LOW DOSE DASATINIB TREATMENT IN ELDERLY CML PATIENTS
(Abstract release date: 05/19/16)
EHA Library. Sano H. 06/09/16; 134737; PB1837
Dr. Haruhiko Sano
Contributions
Contributions
Abstract
Abstract: PB1837
Type: Publication Only
Background
Clinical outcomes and survival of chronic myeloid leukemia (CML) patients treated with ABL tyrosine kinase inhibitors (TKIs) have significantly improved. To achieve a good prognosis, including cessation of TKI treatment, a rapid and deep response to TKIs is important. Elderly patients usually cannot receive the standard dose (100mg QD) of dasatinib because of its adverse effects (AE). Nevertheless, several elderly patients achieve a deep response to very low doses of ABL TKIs.
Aims
We retrospectively analyzed the efficiency of low dose dasatinib in elderly patients with CML.
Methods
We retrospectively evaluated imatinib-resistant and -intolerant CML-CP patients aged 65 or over who had been administrated less than 100mg QD dasatinib between 2010 and 2015 at Saga University Hospital. We estimated therapeutic efficiencies based on bcr-abl mRNA levels measured by RQ-PCR compensated according to international scale (IS) and/or TMA (transcription mediated amplification) method for peripheral blood. In the TMA method, undetectable is considered to be the same as a 4-log reduction (MR4) of RQ-PCR on the IS. In addition to efficacy, adverse effects at lower doses of dasatinib were also investigated.
Results
Twenty-one elderly CML-CP patients were investigated. Sixteen patients (76.2%) were newly diagnosed. The median age at diagnosis was 72 years old (range, 65–83). Thirty-three per cent were male, and the median follow up time was 20.5 months (range, 4–56). The mean dose of dasatinib was 24.6 mg. The numbers of patients receiving a mean dasatinib dose of 50mg or less and 20mg or less were 19 (90.4 %) and 15 (71.4 %), respectively. Twenty patients (95.2 %) and 16 patients (76.2 %) achieved a major molecular response (MMR) and a MR4, respectively. In addition, 10 patients (47.6 %) achieved a MR4.5. The median durations of dasatinib treatment to achieve a MMR and an MR4 were 6 months (range; 2–11) and 12 months (range; 3–50), respectively. All cases achieved a complete cytogenetic response (CCyR) within 12 months.In the case of the 15 patients receiving a mean dose of 20 mg or less, 14 patients (93.3 %) achieved a MMR and 11 patients (73.3 %) achieved a MR4. The median durations of MMR and MR4 were 6 months (range, 3–10) and 9.5 months (range, 3–38), respectively. Additionally, 13 patients treated with a dose of 20mg or less as first line therapy. MMR and MR4 were achieved in 84.6 % and 69.2 %, respectively. 53.8 % achieved a MR4.5. The median durations of MMR and MR4 were 6 months (range, 3–11) and 10 months (range; 4–38), respectively, in this cohort. The main AE was plural effusion (6 patients; 28.5 %). Surprisingly, HBV reactivation occurred in 2 patients treated with 20 mg QD. Except for 1 patient who changed to another TKI because of gastrointestinal bleeding, most AEs became tolerable after dose reduction. Seven patients administered 50 mg or less had increased large granular lymphocyte counts.
Conclusion
Treatment with dasatinib at lower than standard doses was well tolerated and resulted in an adequate molecular response in elderly CML patients without causing severe AEs. Thus, prospective studies should be performed to determine the effects of administering lower doses of dasatinib to elderly CML-CP patients.
Session topic: E-poster
Keyword(s): Chronic myeloid leukemia, Elderly, Tyrosine kinase inhibitor
Type: Publication Only
Background
Clinical outcomes and survival of chronic myeloid leukemia (CML) patients treated with ABL tyrosine kinase inhibitors (TKIs) have significantly improved. To achieve a good prognosis, including cessation of TKI treatment, a rapid and deep response to TKIs is important. Elderly patients usually cannot receive the standard dose (100mg QD) of dasatinib because of its adverse effects (AE). Nevertheless, several elderly patients achieve a deep response to very low doses of ABL TKIs.
Aims
We retrospectively analyzed the efficiency of low dose dasatinib in elderly patients with CML.
Methods
We retrospectively evaluated imatinib-resistant and -intolerant CML-CP patients aged 65 or over who had been administrated less than 100mg QD dasatinib between 2010 and 2015 at Saga University Hospital. We estimated therapeutic efficiencies based on bcr-abl mRNA levels measured by RQ-PCR compensated according to international scale (IS) and/or TMA (transcription mediated amplification) method for peripheral blood. In the TMA method, undetectable is considered to be the same as a 4-log reduction (MR4) of RQ-PCR on the IS. In addition to efficacy, adverse effects at lower doses of dasatinib were also investigated.
Results
Twenty-one elderly CML-CP patients were investigated. Sixteen patients (76.2%) were newly diagnosed. The median age at diagnosis was 72 years old (range, 65–83). Thirty-three per cent were male, and the median follow up time was 20.5 months (range, 4–56). The mean dose of dasatinib was 24.6 mg. The numbers of patients receiving a mean dasatinib dose of 50mg or less and 20mg or less were 19 (90.4 %) and 15 (71.4 %), respectively. Twenty patients (95.2 %) and 16 patients (76.2 %) achieved a major molecular response (MMR) and a MR4, respectively. In addition, 10 patients (47.6 %) achieved a MR4.5. The median durations of dasatinib treatment to achieve a MMR and an MR4 were 6 months (range; 2–11) and 12 months (range; 3–50), respectively. All cases achieved a complete cytogenetic response (CCyR) within 12 months.In the case of the 15 patients receiving a mean dose of 20 mg or less, 14 patients (93.3 %) achieved a MMR and 11 patients (73.3 %) achieved a MR4. The median durations of MMR and MR4 were 6 months (range, 3–10) and 9.5 months (range, 3–38), respectively. Additionally, 13 patients treated with a dose of 20mg or less as first line therapy. MMR and MR4 were achieved in 84.6 % and 69.2 %, respectively. 53.8 % achieved a MR4.5. The median durations of MMR and MR4 were 6 months (range, 3–11) and 10 months (range; 4–38), respectively, in this cohort. The main AE was plural effusion (6 patients; 28.5 %). Surprisingly, HBV reactivation occurred in 2 patients treated with 20 mg QD. Except for 1 patient who changed to another TKI because of gastrointestinal bleeding, most AEs became tolerable after dose reduction. Seven patients administered 50 mg or less had increased large granular lymphocyte counts.
Conclusion
Treatment with dasatinib at lower than standard doses was well tolerated and resulted in an adequate molecular response in elderly CML patients without causing severe AEs. Thus, prospective studies should be performed to determine the effects of administering lower doses of dasatinib to elderly CML-CP patients.
Session topic: E-poster
Keyword(s): Chronic myeloid leukemia, Elderly, Tyrosine kinase inhibitor
Abstract: PB1837
Type: Publication Only
Background
Clinical outcomes and survival of chronic myeloid leukemia (CML) patients treated with ABL tyrosine kinase inhibitors (TKIs) have significantly improved. To achieve a good prognosis, including cessation of TKI treatment, a rapid and deep response to TKIs is important. Elderly patients usually cannot receive the standard dose (100mg QD) of dasatinib because of its adverse effects (AE). Nevertheless, several elderly patients achieve a deep response to very low doses of ABL TKIs.
Aims
We retrospectively analyzed the efficiency of low dose dasatinib in elderly patients with CML.
Methods
We retrospectively evaluated imatinib-resistant and -intolerant CML-CP patients aged 65 or over who had been administrated less than 100mg QD dasatinib between 2010 and 2015 at Saga University Hospital. We estimated therapeutic efficiencies based on bcr-abl mRNA levels measured by RQ-PCR compensated according to international scale (IS) and/or TMA (transcription mediated amplification) method for peripheral blood. In the TMA method, undetectable is considered to be the same as a 4-log reduction (MR4) of RQ-PCR on the IS. In addition to efficacy, adverse effects at lower doses of dasatinib were also investigated.
Results
Twenty-one elderly CML-CP patients were investigated. Sixteen patients (76.2%) were newly diagnosed. The median age at diagnosis was 72 years old (range, 65–83). Thirty-three per cent were male, and the median follow up time was 20.5 months (range, 4–56). The mean dose of dasatinib was 24.6 mg. The numbers of patients receiving a mean dasatinib dose of 50mg or less and 20mg or less were 19 (90.4 %) and 15 (71.4 %), respectively. Twenty patients (95.2 %) and 16 patients (76.2 %) achieved a major molecular response (MMR) and a MR4, respectively. In addition, 10 patients (47.6 %) achieved a MR4.5. The median durations of dasatinib treatment to achieve a MMR and an MR4 were 6 months (range; 2–11) and 12 months (range; 3–50), respectively. All cases achieved a complete cytogenetic response (CCyR) within 12 months.In the case of the 15 patients receiving a mean dose of 20 mg or less, 14 patients (93.3 %) achieved a MMR and 11 patients (73.3 %) achieved a MR4. The median durations of MMR and MR4 were 6 months (range, 3–10) and 9.5 months (range, 3–38), respectively. Additionally, 13 patients treated with a dose of 20mg or less as first line therapy. MMR and MR4 were achieved in 84.6 % and 69.2 %, respectively. 53.8 % achieved a MR4.5. The median durations of MMR and MR4 were 6 months (range, 3–11) and 10 months (range; 4–38), respectively, in this cohort. The main AE was plural effusion (6 patients; 28.5 %). Surprisingly, HBV reactivation occurred in 2 patients treated with 20 mg QD. Except for 1 patient who changed to another TKI because of gastrointestinal bleeding, most AEs became tolerable after dose reduction. Seven patients administered 50 mg or less had increased large granular lymphocyte counts.
Conclusion
Treatment with dasatinib at lower than standard doses was well tolerated and resulted in an adequate molecular response in elderly CML patients without causing severe AEs. Thus, prospective studies should be performed to determine the effects of administering lower doses of dasatinib to elderly CML-CP patients.
Session topic: E-poster
Keyword(s): Chronic myeloid leukemia, Elderly, Tyrosine kinase inhibitor
Type: Publication Only
Background
Clinical outcomes and survival of chronic myeloid leukemia (CML) patients treated with ABL tyrosine kinase inhibitors (TKIs) have significantly improved. To achieve a good prognosis, including cessation of TKI treatment, a rapid and deep response to TKIs is important. Elderly patients usually cannot receive the standard dose (100mg QD) of dasatinib because of its adverse effects (AE). Nevertheless, several elderly patients achieve a deep response to very low doses of ABL TKIs.
Aims
We retrospectively analyzed the efficiency of low dose dasatinib in elderly patients with CML.
Methods
We retrospectively evaluated imatinib-resistant and -intolerant CML-CP patients aged 65 or over who had been administrated less than 100mg QD dasatinib between 2010 and 2015 at Saga University Hospital. We estimated therapeutic efficiencies based on bcr-abl mRNA levels measured by RQ-PCR compensated according to international scale (IS) and/or TMA (transcription mediated amplification) method for peripheral blood. In the TMA method, undetectable is considered to be the same as a 4-log reduction (MR4) of RQ-PCR on the IS. In addition to efficacy, adverse effects at lower doses of dasatinib were also investigated.
Results
Twenty-one elderly CML-CP patients were investigated. Sixteen patients (76.2%) were newly diagnosed. The median age at diagnosis was 72 years old (range, 65–83). Thirty-three per cent were male, and the median follow up time was 20.5 months (range, 4–56). The mean dose of dasatinib was 24.6 mg. The numbers of patients receiving a mean dasatinib dose of 50mg or less and 20mg or less were 19 (90.4 %) and 15 (71.4 %), respectively. Twenty patients (95.2 %) and 16 patients (76.2 %) achieved a major molecular response (MMR) and a MR4, respectively. In addition, 10 patients (47.6 %) achieved a MR4.5. The median durations of dasatinib treatment to achieve a MMR and an MR4 were 6 months (range; 2–11) and 12 months (range; 3–50), respectively. All cases achieved a complete cytogenetic response (CCyR) within 12 months.In the case of the 15 patients receiving a mean dose of 20 mg or less, 14 patients (93.3 %) achieved a MMR and 11 patients (73.3 %) achieved a MR4. The median durations of MMR and MR4 were 6 months (range, 3–10) and 9.5 months (range, 3–38), respectively. Additionally, 13 patients treated with a dose of 20mg or less as first line therapy. MMR and MR4 were achieved in 84.6 % and 69.2 %, respectively. 53.8 % achieved a MR4.5. The median durations of MMR and MR4 were 6 months (range, 3–11) and 10 months (range; 4–38), respectively, in this cohort. The main AE was plural effusion (6 patients; 28.5 %). Surprisingly, HBV reactivation occurred in 2 patients treated with 20 mg QD. Except for 1 patient who changed to another TKI because of gastrointestinal bleeding, most AEs became tolerable after dose reduction. Seven patients administered 50 mg or less had increased large granular lymphocyte counts.
Conclusion
Treatment with dasatinib at lower than standard doses was well tolerated and resulted in an adequate molecular response in elderly CML patients without causing severe AEs. Thus, prospective studies should be performed to determine the effects of administering lower doses of dasatinib to elderly CML-CP patients.
Session topic: E-poster
Keyword(s): Chronic myeloid leukemia, Elderly, Tyrosine kinase inhibitor
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