Inotuzumab ozogamicin with bosutinib for relapsed or refractory Philadelphia chromosome positive acute lymphoblastic leukemia or lymphoid blast phase of chronic myeloid leukemia

被引:33
|
作者
Jain, Nitin [1 ]
Maiti, Abhishek [1 ]
Ravandi, Farhad [1 ]
Konopleva, Marina [1 ]
Daver, Naval [1 ]
Kadia, Tapan [1 ]
Pemmaraju, Naveen [1 ]
Short, Nicholas [1 ]
Kebriaei, Partow [2 ]
Ning, Jing [3 ]
Cortes, Jorge [4 ]
Jabbour, Elias [1 ]
Kantarjian, Hagop [1 ]
机构
[1] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, 1515 Holcombe Blvd,Unit 428, Houston, TX 77030 USA
[2] Univ Texas MD Anderson Canc Ctr, Dept Stem Cell Transplantat & Cellular Therapy, Houston, TX 77030 USA
[3] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA
[4] Augusta Univ, Georgia Canc Ctr, Augusta, Georgia
关键词
TYROSINE KINASE INHIBITOR; BLINATUMOMAB; IMATINIB; CHEMOTHERAPY; DASATINIB; EFFICACY; SAFETY; ADULTS;
D O I
10.1002/ajh.26238
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Relapsed/refractory (R/R) Philadelphia chromosome positive acute lymphoblastic leukemia (Ph + ALL) and lymphoid blast phase of chronic myeloid leukemia (LBP-CML) have poor outcomes. We designed a phase 1/2 study combining inotuzumab ozogamicin with bosutinib for this patient population. Patients with T315I mutation were excluded. Bosutinib was administered daily at three dose levels (300 mg/d, 400 mg/d, 500 mg/d) in a 3 + 3 design. Inotuzumab ozogamicin was dosed weekly during cycle one, and once every 4 weeks subsequently for a total of six cycles. The primary objective was to determine the safety and the maximum tolerated dose (MTD) of bosutinib in combination with inotuzumab ozogamicin. Eighteen patients were enrolled (Ph-positive ALL, n = 16; LBP-CML, n = 2). The median age was 62 years (range, 19-74) and the median number of prior therapies was one (range, 1-5). Dose limiting toxicities included grade 3 skin rash and bosutinib 400 mg daily was determined as the MTD. The most frequent grade 3/4 treatment-emergent adverse events were thrombocytopenia (60%) and neutropenia (38%). A complete response (CR) / CR with incomplete count recovery (CRi) was achieved in 15/18 (83%) patients; 11/18 (61%) patients achieved negative measurable residual disease by flow cytometry. Complete molecular response was noted in 10/18 (56%) patients. The 30-day mortality was 0%. After a median follow-up of 44 months, the median duration of response and overall survival were 7.7 months and 13.5 months, respectively. Six patients had a subsequent allogeneic stem cell transplant. No patient developed veno-occlusive disease. Inotuzumab ozogamicin with bosutinib was well tolerated in R/R Ph-positive ALL and LBP-CML.
引用
收藏
页码:1000 / 1007
页数:8
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