Nilotinib in Newly Diagnosed Adult Philadelphia Chromosome & /or BCR-ABL Positive Chronic Myeloid Leukaemia in Chronic Phase

MR4\^0 was defined as either (i) detectable disease ≤ 0.01% BCR-ABL ratio (international scale (IS)) with mean ABL transcripts ≥ 10 000 or (ii) undetectable disease in complementary deoxyribonucleic acid (cDNA) with ≥ 10 000 ABL transcripts.

Time frame: at 18 months

Population: Intent-to-treat\_Molecular (ITT\_MR) analysis set was a subset of the ITT population including the patients with typical BCR-ABL transcript at screening.

The following events were considered disease progression to AP/BC: Death due to disease under study; AP, as defined by any of the following: ≥ 15% blasts in the peripheral blood or bone marrow, but \< 30% blasts in both the peripheral blood and bone marrow, ≥ 30% blasts plus promyelocytes in peripheral blood or bone marrow, ≥ 20% basophils in the peripheral blood, Thrombocytopenia (\< 100 × 109/L) that was unrelated to therapy, Evidence of clonal evolution, as determined by medical review with consensus of the SSMC/DMC. BC was defined as: ≥ 30% blasts in peripheral blood or bone marrow, Appearance of extramedullary involvement other than hepatosplenomegaly proven by biopsy.

Time frame: at 12 and 24 months

Population: The intent-to-treat (ITT) population consisted of all patients who received at least one dose of study drug.

The following events were considered disease progression to AP/BC: Death due to disease under study; AP, as defined by any of the following: ≥ 15% blasts in the peripheral blood or bone marrow, but \< 30% blasts in both the peripheral blood and bone marrow, ≥ 30% blasts plus promyelocytes in peripheral blood or bone marrow, ≥ 20% basophils in the peripheral blood, Thrombocytopenia (\< 100 × 109/L) that was unrelated to therapy, Evidence of clonal evolution, as determined by medical review with consensus of the SSMC/DMC. BC was defined as: ≥ 30% blasts in peripheral blood or bone marrow, Appearance of extramedullary involvement other than hepatosplenomegaly proven by biopsy.

Time frame: at 12 months

Population: The intent-to-treat (ITT) population consisted of all patients who received at least one dose of study drug.

CCyR parameters were defined as 0% Philadelphia positive (Ph+) metaphases. Loss of CCyR was defined as a patient exceeding the CCyR criteria (ie, \> 0% Ph+ metaphases) at a subsequent visit after the patient had achieved CCyR.

Time frame: 12 and 24 months

Population: The ITT\_CyR population was a subset of the ITT population including the Ph+ patients at screening was considered. Patients who had either no metaphases recorded at screening bone marrow or only negative metaphases recorded at screening bone marrow but had Ph+ metaphases at any visits after screening were also part of this population.

EFS was defined as the time from the date of Day 1 (first treatment) + 1 day to the first occurrence of any of the following: Loss of complete hematologic response (CHR), Loss of CCyR, Death from any cause, Progression to the AP or BC of CML, Not achieving CHR up to 3 months (i.e. 91 + 15 days).

Time frame: at 12 months

Population: The intent-to-treat (ITT) population consisted of all patients who received at least one dose of study drug.

Major cytogenetic response (MCyR) parameters were defined as 0 to 35% Philadelphia positive (Ph+) metaphases.

Time frame: 12 and 24 months

Population: The ITT\_CyR population was a subset of the ITT population including the Ph+ patients at screening was considered. Patients who had either no metaphases recorded at screening bone marrow or only negative metaphases recorded at screening bone marrow but had Ph+ metaphases at any visits after screening were also part of this population.

MMR was defined as BCR-ABL ratio (IS) ≤ 0.1% in a peripheral blood sample. BCR-ABL1 is an abnormal gene found in chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL). The chromosomal defect in the Philadelphia chromosome is a translocation, in which parts of two chromosomes, 9 and 22, swap places. The result is that a fusion gene is created by juxtapositioning the Abl1 gene on chromosome 9 to a part of the BCR (breakpoint cluster region) gene on chromosome 22. Depending upon the breakpoints on the BCR gene, there are several forms of fusion proteins.

Time frame: 12 months, 24 months

Population: Intent-to-treat\_Molecular (ITT\_MR) analysis set was a subset of the ITT population including the patients with typical BCR-ABL transcript at screening.

OS was defined as the time between the date of Day 1 (first treatment) and the date of death from any cause. Deaths which occurred after the 24-month time window and which were occasionally reported by some Investigators were excluded from the analysis. This is in agreement with the protocol stating that patients were to be followed for survival and progression to AP/BC up to 24 months after the participants treatment start.

Time frame: 12 months, 24 months

Population: The intent-to-treat (ITT) population consisted of all patients who received at least one dose of study drug.

PFS was defined by the study protocol as the time from the date of start of study drug to the date of earliest progression to AP/BC, or the date of death from any cause.

Time frame: 12 months

Population: The intent-to-treat (ITT) population consisted of all patients who received at least one dose of study drug.

PFS was defined by the study protocol as the time from the date of start of study drug to the date of earliest progression to AP/BC, or the date of death from any cause.

Time frame: 12 months, 24 months

Population: The intent-to-treat (ITT) population consisted of all patients who received at least one dose of study drug.

CHR was defined as all of the following present for ≥ 4 weeks in the peripheral blood: WBC count \< 10 x 109/L, Platelet count \< 450 x 109/L, No circulating peripheral blood blasts, promyelocytes, myelocytes, or metamyelocytes in the peripheral blood, The presence of \< 5% basophils, No evidence of disease-related symptoms and extramedullary disease, including spleen and liver. Loss of CHR was defined as the appearance of any of the following after having achieved a CHR confirmed by a second determination ≥ 4 weeks later (unless associated with progression to AP/BC or death, which was considered to be a confirmed loss of CHR event on its own): WBC count that increased to \> 20.0 x 109/L, Platelet count that increased to ≥ 600 x 109/L, Any palpable spleen, defined as size of spleen below costal margin \> 5 cm, Appearance of \> 5% myelocytes plus metamyelocytes, or any promyelocytes or blasts in the peripheral blood.

Time frame: 12 months, 24 months

Population: The intent-to-treat (ITT) population consisted of all patients who received at least one dose of study drug.

EFS was defined as the time from the date of Day 1 (first treatment) + 1 day to the first occurrence of any of the following: Loss of complete hematologic response (CHR), Loss of CCyR, Death from any cause, Progression to the AP or BC of CML, Not achieving CHR up to 3 months (ie, 91 + 15 days), Not achieving CCyR up to 18 months (ie, 548 + 15 days), whichever is earlier.

Time frame: at 12 and 24 months

Population: The intent-to-treat (ITT) population consisted of all patients who received at least one dose of study drug.

MR4\^0 was defined as either (i) detectable disease ≤ 0.01% BCR-ABL ratio (international scale (IS)) with mean ABL transcripts ≥ 10 000 or (ii) undetectable disease in complementary deoxyribonucleic acid (cDNA) with ≥ 10 000 ABL transcripts.

Time frame: 12 and 24 months

Population: The ITT\_MR population was a subset of the ITT population including the patients with typical BCR-ABL transcript at screening ie, b3a2 and/or b2a2 were considered. This population was referred to as ITT\_MR.

MR4\^0 was defined as either (i) detectable disease ≤ 0.01% BCR-ABL ratio (international scale (IS)) with mean ABL transcripts ≥ 10 000 or (ii) undetectable disease in complementary deoxyribonucleic acid (cDNA) with ≥ 10 000 ABL transcripts. BCR = Breakpoint Cluster Region gene/BCR gene product BCR-ABL is fusion gene formed from the ABL gene from chromosome 9 fusing with the BCR gene on chromosome 22, the gene product is BCR-ABL tyrosine kinase

Time frame: by 18 months

Population: The ITT\_MR population was a subset of the ITT population including the patients with typical BCR-ABL transcript at screening ie, b3a2 and/or b2a2 were considered. This population was referred to as ITT\_MR.

MR4\^5 was defined as either (i) detectable disease ≤ 0.0032% BCR-ABL ratio (IS) with mean ABL transcripts ≥ 32 000 or (ii) undetectable disease in cDNA with ≥ 32 000 ABL transcripts).

Time frame: 12 and 24 months

Population: The ITT\_MR population was a subset of the ITT population including the patients with typical BCR-ABL transcript at screening ie, b3a2 and/or b2a2 were considered.

MR4\^5 was defined as either (i) detectable disease ≤ 0.0032% BCR-ABL ratio (IS) with mean ABL transcripts ≥ 32 000 or (ii) undetectable disease in cDNA with ≥ 32 000 ABL transcripts). BCR = Breakpoint Cluster Region gene/BCR gene product BCR-ABL is fusion gene formed from the ABL gene from chromosome 9 fusing with the BCR gene on chromosome 22, the gene product is BCR-ABL tyrosine kinase

Time frame: by 18 months

Population: The ITT\_MR population was a subset of the ITT population including the patients with typical BCR-ABL transcript at screening ie, b3a2 and/or b2a2 were considered.