotterdam, Dept Immunol, Erasmus MC, Rotterdam, Netherlands
[5] Univ Med Ctr Rotterdam, Dept Clin Genet, Erasmus MC, Rotterdam, Netherlands
[6] Pfizer Inc, Groton, CT 06340 USA
[7] Hosp St Joan de Deu Barcelona, Pediat Oncol & Hematol Dept, Barcelona, Spain
[8] Inst Recerca St Joan de Deu, Barcelona, Spain
[9] Sheba Med Ctr, Div Pediat Hematol & Oncol, Ramat Gan, Israel
[10] Univ Childrens Hosp Muenster, Pediat Hematol & Oncol, Munster, Germany
[11] Sorbonne Univ, Dept Pediat Hematol & Oncol, Hop Armand Trousseau, AP HP, Paris, France
[12] Univ Milano Bicocca, MBBM Fdn, Dept Pediat, Pediat Hematol Oncol Unit,ASST Monza, Monza, Italy
[13] Med Univ Vienna, St Anna Childrens Hosp, Vienna, Austria
[14] Univ Hosp Motol, Dept Pediat Hematol & Oncol, Prague, Czech Republic
[15] Hosp Nino Jesus, Dept Pediat Oncol & Hematol, Madrid, Spain
[16] Charite Univ Med Berlin, Div Oncol & Hematol, Dept Pediat, Berlin, Germany
[17] Rostock Univ, Dept Pediat, Med Ctr, Rostock, Germany
[18] CHRU Lille, Hop Jeanne de Flandre, Pediat Hematol, Lille, France
[19] Claude Bernard Univ, Civil Hosp Lyon, Inst Pediat Hematol & Oncol, Lyon, France
[20] Nantes Univ Hosp, Serv Oncohematol Pediat, Hop Mere Enfant, Nantes, France
[21] CHU Toulouse, Serv Hematol Immunol Oncol, Hop Enfants, Toulouse, France
[22] Essen Univ Hosp, Dept Pediat Oncol, Essen, Germany
[23] Univ Rome, Dept Hematol Oncol & Cell & Gene Therapy, IRCCS Osped Pediat Bambino Gesu, Rome, Italy
[24] IntReALL Study Grp, Berlin, Germany
关键词
ACUTE MYELOID-LEUKEMIA; GEMTUZUMAB OZOGAMICIN; CONSECUTIVE TRIALS; CALICHEAMICIN; CHILDREN; EXPRESSION; DISEASE; CMC-544; BFM;
D O I
10.1038/s41375-022-01576-3
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Inotuzumab Ozogamicin is a CD22-directed antibody conjugated to calicheamicin, approved in adults with relapsed or refractory (R/R) B cell acute lymphoblastic leukemia (BCP-ALL). Patients aged 1-18 years, with R/R CD22 + BCP-ALL were treated at the RP2D of 1.8 mg/m(2). Using a single-stage design, with an overall response rate (ORR) <= 30% defined as not promissing and ORR > 55% as expected, 25 patients needed to be recruited to achieve 80% power at 0.05 significance level. Thirty-two patients were enrolled, 28 were treated, 27 were evaluable for response. The estimated ORR was 81.5% (95%CI: 61.9-93.7%), and 81.8% (18/22) of the responding subjects were minimal residual disease (MRD) negative. The study met its primary endpoint. Median follow up of survivors was 16 months (IQR: 14.49-20.07). One year Event Free Survival was 36.7% (95% CI: 22.2-60.4%), and Overall Survival was 55.1% (95% CI: 39.1-77.7%). Eighteen patients received consolidation (with HSCT and/or CAR T-cells therapy). Sinusoidal obstructive syndrome (SOS) occurred in seven patients. MRD negativity seemed correlated to calicheamicin sensitivity in vitro, but not to CD22 surface expression, saturation, or internalization. InO was effective in this population. The most relevant risk was the occurrence of SOS, particularly when InO treatment was followed by HSCT.
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收藏
页码:1516 / 1524
页数:9
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