Contributions
Abstract: PB1923
Type: Publication Only
Background
In CML-CP, Imatinib remains the drug of choice for frontline therapy in resource constrained countries, despite newer Tyrosine Kinase Inhibitors. However, Nilotinib/Dasatinib although costlier, have the advantage of earlier and deeper molecular responses. Giving Nilotinib for the first 3 months and then switching to Imatinib to capitalise on the quicker and deeper responses without adding substantially to the cost of treatment has never been studied before.
Aims
To compare the molecular responses and long term outcomes in treatment naïve CML-CP patients treated with Nilotinib for the initial 3 months followed by Imatinib compared to treatment with Imatinib upfront.
Methods
Newly diagnosed treatment naïve CML –CP patients affording therapy, who gave consent were included in the study. Accelerated phase/blast crisis patients were excluded. Patients were divided into 2 groups. Group 1 received Imatinib 400 OD upfront. Group 2 received Nilotinib 300BD for 1st 3 months and then were switched over to Imatinib 400 OD after 3 months. Clinical and lab follow up with complte blood counts and quantitative RT-PCR for Bcr-abl was done at 3, 6 and 12 months.
Results
21 patients in group 1 and 18 patients in Group 2 were enrolled and followed up. Mean age was 37.4 and 38.16 yrs respectively. Group 2 had more males than group 1 (77.77% vs 33.33%, p value 0.006). Sokal score profile was not statistically different in both the groups (low risk: 33.33%vs 22.22%, intermediate risk: 28% vs 44.44%, high risk: 38% vs 33.33%). The mean RQPCR for bcr-abl was significantly higher at 3 months in patients in Group 1 compared to Group 2 (Table 1). A warning response was also more common in Group 1. The 6 and 12 month responses were however not significantly different in both the groups. In Group 2, there were 5 patients (1 Sokal low, 3 intermediate and 1 high risk) who achieved optimal response at 3 months, however had loss of response at 6 months (3) and 12 months (2). Only 1 patient on Imatinib had loss of respose at 6 months.
Table 1: RQPCR for bcr abl at various time points in both groups
| 3 months | 6 months | 12 months | ||||||
| Group 1 | Group 2 | P | Group 1 | Group 2 | P | Group 1 | Group 2 | P |
N (data available for) | 18 | 17 |
| 16 | 16 |
| 9 | 13 |
|
Mean | 21.67 | 2.424 | 0.018 | 2.182 | 3.703 | 0.47 | 1.333 | 3.05 | 0.5745 |
>10% | 6 | 0 | 0.01 | 2 | 3 | 0.63 | 0 | 1 | 0.48 |
>1 to 9.99 % | 9 | 9 | 0.86 | 3 | 4 | 0.67 | 2 | 2 | 0.49 |
>0.1 to 0.99% | 3 | 5 | 0.37 | 4 | 4 | 0 | 0 | 3 | 0.20 |
<0.1% | 0 | 3 | 0.06 | 7 | 5 | 0.47 | 7 | 7 | 0.07 |
AP/BC | 1 (AP) | 1 (BC) |
| 0 | 0 |
| 0 | 0 |
|
Conclusion
Nilotinib shows significantly better responses than Imatinib at 3 months. This early advantage with Nilotinib is not sustained over time with both groups having similar responses at 6 and 12 months. Furthermore, patients may lose the initial reposnse on Nilotinib and progress when switched to Imatinib. However achieving early molecular responses almost always results in good long term outcomes. Thus the duration of Nilotinib may have to be increased to benefit the majority of the patients before switching over to Imatinib.
Session topic: 8. Chronic myeloid leukemia - Clinical
Keyword(s): Chronic myeloid leukemia, imatinib, Nilotinib
Abstract: PB1923
Type: Publication Only
Background
In CML-CP, Imatinib remains the drug of choice for frontline therapy in resource constrained countries, despite newer Tyrosine Kinase Inhibitors. However, Nilotinib/Dasatinib although costlier, have the advantage of earlier and deeper molecular responses. Giving Nilotinib for the first 3 months and then switching to Imatinib to capitalise on the quicker and deeper responses without adding substantially to the cost of treatment has never been studied before.
Aims
To compare the molecular responses and long term outcomes in treatment naïve CML-CP patients treated with Nilotinib for the initial 3 months followed by Imatinib compared to treatment with Imatinib upfront.
Methods
Newly diagnosed treatment naïve CML –CP patients affording therapy, who gave consent were included in the study. Accelerated phase/blast crisis patients were excluded. Patients were divided into 2 groups. Group 1 received Imatinib 400 OD upfront. Group 2 received Nilotinib 300BD for 1st 3 months and then were switched over to Imatinib 400 OD after 3 months. Clinical and lab follow up with complte blood counts and quantitative RT-PCR for Bcr-abl was done at 3, 6 and 12 months.
Results
21 patients in group 1 and 18 patients in Group 2 were enrolled and followed up. Mean age was 37.4 and 38.16 yrs respectively. Group 2 had more males than group 1 (77.77% vs 33.33%, p value 0.006). Sokal score profile was not statistically different in both the groups (low risk: 33.33%vs 22.22%, intermediate risk: 28% vs 44.44%, high risk: 38% vs 33.33%). The mean RQPCR for bcr-abl was significantly higher at 3 months in patients in Group 1 compared to Group 2 (Table 1). A warning response was also more common in Group 1. The 6 and 12 month responses were however not significantly different in both the groups. In Group 2, there were 5 patients (1 Sokal low, 3 intermediate and 1 high risk) who achieved optimal response at 3 months, however had loss of response at 6 months (3) and 12 months (2). Only 1 patient on Imatinib had loss of respose at 6 months.
Table 1: RQPCR for bcr abl at various time points in both groups
| 3 months | 6 months | 12 months | ||||||
| Group 1 | Group 2 | P | Group 1 | Group 2 | P | Group 1 | Group 2 | P |
N (data available for) | 18 | 17 |
| 16 | 16 |
| 9 | 13 |
|
Mean | 21.67 | 2.424 | 0.018 | 2.182 | 3.703 | 0.47 | 1.333 | 3.05 | 0.5745 |
>10% | 6 | 0 | 0.01 | 2 | 3 | 0.63 | 0 | 1 | 0.48 |
>1 to 9.99 % | 9 | 9 | 0.86 | 3 | 4 | 0.67 | 2 | 2 | 0.49 |
>0.1 to 0.99% | 3 | 5 | 0.37 | 4 | 4 | 0 | 0 | 3 | 0.20 |
<0.1% | 0 | 3 | 0.06 | 7 | 5 | 0.47 | 7 | 7 | 0.07 |
AP/BC | 1 (AP) | 1 (BC) |
| 0 | 0 |
| 0 | 0 |
|
Conclusion
Nilotinib shows significantly better responses than Imatinib at 3 months. This early advantage with Nilotinib is not sustained over time with both groups having similar responses at 6 and 12 months. Furthermore, patients may lose the initial reposnse on Nilotinib and progress when switched to Imatinib. However achieving early molecular responses almost always results in good long term outcomes. Thus the duration of Nilotinib may have to be increased to benefit the majority of the patients before switching over to Imatinib.
Session topic: 8. Chronic myeloid leukemia - Clinical
Keyword(s): Chronic myeloid leukemia, imatinib, Nilotinib