HALVING TIME AND LOG REDUCTION ARE GOOD PREDICTORS OF OPTIMAL MOLECULAR RESPONSE IN CHRONIC MYELOID LEUKEMIA PATIENTS WITH SUB-OPTIMAL RESPONSE AT 3 MONTHS
(Abstract release date: 05/19/16)
EHA Library. Santos M. 06/09/16; 134716; PB1816
Ms. Maria João Santos
Contributions
Contributions
Abstract
Abstract: PB1816
Type: Publication Only
Background
In Chronic Myeloid Leukemia (CML) the 3-month molecular evaluation defines suboptimal responders with BCR-ABL1>10%. This group shows worse prognosis and is thought to benefit from treatment change to 2nd-line TKIs in an early onset. Nonetheless, some patients respond favorably long-term without treatment change. The decline rate of the BCR-ABL1, measured at 3M of treatment, may distinguish patients with suboptimal response that will achieve good responses from those who will need therapy switch.
Aims
In a group of CML patients, analyze clinical and laboratorial differences between patients with optimal/sub-optimal response, after 3M of Imatinib. To determine the predictive value of halving time and log reduction for optimal molecular response at 6 and 12M in patients with suboptimal response.
Methods
Single center retrospective analysis of 24 CP-CML patients treated with Imatinib 1st-line. Halving time at 3M of treatment calculated according to the formula proposed by Branford et al (2014), c=-ln(2)/k, c is the halving time, k (k=[ln(b)-ln(a)]/d) the reduction in BCR-ABL1 transcript between initial (a) and 3M quantification (b), divided by the number of days (d) between the two evaluations. Log reduction (log(a/b)) calculated at 3M of treatment, a is the 3M QPCR value and b the baseline value.Descriptive statistic analysis performed using the SPSS (v.21). The predictive value was calculated through the area under the curve (AUC), using MedCal statistical program. The optimal cut-offs were calculated using the Younden (J) Index.
Results
Between January 2006 and August 2014, 24 patients were diagnosed with CP-CML and started on Imatinib 400mg id; 16 male (66,7%) and 8 female (33,3%), median age=57,71 years(±15,75). Clinical-laboratory findings at diagnosis: mean Hb=12,42g/dL (±1,81;), Plts=452,92x103/uL (±299,51), median Leuc=75,1x103/uL (141), mean peripheral basophil percentage=2,43%(±1,8) and peripheral blasts=2,3% (±2,07); mean LDH=1302,79U/L (±852,41); mean palpable spleen size=13cm (±5,97). Sokal and EUTOS scores were obtained for 21/24 patients (Sokal score: 3 (14,3%) low-risk; 9 (42,9%) intermediate-risk; 9 (42,9%) high-risk. EUTOS score: 19 (90,5%) low-risk; 2 (9,5%) high-risk). The mean time between initial and 3M QPCR evaluation was 93,25 days (±18,43). At 3M, 14 patients (48,3%) had optimal and 10 (41,7%) suboptimal response. Transcript level at baseline was significantly higher in the suboptimal group (127,3±70,62 vs 73,53±25,5;p=0,04).In the suboptimal group, the halving time was highly predictive of optimal molecular response at 6M (AUC=0,93;p<0,0001), as well as response failure (AUC=0,83;p=0,02). The log reduction was highly predictive of optimal molecular response at 6M (AUC=0,96; p<0,0001), at 12M (AUC=0,83;p=0,03) and for response failure at 12M (AUC=0,85;p=0,01). The most predictive cut-off values (J) for halving time and log reduction were obtained for the 6M optimal response (J=0,87). A halving time of 22,59 days and a -1,1 log reduction were predictors of optimal molecular response at 6M.
Conclusion
In this group, patients with suboptimal response at 3M had a significantly higher BCR-ABL1 transcript at baseline. A halving time of 22,59 days and a -1,1 log reduction predicted optimal molecular response at 6M. In an early time-point of molecular evaluation, the use of parameters evaluating kinetics of the transcript decline will contribute to discriminate patients outcome and guide treatment options.
Session topic: E-poster
Keyword(s): Chronic myeloid leukemia
Type: Publication Only
Background
In Chronic Myeloid Leukemia (CML) the 3-month molecular evaluation defines suboptimal responders with BCR-ABL1>10%. This group shows worse prognosis and is thought to benefit from treatment change to 2nd-line TKIs in an early onset. Nonetheless, some patients respond favorably long-term without treatment change. The decline rate of the BCR-ABL1, measured at 3M of treatment, may distinguish patients with suboptimal response that will achieve good responses from those who will need therapy switch.
Aims
In a group of CML patients, analyze clinical and laboratorial differences between patients with optimal/sub-optimal response, after 3M of Imatinib. To determine the predictive value of halving time and log reduction for optimal molecular response at 6 and 12M in patients with suboptimal response.
Methods
Single center retrospective analysis of 24 CP-CML patients treated with Imatinib 1st-line. Halving time at 3M of treatment calculated according to the formula proposed by Branford et al (2014), c=-ln(2)/k, c is the halving time, k (k=[ln(b)-ln(a)]/d) the reduction in BCR-ABL1 transcript between initial (a) and 3M quantification (b), divided by the number of days (d) between the two evaluations. Log reduction (log(a/b)) calculated at 3M of treatment, a is the 3M QPCR value and b the baseline value.Descriptive statistic analysis performed using the SPSS (v.21). The predictive value was calculated through the area under the curve (AUC), using MedCal statistical program. The optimal cut-offs were calculated using the Younden (J) Index.
Results
Between January 2006 and August 2014, 24 patients were diagnosed with CP-CML and started on Imatinib 400mg id; 16 male (66,7%) and 8 female (33,3%), median age=57,71 years(±15,75). Clinical-laboratory findings at diagnosis: mean Hb=12,42g/dL (±1,81;), Plts=452,92x103/uL (±299,51), median Leuc=75,1x103/uL (141), mean peripheral basophil percentage=2,43%(±1,8) and peripheral blasts=2,3% (±2,07); mean LDH=1302,79U/L (±852,41); mean palpable spleen size=13cm (±5,97). Sokal and EUTOS scores were obtained for 21/24 patients (Sokal score: 3 (14,3%) low-risk; 9 (42,9%) intermediate-risk; 9 (42,9%) high-risk. EUTOS score: 19 (90,5%) low-risk; 2 (9,5%) high-risk). The mean time between initial and 3M QPCR evaluation was 93,25 days (±18,43). At 3M, 14 patients (48,3%) had optimal and 10 (41,7%) suboptimal response. Transcript level at baseline was significantly higher in the suboptimal group (127,3±70,62 vs 73,53±25,5;p=0,04).In the suboptimal group, the halving time was highly predictive of optimal molecular response at 6M (AUC=0,93;p<0,0001), as well as response failure (AUC=0,83;p=0,02). The log reduction was highly predictive of optimal molecular response at 6M (AUC=0,96; p<0,0001), at 12M (AUC=0,83;p=0,03) and for response failure at 12M (AUC=0,85;p=0,01). The most predictive cut-off values (J) for halving time and log reduction were obtained for the 6M optimal response (J=0,87). A halving time of 22,59 days and a -1,1 log reduction were predictors of optimal molecular response at 6M.
Conclusion
In this group, patients with suboptimal response at 3M had a significantly higher BCR-ABL1 transcript at baseline. A halving time of 22,59 days and a -1,1 log reduction predicted optimal molecular response at 6M. In an early time-point of molecular evaluation, the use of parameters evaluating kinetics of the transcript decline will contribute to discriminate patients outcome and guide treatment options.
Session topic: E-poster
Keyword(s): Chronic myeloid leukemia
Abstract: PB1816
Type: Publication Only
Background
In Chronic Myeloid Leukemia (CML) the 3-month molecular evaluation defines suboptimal responders with BCR-ABL1>10%. This group shows worse prognosis and is thought to benefit from treatment change to 2nd-line TKIs in an early onset. Nonetheless, some patients respond favorably long-term without treatment change. The decline rate of the BCR-ABL1, measured at 3M of treatment, may distinguish patients with suboptimal response that will achieve good responses from those who will need therapy switch.
Aims
In a group of CML patients, analyze clinical and laboratorial differences between patients with optimal/sub-optimal response, after 3M of Imatinib. To determine the predictive value of halving time and log reduction for optimal molecular response at 6 and 12M in patients with suboptimal response.
Methods
Single center retrospective analysis of 24 CP-CML patients treated with Imatinib 1st-line. Halving time at 3M of treatment calculated according to the formula proposed by Branford et al (2014), c=-ln(2)/k, c is the halving time, k (k=[ln(b)-ln(a)]/d) the reduction in BCR-ABL1 transcript between initial (a) and 3M quantification (b), divided by the number of days (d) between the two evaluations. Log reduction (log(a/b)) calculated at 3M of treatment, a is the 3M QPCR value and b the baseline value.Descriptive statistic analysis performed using the SPSS (v.21). The predictive value was calculated through the area under the curve (AUC), using MedCal statistical program. The optimal cut-offs were calculated using the Younden (J) Index.
Results
Between January 2006 and August 2014, 24 patients were diagnosed with CP-CML and started on Imatinib 400mg id; 16 male (66,7%) and 8 female (33,3%), median age=57,71 years(±15,75). Clinical-laboratory findings at diagnosis: mean Hb=12,42g/dL (±1,81;), Plts=452,92x103/uL (±299,51), median Leuc=75,1x103/uL (141), mean peripheral basophil percentage=2,43%(±1,8) and peripheral blasts=2,3% (±2,07); mean LDH=1302,79U/L (±852,41); mean palpable spleen size=13cm (±5,97). Sokal and EUTOS scores were obtained for 21/24 patients (Sokal score: 3 (14,3%) low-risk; 9 (42,9%) intermediate-risk; 9 (42,9%) high-risk. EUTOS score: 19 (90,5%) low-risk; 2 (9,5%) high-risk). The mean time between initial and 3M QPCR evaluation was 93,25 days (±18,43). At 3M, 14 patients (48,3%) had optimal and 10 (41,7%) suboptimal response. Transcript level at baseline was significantly higher in the suboptimal group (127,3±70,62 vs 73,53±25,5;p=0,04).In the suboptimal group, the halving time was highly predictive of optimal molecular response at 6M (AUC=0,93;p<0,0001), as well as response failure (AUC=0,83;p=0,02). The log reduction was highly predictive of optimal molecular response at 6M (AUC=0,96; p<0,0001), at 12M (AUC=0,83;p=0,03) and for response failure at 12M (AUC=0,85;p=0,01). The most predictive cut-off values (J) for halving time and log reduction were obtained for the 6M optimal response (J=0,87). A halving time of 22,59 days and a -1,1 log reduction were predictors of optimal molecular response at 6M.
Conclusion
In this group, patients with suboptimal response at 3M had a significantly higher BCR-ABL1 transcript at baseline. A halving time of 22,59 days and a -1,1 log reduction predicted optimal molecular response at 6M. In an early time-point of molecular evaluation, the use of parameters evaluating kinetics of the transcript decline will contribute to discriminate patients outcome and guide treatment options.
Session topic: E-poster
Keyword(s): Chronic myeloid leukemia
Type: Publication Only
Background
In Chronic Myeloid Leukemia (CML) the 3-month molecular evaluation defines suboptimal responders with BCR-ABL1>10%. This group shows worse prognosis and is thought to benefit from treatment change to 2nd-line TKIs in an early onset. Nonetheless, some patients respond favorably long-term without treatment change. The decline rate of the BCR-ABL1, measured at 3M of treatment, may distinguish patients with suboptimal response that will achieve good responses from those who will need therapy switch.
Aims
In a group of CML patients, analyze clinical and laboratorial differences between patients with optimal/sub-optimal response, after 3M of Imatinib. To determine the predictive value of halving time and log reduction for optimal molecular response at 6 and 12M in patients with suboptimal response.
Methods
Single center retrospective analysis of 24 CP-CML patients treated with Imatinib 1st-line. Halving time at 3M of treatment calculated according to the formula proposed by Branford et al (2014), c=-ln(2)/k, c is the halving time, k (k=[ln(b)-ln(a)]/d) the reduction in BCR-ABL1 transcript between initial (a) and 3M quantification (b), divided by the number of days (d) between the two evaluations. Log reduction (log(a/b)) calculated at 3M of treatment, a is the 3M QPCR value and b the baseline value.Descriptive statistic analysis performed using the SPSS (v.21). The predictive value was calculated through the area under the curve (AUC), using MedCal statistical program. The optimal cut-offs were calculated using the Younden (J) Index.
Results
Between January 2006 and August 2014, 24 patients were diagnosed with CP-CML and started on Imatinib 400mg id; 16 male (66,7%) and 8 female (33,3%), median age=57,71 years(±15,75). Clinical-laboratory findings at diagnosis: mean Hb=12,42g/dL (±1,81;), Plts=452,92x103/uL (±299,51), median Leuc=75,1x103/uL (141), mean peripheral basophil percentage=2,43%(±1,8) and peripheral blasts=2,3% (±2,07); mean LDH=1302,79U/L (±852,41); mean palpable spleen size=13cm (±5,97). Sokal and EUTOS scores were obtained for 21/24 patients (Sokal score: 3 (14,3%) low-risk; 9 (42,9%) intermediate-risk; 9 (42,9%) high-risk. EUTOS score: 19 (90,5%) low-risk; 2 (9,5%) high-risk). The mean time between initial and 3M QPCR evaluation was 93,25 days (±18,43). At 3M, 14 patients (48,3%) had optimal and 10 (41,7%) suboptimal response. Transcript level at baseline was significantly higher in the suboptimal group (127,3±70,62 vs 73,53±25,5;p=0,04).In the suboptimal group, the halving time was highly predictive of optimal molecular response at 6M (AUC=0,93;p<0,0001), as well as response failure (AUC=0,83;p=0,02). The log reduction was highly predictive of optimal molecular response at 6M (AUC=0,96; p<0,0001), at 12M (AUC=0,83;p=0,03) and for response failure at 12M (AUC=0,85;p=0,01). The most predictive cut-off values (J) for halving time and log reduction were obtained for the 6M optimal response (J=0,87). A halving time of 22,59 days and a -1,1 log reduction were predictors of optimal molecular response at 6M.
Conclusion
In this group, patients with suboptimal response at 3M had a significantly higher BCR-ABL1 transcript at baseline. A halving time of 22,59 days and a -1,1 log reduction predicted optimal molecular response at 6M. In an early time-point of molecular evaluation, the use of parameters evaluating kinetics of the transcript decline will contribute to discriminate patients outcome and guide treatment options.
Session topic: E-poster
Keyword(s): Chronic myeloid leukemia
{{ help_message }}
{{filter}}