Contributions
Abstract: PB1911
Type: Publication Only
Background
The BCR-ABL1 tyrosine kinase inhibitors (TKIs) became standard therapy for chronic phase (CP) chronic myeloid leukemia (CML) since imatinib mesylate (IM) was approved as frontline therapy. Complete cytogenetic response (CCyR) has been established as a predictor for disease outcome by the International Randomized Study of Interferon and STI571 (IRIS), and based on many clinical studies. The National Comprehensive Cancer Network (NCCN) and the European Leukemia Net (ELN) have established treatment guidelines that include molecular response milestones. Although failure to achieve these milestones means that switching to a different TKI is needed to limit the risk of progression and death, there is insufficient data to show long-term outcomes in the patients who were in a molecular failure after 24 months (CCyR but not MMR).
Aims
The aim of this study was to evaluate long-term survival end points and identify predictive factors for an achievement of overall major molecular response (MMR) in the patients who have achieved CCyR but not MMR after 24 months on frontline IM therapy, as additional information to guide clinical decisions on selecting patients.
Methods
Among 604 newly diagnosed CP CML patients who received IM for at least 2 years with no prior treatment, 288 (47.7%) patients achieved CCyR but not MMR after 24 months on frontline IM therapy. Finally, to evaluate molecular responses, 280 patients with transcript type of b2a2 and b3a2 were included in this analysis. All qRT-PCR were tested with at least 4.5-log sensitivity in a single laboratory (Leukemia Research Institute, The Catholic University of Korea, Seoul, Korea).
Results
280 newly diagnosed CP CML patients (including 190 men and 90 women) were evaluated. With a median age of 38.1 years (range, 5-77 years), the distribution of low, intermediate, and high Sokal risk scores were 22%, 35% and 43%, respectively, excluding 30 patients with unknown risk. With a median follow-up of 134.2 months (range, 25.6–195.0 months), 163(58%) patients continued IM and maintained at least a complete cytogenetic response (CCyR), while 117 patients permanently discontinued IM due to intolerance (n = 31), warnings according to ELN 2013 recommendations with adverse events (n = 43), and treatment failure (n = 17), progression (n = 9), death (n = 1), enrollment of treatment-free remission (TFR) study (n = 10), and others (n = 6).
Among them, 98 (84%) switched to second-generation tyrosine kinase inhibitors (2G TKIs). The CI rates of MMR by 3, 4, and 5 years were 27.9 ± 2.8%, 53.6 ± 3.3%, and 71.8 ± 3.0%, respectively, and the CI rates of CMR by 3, 4, and 5 years were 1.9 ± 0.8%, 5.0 ± 1.4%, and 10.8 ± 2.1%, respectively. The 10-year FFS, PFS, and OS were 89.3 ± 2.2%, 96.0 ± 1.3%, and 98.5 ± 0.9%, respectively. The patients with transcript type of b3a2, compared to b2a2 (RR of 0.22, P = 0.001) and high Sokal risk, compared to low Sokal risk (RR of 0.67, P = 0.040) showed a lower rate of overall MMR achievement on IM therapy.
Conclusion
This study demonstrated long-term survival outcomes in the patients who have achieved CCyR but not MMR after 24 months on frontline IM therapy. In addition, we identify the factors related to an achievement of overall MMR. It provides additional information to guide clinical decisions on selecting high-risk patients. Based on our findings, clinical investigations considering what the treatment goals are, overall survival with a low risk of toxicity or achieving of a deeper molecular response with a hope for TFR, are needed.
Session topic: 8. Chronic myeloid leukemia - Clinical
Keyword(s): Chronic myeloid leukemia, imatinib, Molecular response
Abstract: PB1911
Type: Publication Only
Background
The BCR-ABL1 tyrosine kinase inhibitors (TKIs) became standard therapy for chronic phase (CP) chronic myeloid leukemia (CML) since imatinib mesylate (IM) was approved as frontline therapy. Complete cytogenetic response (CCyR) has been established as a predictor for disease outcome by the International Randomized Study of Interferon and STI571 (IRIS), and based on many clinical studies. The National Comprehensive Cancer Network (NCCN) and the European Leukemia Net (ELN) have established treatment guidelines that include molecular response milestones. Although failure to achieve these milestones means that switching to a different TKI is needed to limit the risk of progression and death, there is insufficient data to show long-term outcomes in the patients who were in a molecular failure after 24 months (CCyR but not MMR).
Aims
The aim of this study was to evaluate long-term survival end points and identify predictive factors for an achievement of overall major molecular response (MMR) in the patients who have achieved CCyR but not MMR after 24 months on frontline IM therapy, as additional information to guide clinical decisions on selecting patients.
Methods
Among 604 newly diagnosed CP CML patients who received IM for at least 2 years with no prior treatment, 288 (47.7%) patients achieved CCyR but not MMR after 24 months on frontline IM therapy. Finally, to evaluate molecular responses, 280 patients with transcript type of b2a2 and b3a2 were included in this analysis. All qRT-PCR were tested with at least 4.5-log sensitivity in a single laboratory (Leukemia Research Institute, The Catholic University of Korea, Seoul, Korea).
Results
280 newly diagnosed CP CML patients (including 190 men and 90 women) were evaluated. With a median age of 38.1 years (range, 5-77 years), the distribution of low, intermediate, and high Sokal risk scores were 22%, 35% and 43%, respectively, excluding 30 patients with unknown risk. With a median follow-up of 134.2 months (range, 25.6–195.0 months), 163(58%) patients continued IM and maintained at least a complete cytogenetic response (CCyR), while 117 patients permanently discontinued IM due to intolerance (n = 31), warnings according to ELN 2013 recommendations with adverse events (n = 43), and treatment failure (n = 17), progression (n = 9), death (n = 1), enrollment of treatment-free remission (TFR) study (n = 10), and others (n = 6).
Among them, 98 (84%) switched to second-generation tyrosine kinase inhibitors (2G TKIs). The CI rates of MMR by 3, 4, and 5 years were 27.9 ± 2.8%, 53.6 ± 3.3%, and 71.8 ± 3.0%, respectively, and the CI rates of CMR by 3, 4, and 5 years were 1.9 ± 0.8%, 5.0 ± 1.4%, and 10.8 ± 2.1%, respectively. The 10-year FFS, PFS, and OS were 89.3 ± 2.2%, 96.0 ± 1.3%, and 98.5 ± 0.9%, respectively. The patients with transcript type of b3a2, compared to b2a2 (RR of 0.22, P = 0.001) and high Sokal risk, compared to low Sokal risk (RR of 0.67, P = 0.040) showed a lower rate of overall MMR achievement on IM therapy.
Conclusion
This study demonstrated long-term survival outcomes in the patients who have achieved CCyR but not MMR after 24 months on frontline IM therapy. In addition, we identify the factors related to an achievement of overall MMR. It provides additional information to guide clinical decisions on selecting high-risk patients. Based on our findings, clinical investigations considering what the treatment goals are, overall survival with a low risk of toxicity or achieving of a deeper molecular response with a hope for TFR, are needed.
Session topic: 8. Chronic myeloid leukemia - Clinical
Keyword(s): Chronic myeloid leukemia, imatinib, Molecular response