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On December 11-14, 2021, the 63rd American Society of Hematology (ASH) Annual Meeting will be held as scheduled
.
Professor Jiang Qian's team from Peking University People's Hospital has 5 abstracts selected, including 4 oral and 1 poster, to study and discuss the current problems encountered in the treatment of chronic myeloid leukemia (CML)
.
Yimaitong was fortunate to invite members of Professor Jiang Qian's team to be interviewed, to share interesting facts in the research process, and to interpret the latest research results and their clinical significance
.
FFSPS help select the best treatment strategy TKI Professor Jiang Qian: For CML patients, there are multiple scoring systems can predict the survival of patients, such as Sokal, ELTS and so on
.
At present, CML drugs have a very good effect, and few patients actually die of CML
.
Therefore, we will move the research focus forward, focusing on the factors that can predict the effect of treatment in patients with drug resistance or treatment failure
.
In this regard, we have developed a scoring system to help doctors predict the efficacy of patients' medication before treatment.
For high-risk patients, the risk of treatment failure may be greater, and stronger treatments should be selected accordingly
.
Abstract 632: FFSPS helps choose the best TKI treatment strategy.
CML patients who have not met the 2020 European Leukemia Network (ELN) response criteria through standard dose imatinib treatment should choose to increase the dose or replace the second-generation TKI for treatment Become a clinical problem
.
Professor Jiang Qian’s team developed and verified the FFS Predictive Score (FFSPS) of newly diagnosed CML-CP patients to help doctors choose among these options, and demonstrated it at this year's ASH conference
.
This study found that in the training data set (n=900), WBC≥120×109/L, hemoglobin concentration ≤115 g/L, basophil ≥12% and EUTOS long-term survival (ELTS) risk score were compared with Poor failure-free survival (FFS) is significantly related
.
In the FFSPS scoring system, except for the ELTS high risk score of 2 points, the other scores are all 1 point
.
According to FFSPS, subjects were divided into 5 risk subgroups: extremely low (score = 0), low (score = 1), medium (score = 2), high (score = 3), and extremely high (score ≥ 4)
.
There are significant differences in the 7-year FFS rate of the 5 subgroups, and this is also true in the validation data set
.
In addition, FFSPS is also related to the probability of major molecular response (MMR), MR4.
0 and MR4.
5, progression-free survival (PFS), and survival (all p values <0.
001)
.
FFSPS can predict the probability of successful treatment of patients and help doctors choose the best TKI treatment strategy
.
Orebatinib is safe and effective for CML patients with T315I gene mutation or multi-drug resistance Prof.
Qian Jiang: Orebatinib (olverembatinib), as the third-generation TKI independently developed in China, is resistant to T315I gene mutations or multi-drug resistant CML The patient has a certain curative effect
.
The ASH conference announced phase I and phase II clinical research data.
The efficacy of most patients is stable and persistent, and side effects gradually decrease over time
.
Because CML patients need long-term medication, the long-term effectiveness, safety and stability of the drug are what everyone values and cares about most.
Orebatinib has shown good effectiveness and safety in this study
.
Abstract 311: Phase I study results of a new third-generation TKI oribatinib (HQP1351) in the treatment of TKI-resistant CML patients.
A total of 101 subjects were treated with oribatinib, with a median treatment time of 39 months.
The median follow-up was 30.
8 months
.
The results of the study showed that for TKI-resistant CML-CP or CML-AP patients and long-term treatment patients, oribatinib is effective and well tolerated, with a long-lasting response to treatment, and CML-CP patients with ABL1T315I mutations are more sensitive
.
In the study, there were 11 patients with multiple gene mutations, 1 case achieved complete cytogenetic response (CCyR), 4 cases achieved MMR, and 2 cases achieved MR4.
5
.
Most non-hematological adverse events (AE) were grade 1 or 2
.
Hematological AEs include thrombocytopenia, anemia, leukopenia, etc.
The common SAEs are thrombocytopenia and anemia
.
After 4 years of follow-up, the incidence of AEs decreased significantly
.
Abstract 3598: The latest results of a phase II study of oribatinib in the treatment of TKI-resistant BCR-ABL1T315I mutant CML patients, 32 of 41 CML-CP patients (78%) completed 12 cycles of medication, and most patients reached complete blood Chemical response (CHR), major cytogenetic response (MCyR), CCyR, MMR
.
The PFS rate at 12 months was 89.
3%, and the overall survival (OS) rate was 100%
.
Among 23 CML-AP patients, 14 completed 12 cycles of medication
.
17/23 patients (73.
9%) experienced MaHR, of which 65.
2% CHR and 8.
7% had no evidence of leukemia (NEL); the MCyR rate, CCyR rate, and MMR rate were higher
.
At 12 months, the PFS rate was 74.
1%, and the OS rate was 91.
3%
.
Common hematological AEs in CML-CP patients and CML-AP patients include thrombocytopenia, anemia, leukopenia and neutropenia
.
For non-hematological AEs, skin pigmentation and creatine kinase elevation, ALT and AST elevation are common in CML-CP patients; skin pigmentation and hypocalcemia are common in CML-AP patients
.
The results of the study showed that patients with CML-CP and CML-AP with BCR-ABL1T315I mutations that are resistant to TKI are effective and well tolerated with oribatinib alone
.
Multiple cancer-related gene mutations are related to the poor prognosis of patients receiving the third-generation TKI Professor Qian Jiang: Although the third-generation TKI drugs have shown good safety and effectiveness in the clinical research process, there are still some patients who are The third-generation TKI is tolerable or ineffective
.
We conducted a genomics analysis on which patients can benefit from the third-generation TKI
.
In addition to some clinical variables, cancer-related gene ABL1 mutations or non-ABL1 mutations, mutation types and numbers, as well as high-risk chromosomal karyotypes, high-risk chromosomal abnormalities, number of treatment lines, and responses to previous treatments can be comprehensively estimated The curative effect of the third-generation TKI also explains the reasons why patients are resistant to the third-generation TKI
.
The ELN warning and failure criteria are also applicable to CML-AP patients Professor Jiang Qian: Most of the newly diagnosed CML patients are in the chronic phase, and a small part are in the accelerated phase
.
The accelerated phase does not mean the late stage of the disease, some patients in the accelerated phase are in better condition when they are first diagnosed
.
So we have to distinguish which patients are in poor condition, find out the influencing factors, and develop a scoring system
.
At the same time, we explored whether the second-generation TKI drugs are more effective than imatinib.
After a stratified study, we found that the initial use of the second-generation TKI can quickly obtain a treatment response, but in terms of overall treatment outcome, survival and recurrence There is no obvious benefit in other aspects
.
Abstract 636: Predictive score for the prognosis of patients with CML-AP treated with TKI.
This study identified the relevant factors that affect the efficacy of TKI in patients with CML-AP, and used these factors to develop a prognostic score
.
The results of the study showed that the factors related to the efficacy of CML-AP at the first diagnosis were hemoglobin concentration <100 g/L, platelets <270×109/L, primitive cells>3.
8%, and ≥1 comorbidities
.
According to the number of unfavorable factors, it can be divided into 3 groups: low risk (0), medium risk (1-2), and high risk (3-4)
.
There are significant differences in FFS, PFS and survival rates among different groups
.
The study also shows that using the 2020 ELN standard to issue a warning at 3 months is significantly associated with worse FFS, and failure at 3 months is significantly associated with worse PFS and survival rates, that is, the 2020 ELN chronic phase patient TKI treatment warning and Failure criteria also apply to patients with CML-AP
.
Finally, this study showed through propensity score matching that although patients treated with the second-generation TKI at the initial stage can achieve a treatment response faster, the FFS, PFS and survival rate are similar to those of the patients treated with imatinib at the initial stage, and there is no significant difference.
Benefit
.
Future Prospects Professor Jiang Qian: I think there are three main research directions for CML in the future
.
First, the development of new drugs is still needed in terms of patient resistance
.
The existing three generations of TKI drugs are not safe and effective for every patient
.
Therefore, the research and development of new drugs, especially for patients with relapsed and refractory CML, is still a hot spot, and it will be the same in the future
.
Second, how to minimize drug toxicity as much as possible
.
In the long treatment process, most CML patients cannot stop the drug or the drug withdrawal is unsuccessful, so how can we reduce the drug treatment to the greatest possible alleviation of toxic and side effects, while maintaining the effectiveness of the treatment
.
We are currently studying dose reduction therapy to explore which patients can benefit from dose reduction therapy.
This is the current research focus
.
Third, the identification and management of patients withdrawing medication
.
Some patients with CML have worsened or relapsed after stopping the drug and need to be re-treated with drugs
.
How to identify and manage this type of patients is also an important content of current research
.
Professor Jiang Qian, Doctor of Medicine, Chief Physician, Professor, PhD Supervisor, Deputy Director, Department of Hematology, Peking University People’s Hospital, Member of the National Representative Committee of the International CML Foundation, Member of the Hematology Branch of the Chinese Medical Association, and Deputy Leader of the Leukemia Lymphoma Group, Beijing Medical Association Blood Chairman-designate of the Academic Division, Chairman of the Leukemia Branch of the Chinese Medical Education Association, Vice Chairman of the Hematology Branch of the Chinese Medical Education Association, Leukemia Research, Chinese Journal of Hematology, Chinese Journal of Experimental Hematology, and Editorial Board of the Journal of Clinical Hematology References: [1] ASH 2021,abstract#632.
[2]ASH 2021,abstract#311.
[3]ASH 2021,abstract#3598.
[4]ASH 2021,abstract#308.
[5]ASH 2021,abstract#636.
Stamp" to read Original ", we make progress together
.
Professor Jiang Qian's team from Peking University People's Hospital has 5 abstracts selected, including 4 oral and 1 poster, to study and discuss the current problems encountered in the treatment of chronic myeloid leukemia (CML)
.
Yimaitong was fortunate to invite members of Professor Jiang Qian's team to be interviewed, to share interesting facts in the research process, and to interpret the latest research results and their clinical significance
.
FFSPS help select the best treatment strategy TKI Professor Jiang Qian: For CML patients, there are multiple scoring systems can predict the survival of patients, such as Sokal, ELTS and so on
.
At present, CML drugs have a very good effect, and few patients actually die of CML
.
Therefore, we will move the research focus forward, focusing on the factors that can predict the effect of treatment in patients with drug resistance or treatment failure
.
In this regard, we have developed a scoring system to help doctors predict the efficacy of patients' medication before treatment.
For high-risk patients, the risk of treatment failure may be greater, and stronger treatments should be selected accordingly
.
Abstract 632: FFSPS helps choose the best TKI treatment strategy.
CML patients who have not met the 2020 European Leukemia Network (ELN) response criteria through standard dose imatinib treatment should choose to increase the dose or replace the second-generation TKI for treatment Become a clinical problem
.
Professor Jiang Qian’s team developed and verified the FFS Predictive Score (FFSPS) of newly diagnosed CML-CP patients to help doctors choose among these options, and demonstrated it at this year's ASH conference
.
This study found that in the training data set (n=900), WBC≥120×109/L, hemoglobin concentration ≤115 g/L, basophil ≥12% and EUTOS long-term survival (ELTS) risk score were compared with Poor failure-free survival (FFS) is significantly related
.
In the FFSPS scoring system, except for the ELTS high risk score of 2 points, the other scores are all 1 point
.
According to FFSPS, subjects were divided into 5 risk subgroups: extremely low (score = 0), low (score = 1), medium (score = 2), high (score = 3), and extremely high (score ≥ 4)
.
There are significant differences in the 7-year FFS rate of the 5 subgroups, and this is also true in the validation data set
.
In addition, FFSPS is also related to the probability of major molecular response (MMR), MR4.
0 and MR4.
5, progression-free survival (PFS), and survival (all p values <0.
001)
.
FFSPS can predict the probability of successful treatment of patients and help doctors choose the best TKI treatment strategy
.
Orebatinib is safe and effective for CML patients with T315I gene mutation or multi-drug resistance Prof.
Qian Jiang: Orebatinib (olverembatinib), as the third-generation TKI independently developed in China, is resistant to T315I gene mutations or multi-drug resistant CML The patient has a certain curative effect
.
The ASH conference announced phase I and phase II clinical research data.
The efficacy of most patients is stable and persistent, and side effects gradually decrease over time
.
Because CML patients need long-term medication, the long-term effectiveness, safety and stability of the drug are what everyone values and cares about most.
Orebatinib has shown good effectiveness and safety in this study
.
Abstract 311: Phase I study results of a new third-generation TKI oribatinib (HQP1351) in the treatment of TKI-resistant CML patients.
A total of 101 subjects were treated with oribatinib, with a median treatment time of 39 months.
The median follow-up was 30.
8 months
.
The results of the study showed that for TKI-resistant CML-CP or CML-AP patients and long-term treatment patients, oribatinib is effective and well tolerated, with a long-lasting response to treatment, and CML-CP patients with ABL1T315I mutations are more sensitive
.
In the study, there were 11 patients with multiple gene mutations, 1 case achieved complete cytogenetic response (CCyR), 4 cases achieved MMR, and 2 cases achieved MR4.
5
.
Most non-hematological adverse events (AE) were grade 1 or 2
.
Hematological AEs include thrombocytopenia, anemia, leukopenia, etc.
The common SAEs are thrombocytopenia and anemia
.
After 4 years of follow-up, the incidence of AEs decreased significantly
.
Abstract 3598: The latest results of a phase II study of oribatinib in the treatment of TKI-resistant BCR-ABL1T315I mutant CML patients, 32 of 41 CML-CP patients (78%) completed 12 cycles of medication, and most patients reached complete blood Chemical response (CHR), major cytogenetic response (MCyR), CCyR, MMR
.
The PFS rate at 12 months was 89.
3%, and the overall survival (OS) rate was 100%
.
Among 23 CML-AP patients, 14 completed 12 cycles of medication
.
17/23 patients (73.
9%) experienced MaHR, of which 65.
2% CHR and 8.
7% had no evidence of leukemia (NEL); the MCyR rate, CCyR rate, and MMR rate were higher
.
At 12 months, the PFS rate was 74.
1%, and the OS rate was 91.
3%
.
Common hematological AEs in CML-CP patients and CML-AP patients include thrombocytopenia, anemia, leukopenia and neutropenia
.
For non-hematological AEs, skin pigmentation and creatine kinase elevation, ALT and AST elevation are common in CML-CP patients; skin pigmentation and hypocalcemia are common in CML-AP patients
.
The results of the study showed that patients with CML-CP and CML-AP with BCR-ABL1T315I mutations that are resistant to TKI are effective and well tolerated with oribatinib alone
.
Multiple cancer-related gene mutations are related to the poor prognosis of patients receiving the third-generation TKI Professor Qian Jiang: Although the third-generation TKI drugs have shown good safety and effectiveness in the clinical research process, there are still some patients who are The third-generation TKI is tolerable or ineffective
.
We conducted a genomics analysis on which patients can benefit from the third-generation TKI
.
In addition to some clinical variables, cancer-related gene ABL1 mutations or non-ABL1 mutations, mutation types and numbers, as well as high-risk chromosomal karyotypes, high-risk chromosomal abnormalities, number of treatment lines, and responses to previous treatments can be comprehensively estimated The curative effect of the third-generation TKI also explains the reasons why patients are resistant to the third-generation TKI
.
The ELN warning and failure criteria are also applicable to CML-AP patients Professor Jiang Qian: Most of the newly diagnosed CML patients are in the chronic phase, and a small part are in the accelerated phase
.
The accelerated phase does not mean the late stage of the disease, some patients in the accelerated phase are in better condition when they are first diagnosed
.
So we have to distinguish which patients are in poor condition, find out the influencing factors, and develop a scoring system
.
At the same time, we explored whether the second-generation TKI drugs are more effective than imatinib.
After a stratified study, we found that the initial use of the second-generation TKI can quickly obtain a treatment response, but in terms of overall treatment outcome, survival and recurrence There is no obvious benefit in other aspects
.
Abstract 636: Predictive score for the prognosis of patients with CML-AP treated with TKI.
This study identified the relevant factors that affect the efficacy of TKI in patients with CML-AP, and used these factors to develop a prognostic score
.
The results of the study showed that the factors related to the efficacy of CML-AP at the first diagnosis were hemoglobin concentration <100 g/L, platelets <270×109/L, primitive cells>3.
8%, and ≥1 comorbidities
.
According to the number of unfavorable factors, it can be divided into 3 groups: low risk (0), medium risk (1-2), and high risk (3-4)
.
There are significant differences in FFS, PFS and survival rates among different groups
.
The study also shows that using the 2020 ELN standard to issue a warning at 3 months is significantly associated with worse FFS, and failure at 3 months is significantly associated with worse PFS and survival rates, that is, the 2020 ELN chronic phase patient TKI treatment warning and Failure criteria also apply to patients with CML-AP
.
Finally, this study showed through propensity score matching that although patients treated with the second-generation TKI at the initial stage can achieve a treatment response faster, the FFS, PFS and survival rate are similar to those of the patients treated with imatinib at the initial stage, and there is no significant difference.
Benefit
.
Future Prospects Professor Jiang Qian: I think there are three main research directions for CML in the future
.
First, the development of new drugs is still needed in terms of patient resistance
.
The existing three generations of TKI drugs are not safe and effective for every patient
.
Therefore, the research and development of new drugs, especially for patients with relapsed and refractory CML, is still a hot spot, and it will be the same in the future
.
Second, how to minimize drug toxicity as much as possible
.
In the long treatment process, most CML patients cannot stop the drug or the drug withdrawal is unsuccessful, so how can we reduce the drug treatment to the greatest possible alleviation of toxic and side effects, while maintaining the effectiveness of the treatment
.
We are currently studying dose reduction therapy to explore which patients can benefit from dose reduction therapy.
This is the current research focus
.
Third, the identification and management of patients withdrawing medication
.
Some patients with CML have worsened or relapsed after stopping the drug and need to be re-treated with drugs
.
How to identify and manage this type of patients is also an important content of current research
.
Professor Jiang Qian, Doctor of Medicine, Chief Physician, Professor, PhD Supervisor, Deputy Director, Department of Hematology, Peking University People’s Hospital, Member of the National Representative Committee of the International CML Foundation, Member of the Hematology Branch of the Chinese Medical Association, and Deputy Leader of the Leukemia Lymphoma Group, Beijing Medical Association Blood Chairman-designate of the Academic Division, Chairman of the Leukemia Branch of the Chinese Medical Education Association, Vice Chairman of the Hematology Branch of the Chinese Medical Education Association, Leukemia Research, Chinese Journal of Hematology, Chinese Journal of Experimental Hematology, and Editorial Board of the Journal of Clinical Hematology References: [1] ASH 2021,abstract#632.
[2]ASH 2021,abstract#311.
[3]ASH 2021,abstract#3598.
[4]ASH 2021,abstract#308.
[5]ASH 2021,abstract#636.
Stamp" to read Original ", we make progress together
