A Study of Inotuzumab Ozogamicin in Chinese Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia

CR: disappearance of leukemia as indicated by <5% marrow blasts and the absence of peripheral blood leukemic blasts, with recovery of hematopoiesis defined by absolute neutrophil count (ANC) >=1000 per microliter (/mcL) and platelets >=100,000/mcL. C1 extramedullary disease (EMD) status was required (disappearance of all measurable and non-measurable EMD with the exception of lesions for which following must be true: participants with at least 1 measurable lesion, all nodal masses >1.5 centimeter (cm) in greatest transverse diameter (GTD) at baseline regressed to <=1.5 cm in GTD and nodal masses >=1 cm and <=1.5 cm in GTD at baseline must have regressed to <1 cm GTD or reduced by 75% in sum of products of greatest diameters (SPD). No new lesions. Spleen and other previously enlarged organs must have regressed in size and must not be palpable. All diseases were assessed using the same technique as at baseline. CRi: CR except with ANC <1000/mcL and/or platelets <100,000/mcL.

DoR: from date of first CR/CRi to date of disease progression (objective progression, relapse from CR/CRi), death due to any cause, whichever occurred first. CR: disappearance of leukemia as indicated by <5% marrow blasts and absence of peripheral blood leukemic blasts, with recovery of hematopoiesis defined by ANC >=1000 per microliter (/mcL) and platelets >=10^5/mcL. C1 EMD status was required (disappearance of all measurable and non-measurable EMD with the exception of lesions for which following must be true: participants with at least 1 measurable lesion, all nodal masses >1.5 cm in GTD at baseline regressed to <=1.5 cm in GTD and nodal masses >=1 cm and <=1.5 cm in GTD at baseline must have regressed to <1 cm GTD or reduced by 75% in SPD. No new lesions. Spleen and other previously enlarged organs must have regressed in size and must not be palpable. All diseases must be assessed using same technique as at baseline. CRi: CR except with ANC <1000/mcL and/or platelets <10^5/mcL.

MRD negativity was defined as malignant B lymphocytes occurring at frequency <10^4. CR: disappearance of leukemia as indicated by <5% marrow blasts and absence of peripheral blood leukemic blasts, with recovery of hematopoiesis defined by ANC >=1000 per microliter (/mcL) and platelets >=10^5/mcL. C1 EMD status was required (disappearance of all measurable and non-measurable EMD with the exception of lesions for which following must be true: participants with at least 1 measurable lesion, all nodal masses >1.5 cm in GTD at baseline regressed to <=1.5 cm in GTD and nodal masses >=1 cm and <=1.5 cm in GTD at baseline must have regressed to <1 cm GTD or reduced by 75% in SPD. No new lesions. Spleen and other previously enlarged organs must have regressed in size and must not be palpable. All diseases must be assessed using same technique as at baseline. CRi: CR except with ANC <1000/mcL and/or platelets <10^5/mcL.

PFS: from date of first dose to date of disease progression (objective progression, relapse from CR/CRi), or death due to any cause, whichever occurred first. CR: disappearance of leukemia as indicated by <5% marrow blasts and absence of peripheral blood leukemic blasts, with recovery of hematopoiesis defined by ANC >=1000 per microliter (/mcL) and platelets >=10^5/mcL. C1 EMD status was required (disappearance of all measurable and non-measurable EMD with the exception of lesions for which following must be true: participants with at least 1 measurable lesion, all nodal masses >1.5 cm in GTD at baseline regressed to <=1.5 cm in GTD and nodal masses >=1 cm and <=1.5 cm in GTD at baseline must have regressed to <1 cm GTD or reduced by 75% in SPD. No new lesions. Spleen and other previously enlarged organs must have regressed in size and must not be palpable. All diseases must be assessed using same technique as at baseline. CRi: CR except with ANC <1000/mcL and/or platelets <10^5/mcL.

OS was defined as the time from date of first dose to the date of death due to any cause. Participants without confirmation of death were to be censored on date of last contact.

Participants who proceeded to HSCT was reported. HSCT is a procedure where multipotent hematopoietic stem cells are transplanted from sources such as bone marrow, peripheral blood, or umbilical cord blood. These stem cells can replicate inside a participant and produce additional normal blood cells.

An AE was defined as any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. AEs included both serious and all non-serious adverse events. SAE was defined as any untoward medical occurrence that, at any dose resulted in any of the following outcomes: death; life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; or that was considered as an important medical event. According to NCI CTCAE version 5: Grade 1= mild AE; Grade 2= moderate AE; Grade 3=severe AE; Grade 4= life-threatening consequences and urgent intervention indicated; Grade 5= death related to AE. An AE was considered treatment-emergent relative to a given treatment if the event start date is during the on-treatment period (including on the date of first dose).

An AE was defined as any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. An SAE was defined as any untoward medical occurrence that, at any dose resulted in any of the following outcomes: death; life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; or that was considered as an important medical event. According to NCI CTCAE version 5: Grade 1= mild AE; Grade 2= moderate AE; Grade 3=severe AE; Grade 4= life-threatening consequences and urgent intervention indicated, Grade 5= death related to AE. An AE was considered treatment-emergent relative to a given treatment if the event start date is during the on-treatment period (including on the date of first dose).

An AE was defined as any untoward medical occurrence in a participant temporally associated with use of study intervention, whether or not considered related to study intervention. AEs included both serious and all non-serious adverse events. SAE was defined as any untoward medical occurrence that, at any dose resulted in any of following outcomes: death; life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; or that was considered as an important medical event. According to NCI CTCAE version 5: Grade 1= mild AE; Grade 2= moderate AE; Grade 3=severe AE; Grade 4= life-threatening consequences and urgent intervention indicated, Grade 5= death related to AE. An AE was considered treatment-emergent relative to a given treatment if event start date is during on-treatment period (including on date of first dose). Relatedness to study drug was assessed by investigator.

An AE was defined as any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. According to NCI CTCAE version 5: Grade 1= mild AE; Grade 2= moderate AE; Grade 3=severe AE; Grade 4= life-threatening consequences and urgent intervention indicated, Grade 5= death related to AE.

Hematology parameters included white blood cell count (with differential including blast count1), hemoglobin and platelet count. Grade 2: moderate; minimal, local or noninvasive intervention indicated; Grade 3: severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care; Grade 4: life-threatening consequences.

Chemistry parameters included sodium, potassium, magnesium, calcium, creatinine, albumin, alanine aminotransferase, aspartate aminotransferase, glucose, phosphorus, total bilirubin, direct bilirubin only if total is elevated, blood urea nitrogen or urea, uric acid or urate, alkaline phosphatase, lactate dehydrogenase, gamma glutamyl transpeptidase, total protein, amylase and/or lipase. Grade 2: moderate; minimal, local or noninvasive intervention indicated; Grade 3: severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care; Grade 4: life-threatening consequences.

Criteria for VOD were defined as (i) classical VOD (first 21 days after HSCT): bilirubin greater than or equal to 2 mg/dL and two (or more) of the following criteria must also be present; painful hepatomegaly, weight gain >5%, ascites. (ii) late onset VOD (>21 days after HSCT): classical VOD beyond day 21 or histologically proven VOD; or two or more of the following criteria must be present: bilirubin >2 mg/dL; painful hepatomegaly; weight gain >5%; ascites.

Cmax was defined as maximum observed plasma concentration. Cmax was observed directly from data.

Ctrough was observed directly from data.

A participant was ADA or NAb positive if (i) baseline titer was missing or negative and participant had >=1 post treatment positive titer (treatment-induced), or (ii) positive titer at baseline and had a >=0.602 unit increase in titer (log10) from baseline in >=1 post-treatment sample (treatment-boosted).