TYROSINE KINASE INHIBITORS IN PHILADELPHIA-CHROMOSOME POSITIVE ADULT ACUTE LYMPHOBLASTIC LEUKEMIA IN REAL CLINICAL PRACTICE
(Abstract release date: 05/19/16)
EHA Library. Folber F. 06/09/16; 132425; E876
Dr. Frantisek Folber
Contributions
Contributions
Abstract
Abstract: E876
Type: Eposter Presentation
Background
Adult patients with Philadelphia-chromosome positive acute lymphoblastic leukemia (Ph+ ALL) are at high risk of relapse. Allogeneic stem cell transplantation still remains the treatment of choice in spite of the major benefit brought by adding tyrosine kinase inhibitors (TKIs) to the standard chemotherapy. On the other side, TKIs also bear several side effects and some of them require significant dose reductions.
Aims
The aim of this analysis was to focus on treatment strategies in unselected adult Ph+ ALL patients in real clinical practice and how TKI dose reduction may influence their outcomes.
Methods
All adult patients diagnosed with Ph+ ALL and treated with TKIs at our centre between 2005 and 2015 were included into this retrospective analysis. We describe baseline features, treatment options and outcomes. The data were analysed for response and relapse rates and factors affecting survival.
Results
A total number of 41 consecutive patients aged 19 to 82 years (median 58) at the time of diagnosis of Ph+ ALL were included. Leukocyte count was 1.8 to 296 x 109/L (median 20) at presentation. Most commonly observed were common-B immunophenotype (73%) and p190 bcr-abl transcript (63%). Thirteen (32%) patients were treated according to pediatric-based intensive protocol, 13 (32%) using a reduced-toxicity protocol, and 15 (37%) in a palliative approach. An allogeneic transplant was performed in 17 (41%) patients. Thirty-three (85%) patients achieved a complete remission (CR) and 56% of them achieved a complete molecular response (CMR). First line TKI was imatinib in all patients, with a median daily dose of 600mg. In 18 (44%) patients the dose had to be reduced to 400, 300 or 200mg due to side effects (haematological 36%, oedemas 32%, gastrointestinal 16%, skin rash 4%). Sixteen (46%) patients in CR eventually relapsed and only 6 (38%) achieved a second CR. Second line TKI was dasatinib (12; 75%) or 800mg imatinib (3; 19%). Dasatinib was given at a median daily dose of 140mg but in a much broader range (35 to 140 mg). This dose was further decreased in 10 (83%) patients, while most common non-haematological side effects were gastrointestinal (17%), oedemas (13%) and effusion (4%). Five (83%) of these patients in CR2 experienced a second relapse. During the follow-up with a median of 12 months (range 1 to 103 months), 27 (66%) patients died; fifteen (56%) of infection, 11 (41%) of disease progression and one (4 %) of a secondary malignancy. Fourteen (34%) patients are still alive in complete remission. Five-year overall survival (OS) in the whole cohort was 30%. The survival was not influenced by leukocyte count, immunophenotype nor the type of the bcr-abl transcript. The statistically significant risk factors for longer OS were: age under 55 (5-year OS 57% vs. 8%, p<0.01), CR (37% vs. 0%, p<0.01), CMR (54% vs. 0%, p<0.01), allogeneic transplant (58% vs. 8%, p<0.01) and relapse (67% vs. 0%, p=0.01). In non-transplanted patients with imatinib dose reduction the survival was not inferior compared to patients without a reduction. Surprisingly, these patients were surviving even longer (2-year OS 38% with a reduction vs. 8% without, p<0.01). Whether this finding represents a clinically significant phenomenon or is a mere coincidence remains a question for further investigation.
Conclusion
Adult patients with Ph+ ALL form a distinct subgroup with a very variable prognosis. The best treatment outcome can be reached in younger patients who undergo allogeneic transplant in first haematologic and molecular remission. According to our analysis, imatinib dose reduction due to side effects is not associated with inferior survival. (Supported by Czech Leukemia Study Group – for Life.)
Session topic: E-poster
Keyword(s): Acute lymphoblastic leukemia, Side effects, Therapy, Tyrosine kinase inhibitor
Type: Eposter Presentation
Background
Adult patients with Philadelphia-chromosome positive acute lymphoblastic leukemia (Ph+ ALL) are at high risk of relapse. Allogeneic stem cell transplantation still remains the treatment of choice in spite of the major benefit brought by adding tyrosine kinase inhibitors (TKIs) to the standard chemotherapy. On the other side, TKIs also bear several side effects and some of them require significant dose reductions.
Aims
The aim of this analysis was to focus on treatment strategies in unselected adult Ph+ ALL patients in real clinical practice and how TKI dose reduction may influence their outcomes.
Methods
All adult patients diagnosed with Ph+ ALL and treated with TKIs at our centre between 2005 and 2015 were included into this retrospective analysis. We describe baseline features, treatment options and outcomes. The data were analysed for response and relapse rates and factors affecting survival.
Results
A total number of 41 consecutive patients aged 19 to 82 years (median 58) at the time of diagnosis of Ph+ ALL were included. Leukocyte count was 1.8 to 296 x 109/L (median 20) at presentation. Most commonly observed were common-B immunophenotype (73%) and p190 bcr-abl transcript (63%). Thirteen (32%) patients were treated according to pediatric-based intensive protocol, 13 (32%) using a reduced-toxicity protocol, and 15 (37%) in a palliative approach. An allogeneic transplant was performed in 17 (41%) patients. Thirty-three (85%) patients achieved a complete remission (CR) and 56% of them achieved a complete molecular response (CMR). First line TKI was imatinib in all patients, with a median daily dose of 600mg. In 18 (44%) patients the dose had to be reduced to 400, 300 or 200mg due to side effects (haematological 36%, oedemas 32%, gastrointestinal 16%, skin rash 4%). Sixteen (46%) patients in CR eventually relapsed and only 6 (38%) achieved a second CR. Second line TKI was dasatinib (12; 75%) or 800mg imatinib (3; 19%). Dasatinib was given at a median daily dose of 140mg but in a much broader range (35 to 140 mg). This dose was further decreased in 10 (83%) patients, while most common non-haematological side effects were gastrointestinal (17%), oedemas (13%) and effusion (4%). Five (83%) of these patients in CR2 experienced a second relapse. During the follow-up with a median of 12 months (range 1 to 103 months), 27 (66%) patients died; fifteen (56%) of infection, 11 (41%) of disease progression and one (4 %) of a secondary malignancy. Fourteen (34%) patients are still alive in complete remission. Five-year overall survival (OS) in the whole cohort was 30%. The survival was not influenced by leukocyte count, immunophenotype nor the type of the bcr-abl transcript. The statistically significant risk factors for longer OS were: age under 55 (5-year OS 57% vs. 8%, p<0.01), CR (37% vs. 0%, p<0.01), CMR (54% vs. 0%, p<0.01), allogeneic transplant (58% vs. 8%, p<0.01) and relapse (67% vs. 0%, p=0.01). In non-transplanted patients with imatinib dose reduction the survival was not inferior compared to patients without a reduction. Surprisingly, these patients were surviving even longer (2-year OS 38% with a reduction vs. 8% without, p<0.01). Whether this finding represents a clinically significant phenomenon or is a mere coincidence remains a question for further investigation.
Conclusion
Adult patients with Ph+ ALL form a distinct subgroup with a very variable prognosis. The best treatment outcome can be reached in younger patients who undergo allogeneic transplant in first haematologic and molecular remission. According to our analysis, imatinib dose reduction due to side effects is not associated with inferior survival. (Supported by Czech Leukemia Study Group – for Life.)
Session topic: E-poster
Keyword(s): Acute lymphoblastic leukemia, Side effects, Therapy, Tyrosine kinase inhibitor
Abstract: E876
Type: Eposter Presentation
Background
Adult patients with Philadelphia-chromosome positive acute lymphoblastic leukemia (Ph+ ALL) are at high risk of relapse. Allogeneic stem cell transplantation still remains the treatment of choice in spite of the major benefit brought by adding tyrosine kinase inhibitors (TKIs) to the standard chemotherapy. On the other side, TKIs also bear several side effects and some of them require significant dose reductions.
Aims
The aim of this analysis was to focus on treatment strategies in unselected adult Ph+ ALL patients in real clinical practice and how TKI dose reduction may influence their outcomes.
Methods
All adult patients diagnosed with Ph+ ALL and treated with TKIs at our centre between 2005 and 2015 were included into this retrospective analysis. We describe baseline features, treatment options and outcomes. The data were analysed for response and relapse rates and factors affecting survival.
Results
A total number of 41 consecutive patients aged 19 to 82 years (median 58) at the time of diagnosis of Ph+ ALL were included. Leukocyte count was 1.8 to 296 x 109/L (median 20) at presentation. Most commonly observed were common-B immunophenotype (73%) and p190 bcr-abl transcript (63%). Thirteen (32%) patients were treated according to pediatric-based intensive protocol, 13 (32%) using a reduced-toxicity protocol, and 15 (37%) in a palliative approach. An allogeneic transplant was performed in 17 (41%) patients. Thirty-three (85%) patients achieved a complete remission (CR) and 56% of them achieved a complete molecular response (CMR). First line TKI was imatinib in all patients, with a median daily dose of 600mg. In 18 (44%) patients the dose had to be reduced to 400, 300 or 200mg due to side effects (haematological 36%, oedemas 32%, gastrointestinal 16%, skin rash 4%). Sixteen (46%) patients in CR eventually relapsed and only 6 (38%) achieved a second CR. Second line TKI was dasatinib (12; 75%) or 800mg imatinib (3; 19%). Dasatinib was given at a median daily dose of 140mg but in a much broader range (35 to 140 mg). This dose was further decreased in 10 (83%) patients, while most common non-haematological side effects were gastrointestinal (17%), oedemas (13%) and effusion (4%). Five (83%) of these patients in CR2 experienced a second relapse. During the follow-up with a median of 12 months (range 1 to 103 months), 27 (66%) patients died; fifteen (56%) of infection, 11 (41%) of disease progression and one (4 %) of a secondary malignancy. Fourteen (34%) patients are still alive in complete remission. Five-year overall survival (OS) in the whole cohort was 30%. The survival was not influenced by leukocyte count, immunophenotype nor the type of the bcr-abl transcript. The statistically significant risk factors for longer OS were: age under 55 (5-year OS 57% vs. 8%, p<0.01), CR (37% vs. 0%, p<0.01), CMR (54% vs. 0%, p<0.01), allogeneic transplant (58% vs. 8%, p<0.01) and relapse (67% vs. 0%, p=0.01). In non-transplanted patients with imatinib dose reduction the survival was not inferior compared to patients without a reduction. Surprisingly, these patients were surviving even longer (2-year OS 38% with a reduction vs. 8% without, p<0.01). Whether this finding represents a clinically significant phenomenon or is a mere coincidence remains a question for further investigation.
Conclusion
Adult patients with Ph+ ALL form a distinct subgroup with a very variable prognosis. The best treatment outcome can be reached in younger patients who undergo allogeneic transplant in first haematologic and molecular remission. According to our analysis, imatinib dose reduction due to side effects is not associated with inferior survival. (Supported by Czech Leukemia Study Group – for Life.)
Session topic: E-poster
Keyword(s): Acute lymphoblastic leukemia, Side effects, Therapy, Tyrosine kinase inhibitor
Type: Eposter Presentation
Background
Adult patients with Philadelphia-chromosome positive acute lymphoblastic leukemia (Ph+ ALL) are at high risk of relapse. Allogeneic stem cell transplantation still remains the treatment of choice in spite of the major benefit brought by adding tyrosine kinase inhibitors (TKIs) to the standard chemotherapy. On the other side, TKIs also bear several side effects and some of them require significant dose reductions.
Aims
The aim of this analysis was to focus on treatment strategies in unselected adult Ph+ ALL patients in real clinical practice and how TKI dose reduction may influence their outcomes.
Methods
All adult patients diagnosed with Ph+ ALL and treated with TKIs at our centre between 2005 and 2015 were included into this retrospective analysis. We describe baseline features, treatment options and outcomes. The data were analysed for response and relapse rates and factors affecting survival.
Results
A total number of 41 consecutive patients aged 19 to 82 years (median 58) at the time of diagnosis of Ph+ ALL were included. Leukocyte count was 1.8 to 296 x 109/L (median 20) at presentation. Most commonly observed were common-B immunophenotype (73%) and p190 bcr-abl transcript (63%). Thirteen (32%) patients were treated according to pediatric-based intensive protocol, 13 (32%) using a reduced-toxicity protocol, and 15 (37%) in a palliative approach. An allogeneic transplant was performed in 17 (41%) patients. Thirty-three (85%) patients achieved a complete remission (CR) and 56% of them achieved a complete molecular response (CMR). First line TKI was imatinib in all patients, with a median daily dose of 600mg. In 18 (44%) patients the dose had to be reduced to 400, 300 or 200mg due to side effects (haematological 36%, oedemas 32%, gastrointestinal 16%, skin rash 4%). Sixteen (46%) patients in CR eventually relapsed and only 6 (38%) achieved a second CR. Second line TKI was dasatinib (12; 75%) or 800mg imatinib (3; 19%). Dasatinib was given at a median daily dose of 140mg but in a much broader range (35 to 140 mg). This dose was further decreased in 10 (83%) patients, while most common non-haematological side effects were gastrointestinal (17%), oedemas (13%) and effusion (4%). Five (83%) of these patients in CR2 experienced a second relapse. During the follow-up with a median of 12 months (range 1 to 103 months), 27 (66%) patients died; fifteen (56%) of infection, 11 (41%) of disease progression and one (4 %) of a secondary malignancy. Fourteen (34%) patients are still alive in complete remission. Five-year overall survival (OS) in the whole cohort was 30%. The survival was not influenced by leukocyte count, immunophenotype nor the type of the bcr-abl transcript. The statistically significant risk factors for longer OS were: age under 55 (5-year OS 57% vs. 8%, p<0.01), CR (37% vs. 0%, p<0.01), CMR (54% vs. 0%, p<0.01), allogeneic transplant (58% vs. 8%, p<0.01) and relapse (67% vs. 0%, p=0.01). In non-transplanted patients with imatinib dose reduction the survival was not inferior compared to patients without a reduction. Surprisingly, these patients were surviving even longer (2-year OS 38% with a reduction vs. 8% without, p<0.01). Whether this finding represents a clinically significant phenomenon or is a mere coincidence remains a question for further investigation.
Conclusion
Adult patients with Ph+ ALL form a distinct subgroup with a very variable prognosis. The best treatment outcome can be reached in younger patients who undergo allogeneic transplant in first haematologic and molecular remission. According to our analysis, imatinib dose reduction due to side effects is not associated with inferior survival. (Supported by Czech Leukemia Study Group – for Life.)
Session topic: E-poster
Keyword(s): Acute lymphoblastic leukemia, Side effects, Therapy, Tyrosine kinase inhibitor
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