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Dr. Pinilla-Ibarz scans the journals, so you don’t have to!

Javier Pinilla-Ibarz, MD, PhD 
Treatment free remission (TFR) is now a standard of care in patients with chronic phase CML who have achieved a deep molecular response long enough to allow discontinuation. While most of the data available are based on past well controlled clinical trials, there is not much data about real-world discontinuation outside clinical trials. Recently Flygt et al reported the outcomes of a large population of CML patients from the Swedish CML registry and assessed TKI discontinuation outside a clinical trial. Out of 584 evaluable patients with a median follow up of nine years from diagnosis, 128 (23%) discontinued TKI therapy (≥1 month) due to achieving a DMR (deep molecular response) From this group, 49% re‐initiated TKI treatment (median time to restart 4·8 months). In all, 38 patients stopped TKI within a clinical study and 90 outside a study. After 24 months 41·1% of patients discontinuing outside a study had re‐initiated TKI treatment. As previously described, TKI treatment duration pre‐stop was longer and proportion treated with second‐generation TKI slightly higher outside studies, conceivably affecting the clinical outcome. Once again, these data support the possibility of TKI discontinuation in appropriate patients following current guidelines and close follow up after.

 


One of the most important goals in the treatment of patients with CP-CML is to avoid the progression to advanced phases, such as accelerated and blast phase, where the treatments are limited and the outcomes inferior. The long term outcomes of patients with lymphoid blast crisis treated with HyperCVAD plus dasatinib was recently reported by Morita et al. The authors reviewed 85 patients (23 with CML- LBP and 62 with newly diagnosed Ph- positive ALL) who received hyper- CVAD plus dasatinib. In the CML- LBP cohort, 19 had prior chronic myeloid leukemia as chronic phase (n = 17; 74%), accelerated phase (n = 1; 4%), or myeloid blastic phase (n = 1; 4%); 4 (17%) presented with de novo CML- LBP. Patients with CML- LBP were less likely to achieve deep molecular remission than patients with Ph- positive ALL. The major molecular response (MMR) rates were 70% and 95%, respectively (P = .007), and the complete molecular response (CMR) rates were 55% and 74%, respectively (P = .16). However, the survival outcomes were similar for CML- LBP and Ph- positive ALL: The 5- year overall survival (OS) rates were 59% and 48%, respectively (P = .97). Allogeneic stem cell transplantation was associated with a better outcome in CML- LBP (5- year OS rate, 88% vs 57%; P = .04), while in Ph- positive ALL, the outcome was driven by deeper molecular remission: the 5- year OS rates were 63% and 25% with CMR and MMR, respectively (P = .002). Although the outcome of CML- LBP has improved with hyper- CVAD plus dasatinib therapy with survival comparable to that of Ph- positive ALL, data with third generation TKI may even improve these outcomes in the near future.

 

Allogeneic BMT is the ultimate therapy for resistant or intolerant to TKI patients with CP-CML as well as for advances phases of this disease. Since the introduction of TKI the rates of allo BMT had overall decreased, so Yassine and colleagues performed a systematic review/meta-analysis of the available literature to assess the evidence regarding allo-HCT efficacy in CP-CML patients. Data from eligible studies were extracted in relation to benefits (overall survival [OS], progression-free survival, disease-free survival [DFS], complete remission [CR], and molecular response [MR]) and harms (nonrelapse mortality [NRM], relapse, and acute and chronic graft-versus-host disease) and stratified by age into adult and pediatric groups. Overall for adult allo-HCT recipients, the pooled OS, DFS, CR and, MR were 84%, 66%, 56%, and 88%, respectively. Pooled NRM and relapse were 20% and 19%, respectively. As a conclusion, these results suggest that allo-HCT still is an effective treatment for TKI-resistant or TKI-intolerant CP-CML and the risk-befit ratio is favorable based on the lack of other alternatives.

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Javier Pinilla-Ibarz MD, PhD, Senior Member, Lymphoma Section Head and Director of Immunotherapy, Malignant Hematology Department, H.Lee Moffitt Cancer Center & Research Institute

Javier Pinilla has disclosed the following relevant financial relationships:

Serve(d) as a speaker or a member of a speakers bureau for: Abbvie; Janssen; Takeda; AstraZeneca
Received research grant from: TG therapeutics; MEI; Sunesis
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Javier Pinilla-Ibarz MD, PhD, Senior Member, Lymphoma Section Head and Director of Immunotherapy, Malignant Hematology Department, H.Lee Moffitt Cancer Center & Research Institute

Javier Pinilla has disclosed the following relevant financial relationships:

Serve(d) as a speaker or a member of a speakers bureau for: Abbvie; Janssen; Takeda; AstraZeneca
Received research grant from: TG therapeutics; MEI; Sunesis
Author and Disclosure Information

Javier Pinilla-Ibarz MD, PhD, Senior Member, Lymphoma Section Head and Director of Immunotherapy, Malignant Hematology Department, H.Lee Moffitt Cancer Center & Research Institute

Javier Pinilla has disclosed the following relevant financial relationships:

Serve(d) as a speaker or a member of a speakers bureau for: Abbvie; Janssen; Takeda; AstraZeneca
Received research grant from: TG therapeutics; MEI; Sunesis
Dr. Pinilla-Ibarz scans the journals, so you don’t have to!
Dr. Pinilla-Ibarz scans the journals, so you don’t have to!

Javier Pinilla-Ibarz, MD, PhD 
Treatment free remission (TFR) is now a standard of care in patients with chronic phase CML who have achieved a deep molecular response long enough to allow discontinuation. While most of the data available are based on past well controlled clinical trials, there is not much data about real-world discontinuation outside clinical trials. Recently Flygt et al reported the outcomes of a large population of CML patients from the Swedish CML registry and assessed TKI discontinuation outside a clinical trial. Out of 584 evaluable patients with a median follow up of nine years from diagnosis, 128 (23%) discontinued TKI therapy (≥1 month) due to achieving a DMR (deep molecular response) From this group, 49% re‐initiated TKI treatment (median time to restart 4·8 months). In all, 38 patients stopped TKI within a clinical study and 90 outside a study. After 24 months 41·1% of patients discontinuing outside a study had re‐initiated TKI treatment. As previously described, TKI treatment duration pre‐stop was longer and proportion treated with second‐generation TKI slightly higher outside studies, conceivably affecting the clinical outcome. Once again, these data support the possibility of TKI discontinuation in appropriate patients following current guidelines and close follow up after.

 


One of the most important goals in the treatment of patients with CP-CML is to avoid the progression to advanced phases, such as accelerated and blast phase, where the treatments are limited and the outcomes inferior. The long term outcomes of patients with lymphoid blast crisis treated with HyperCVAD plus dasatinib was recently reported by Morita et al. The authors reviewed 85 patients (23 with CML- LBP and 62 with newly diagnosed Ph- positive ALL) who received hyper- CVAD plus dasatinib. In the CML- LBP cohort, 19 had prior chronic myeloid leukemia as chronic phase (n = 17; 74%), accelerated phase (n = 1; 4%), or myeloid blastic phase (n = 1; 4%); 4 (17%) presented with de novo CML- LBP. Patients with CML- LBP were less likely to achieve deep molecular remission than patients with Ph- positive ALL. The major molecular response (MMR) rates were 70% and 95%, respectively (P = .007), and the complete molecular response (CMR) rates were 55% and 74%, respectively (P = .16). However, the survival outcomes were similar for CML- LBP and Ph- positive ALL: The 5- year overall survival (OS) rates were 59% and 48%, respectively (P = .97). Allogeneic stem cell transplantation was associated with a better outcome in CML- LBP (5- year OS rate, 88% vs 57%; P = .04), while in Ph- positive ALL, the outcome was driven by deeper molecular remission: the 5- year OS rates were 63% and 25% with CMR and MMR, respectively (P = .002). Although the outcome of CML- LBP has improved with hyper- CVAD plus dasatinib therapy with survival comparable to that of Ph- positive ALL, data with third generation TKI may even improve these outcomes in the near future.

 

Allogeneic BMT is the ultimate therapy for resistant or intolerant to TKI patients with CP-CML as well as for advances phases of this disease. Since the introduction of TKI the rates of allo BMT had overall decreased, so Yassine and colleagues performed a systematic review/meta-analysis of the available literature to assess the evidence regarding allo-HCT efficacy in CP-CML patients. Data from eligible studies were extracted in relation to benefits (overall survival [OS], progression-free survival, disease-free survival [DFS], complete remission [CR], and molecular response [MR]) and harms (nonrelapse mortality [NRM], relapse, and acute and chronic graft-versus-host disease) and stratified by age into adult and pediatric groups. Overall for adult allo-HCT recipients, the pooled OS, DFS, CR and, MR were 84%, 66%, 56%, and 88%, respectively. Pooled NRM and relapse were 20% and 19%, respectively. As a conclusion, these results suggest that allo-HCT still is an effective treatment for TKI-resistant or TKI-intolerant CP-CML and the risk-befit ratio is favorable based on the lack of other alternatives.

Javier Pinilla-Ibarz, MD, PhD 
Treatment free remission (TFR) is now a standard of care in patients with chronic phase CML who have achieved a deep molecular response long enough to allow discontinuation. While most of the data available are based on past well controlled clinical trials, there is not much data about real-world discontinuation outside clinical trials. Recently Flygt et al reported the outcomes of a large population of CML patients from the Swedish CML registry and assessed TKI discontinuation outside a clinical trial. Out of 584 evaluable patients with a median follow up of nine years from diagnosis, 128 (23%) discontinued TKI therapy (≥1 month) due to achieving a DMR (deep molecular response) From this group, 49% re‐initiated TKI treatment (median time to restart 4·8 months). In all, 38 patients stopped TKI within a clinical study and 90 outside a study. After 24 months 41·1% of patients discontinuing outside a study had re‐initiated TKI treatment. As previously described, TKI treatment duration pre‐stop was longer and proportion treated with second‐generation TKI slightly higher outside studies, conceivably affecting the clinical outcome. Once again, these data support the possibility of TKI discontinuation in appropriate patients following current guidelines and close follow up after.

 


One of the most important goals in the treatment of patients with CP-CML is to avoid the progression to advanced phases, such as accelerated and blast phase, where the treatments are limited and the outcomes inferior. The long term outcomes of patients with lymphoid blast crisis treated with HyperCVAD plus dasatinib was recently reported by Morita et al. The authors reviewed 85 patients (23 with CML- LBP and 62 with newly diagnosed Ph- positive ALL) who received hyper- CVAD plus dasatinib. In the CML- LBP cohort, 19 had prior chronic myeloid leukemia as chronic phase (n = 17; 74%), accelerated phase (n = 1; 4%), or myeloid blastic phase (n = 1; 4%); 4 (17%) presented with de novo CML- LBP. Patients with CML- LBP were less likely to achieve deep molecular remission than patients with Ph- positive ALL. The major molecular response (MMR) rates were 70% and 95%, respectively (P = .007), and the complete molecular response (CMR) rates were 55% and 74%, respectively (P = .16). However, the survival outcomes were similar for CML- LBP and Ph- positive ALL: The 5- year overall survival (OS) rates were 59% and 48%, respectively (P = .97). Allogeneic stem cell transplantation was associated with a better outcome in CML- LBP (5- year OS rate, 88% vs 57%; P = .04), while in Ph- positive ALL, the outcome was driven by deeper molecular remission: the 5- year OS rates were 63% and 25% with CMR and MMR, respectively (P = .002). Although the outcome of CML- LBP has improved with hyper- CVAD plus dasatinib therapy with survival comparable to that of Ph- positive ALL, data with third generation TKI may even improve these outcomes in the near future.

 

Allogeneic BMT is the ultimate therapy for resistant or intolerant to TKI patients with CP-CML as well as for advances phases of this disease. Since the introduction of TKI the rates of allo BMT had overall decreased, so Yassine and colleagues performed a systematic review/meta-analysis of the available literature to assess the evidence regarding allo-HCT efficacy in CP-CML patients. Data from eligible studies were extracted in relation to benefits (overall survival [OS], progression-free survival, disease-free survival [DFS], complete remission [CR], and molecular response [MR]) and harms (nonrelapse mortality [NRM], relapse, and acute and chronic graft-versus-host disease) and stratified by age into adult and pediatric groups. Overall for adult allo-HCT recipients, the pooled OS, DFS, CR and, MR were 84%, 66%, 56%, and 88%, respectively. Pooled NRM and relapse were 20% and 19%, respectively. As a conclusion, these results suggest that allo-HCT still is an effective treatment for TKI-resistant or TKI-intolerant CP-CML and the risk-befit ratio is favorable based on the lack of other alternatives.

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