Contributions
Abstract: PB1941
Type: Publication Only
Background
The extreme effectiveness of tyrosine kinase inhibitors (TKI) has dramatically changed the clinical course and outcome of chronic myeloid leukemia (CML) patients (pts). Generally, the achievement of optimal molecular response (MR) predicts close to normal survival. In contrast, pts who fail to respond to TKI have an inferior prognosis. Whether long-term survival is possible in pts resistant to all used TKIs, and if the absence of MR is inevitably associated with a fatal outcome is not well determined.
Aims
To determine the proportion of CML pts treated with TKIs without any molecular response among more than 10-years survivors.
Methods
We retrieved 340 CML pts (168 females and 172 males; mean age of 521±16.4 years), who were diagnosed between 1998 and 2008, with a follow-up of at least 10 years after the diagnosis in the hospital records of the National Specialized Hospital for Active Treatment of Hematological Diseases – Sofia, Bulgaria. Pts were treated with chemotherapy, interferon alpha and/or by TKI. Response to therapy was evaluated according to the standard criteria. Molecular monitoring was carried-out initially by nested primers RT-PCR, afterwards by manual quantitative RT-PCR, and since 2012 by GenExpert (Cepheid) platform.
Results
In total 88/340 pts had ≥10-years survival, including 24 who achieved MR5.0 (27.3%); 13 MR4.5 (14.8%); 8 MR4 (9.1%); 19 MR3.0 (21.6%). No MR was found in the remaining 24 pts (27.3%). All refractory pts received at least 3 different TKIs with or without preceding chemotherapy or interferon alpha. All pts expressed typical BCR-ABL1 mRNAs (13 with b3a2; 11 with b2a2), and all were diagnosed in chronic phase except one who presented in accelerated phase. The mean leukocyte count was 153.9±82.7x109/l; platelet count 629.9±405.8x109/l; and hemoglobin 125.5±30.1 g/l. All pts with available records were EUTOS score low risk. No significant differences in the main clinical and laboratory features between pts with or without MR were seen. All 24 pts achieved complete hematological response without any MR, with only a transient 1 log reduction of the BCR-ABL1 level after the 2nd line TKI initiation in 2 of them. T315I ABL1 mutation was found in only 1/24 (4.2%) case. During the whole period of observation, 6 (27.3%) nonresponders developed ≥1 blast crisis, while none of the pts with an achieved MR progressed. In terms of survival, 8 of the non-responders died 10-18 years after diagnosis. The remaining 16 are still alive 10-19 years after the onset.
Conclusion
Our results suggest that long-term survival might be observed in some low risk CML pts who achieved hematological response, in the absence of any molecular response to several lines of TKIs. A possible role of variations in the biology of the disease and/or a certain sensitizing effect of the preceding therapy at least in some of the pts can be speculated. Additional studies are warranted to elucidate the mechanisms underlying this observation as well as to search for additional indicators for prediction of outcomes.
Acknowledgements: The present study was supported by the National Science Fund, Ministry of Education and Science.
Session topic: 8. Chronic myeloid leukemia - Clinical
Keyword(s): Chronic myeloid leukemia, Long-term follow-up, Molecular response
Abstract: PB1941
Type: Publication Only
Background
The extreme effectiveness of tyrosine kinase inhibitors (TKI) has dramatically changed the clinical course and outcome of chronic myeloid leukemia (CML) patients (pts). Generally, the achievement of optimal molecular response (MR) predicts close to normal survival. In contrast, pts who fail to respond to TKI have an inferior prognosis. Whether long-term survival is possible in pts resistant to all used TKIs, and if the absence of MR is inevitably associated with a fatal outcome is not well determined.
Aims
To determine the proportion of CML pts treated with TKIs without any molecular response among more than 10-years survivors.
Methods
We retrieved 340 CML pts (168 females and 172 males; mean age of 521±16.4 years), who were diagnosed between 1998 and 2008, with a follow-up of at least 10 years after the diagnosis in the hospital records of the National Specialized Hospital for Active Treatment of Hematological Diseases – Sofia, Bulgaria. Pts were treated with chemotherapy, interferon alpha and/or by TKI. Response to therapy was evaluated according to the standard criteria. Molecular monitoring was carried-out initially by nested primers RT-PCR, afterwards by manual quantitative RT-PCR, and since 2012 by GenExpert (Cepheid) platform.
Results
In total 88/340 pts had ≥10-years survival, including 24 who achieved MR5.0 (27.3%); 13 MR4.5 (14.8%); 8 MR4 (9.1%); 19 MR3.0 (21.6%). No MR was found in the remaining 24 pts (27.3%). All refractory pts received at least 3 different TKIs with or without preceding chemotherapy or interferon alpha. All pts expressed typical BCR-ABL1 mRNAs (13 with b3a2; 11 with b2a2), and all were diagnosed in chronic phase except one who presented in accelerated phase. The mean leukocyte count was 153.9±82.7x109/l; platelet count 629.9±405.8x109/l; and hemoglobin 125.5±30.1 g/l. All pts with available records were EUTOS score low risk. No significant differences in the main clinical and laboratory features between pts with or without MR were seen. All 24 pts achieved complete hematological response without any MR, with only a transient 1 log reduction of the BCR-ABL1 level after the 2nd line TKI initiation in 2 of them. T315I ABL1 mutation was found in only 1/24 (4.2%) case. During the whole period of observation, 6 (27.3%) nonresponders developed ≥1 blast crisis, while none of the pts with an achieved MR progressed. In terms of survival, 8 of the non-responders died 10-18 years after diagnosis. The remaining 16 are still alive 10-19 years after the onset.
Conclusion
Our results suggest that long-term survival might be observed in some low risk CML pts who achieved hematological response, in the absence of any molecular response to several lines of TKIs. A possible role of variations in the biology of the disease and/or a certain sensitizing effect of the preceding therapy at least in some of the pts can be speculated. Additional studies are warranted to elucidate the mechanisms underlying this observation as well as to search for additional indicators for prediction of outcomes.
Acknowledgements: The present study was supported by the National Science Fund, Ministry of Education and Science.
Session topic: 8. Chronic myeloid leukemia - Clinical
Keyword(s): Chronic myeloid leukemia, Long-term follow-up, Molecular response