Key clinical point: Patients with chronic-phase chronic myeloid leukemia (CML-CP) receiving a second-generation tyrosine kinase inhibitor (TKI) frontline and fulfilling eligibility criteria for European LeukemiaNet 2020 treatment-free remission (TFR) recommendations had the highest molecular recurrence-free survival (MRFS) after TKI discontinuation.

Major finding: MRFS at 2 and 5 years were 51.8% and 43.8%, respectively. MRFS was significantly higher in patients who fulfilled TFR recommendations vs. those who did not (P = .005). Molecular recurrence was highest in patients treated with frontline imatinib not fulfilling TFR recommendations and lowest in patients treated with a second-generation TKI and who fulfilled the eligibility criteria.

Study details: This retrospective study assessed TFR eligibility and outcomes in 398 patients with newly diagnosed CML-CP treated with either imatinib (73%) or a second- or third-generation TKI (27%) as frontline therapy.

Disclosures: No specific funding source was identified. Some investigators including the lead author reported ties with various pharmaceutical companies. The authors declared no conflicts of interest.

Source: Etienne G et al. Cancer Med. 2021 May 14. doi: 10.1002/cam4.3921.

Key clinical point: Patients with chronic-phase chronic myeloid leukemia (CML-CP) receiving a second-generation tyrosine kinase inhibitor (TKI) frontline and fulfilling eligibility criteria for European LeukemiaNet 2020 treatment-free remission (TFR) recommendations had the highest molecular recurrence-free survival (MRFS) after TKI discontinuation.

Major finding: MRFS at 2 and 5 years were 51.8% and 43.8%, respectively. MRFS was significantly higher in patients who fulfilled TFR recommendations vs. those who did not (P = .005). Molecular recurrence was highest in patients treated with frontline imatinib not fulfilling TFR recommendations and lowest in patients treated with a second-generation TKI and who fulfilled the eligibility criteria.

Study details: This retrospective study assessed TFR eligibility and outcomes in 398 patients with newly diagnosed CML-CP treated with either imatinib (73%) or a second- or third-generation TKI (27%) as frontline therapy.

Disclosures: No specific funding source was identified. Some investigators including the lead author reported ties with various pharmaceutical companies. The authors declared no conflicts of interest.

Source: Etienne G et al. Cancer Med. 2021 May 14. doi: 10.1002/cam4.3921.

Key clinical point: Patients with chronic-phase chronic myeloid leukemia (CML-CP) receiving a second-generation tyrosine kinase inhibitor (TKI) frontline and fulfilling eligibility criteria for European LeukemiaNet 2020 treatment-free remission (TFR) recommendations had the highest molecular recurrence-free survival (MRFS) after TKI discontinuation.

Major finding: MRFS at 2 and 5 years were 51.8% and 43.8%, respectively. MRFS was significantly higher in patients who fulfilled TFR recommendations vs. those who did not (P = .005). Molecular recurrence was highest in patients treated with frontline imatinib not fulfilling TFR recommendations and lowest in patients treated with a second-generation TKI and who fulfilled the eligibility criteria.

Study details: This retrospective study assessed TFR eligibility and outcomes in 398 patients with newly diagnosed CML-CP treated with either imatinib (73%) or a second- or third-generation TKI (27%) as frontline therapy.

Disclosures: No specific funding source was identified. Some investigators including the lead author reported ties with various pharmaceutical companies. The authors declared no conflicts of interest.

Source: Etienne G et al. Cancer Med. 2021 May 14. doi: 10.1002/cam4.3921.

Key clinical point: Cognitive behavioral therapy for targeted therapy-related fatigue (CBT-TTF) improved tyrosine kinase inhibitor (TKI)-related fatigue in patients with chronic-phase chronic myeloid leukemia (CML-CP).

Major finding: Patients receiving 18-week CBT-TTF vs. control reported improvements in physical (P = .023), mental (P = .015), and social activity (P = .001), along with enhanced cognitions including self-efficacy (P = .001), helplessness (P = .003), fatigue catastrophizing and focusing on symptoms (both P less than .001).

Study details: Findings are from secondary analysis of a trial including 36 adults with CML-CP treated with a TKI, who reported moderate to severe fatigue and were randomly allocated to receive either CBT-TTF (n=22) or waitlist control (n=14).

Disclosures: This study was funded by the National Cancer Institute. Some coinvestigators reported grants, consultancy, advisory, and speakers’ bureau memberships from various pharmaceutical companies.

Source: Hyland KA et al. Ann Behav Med. 2021 May 15. doi: 10.1093/abm/kaab035.

Key clinical point: Cognitive behavioral therapy for targeted therapy-related fatigue (CBT-TTF) improved tyrosine kinase inhibitor (TKI)-related fatigue in patients with chronic-phase chronic myeloid leukemia (CML-CP).

Major finding: Patients receiving 18-week CBT-TTF vs. control reported improvements in physical (P = .023), mental (P = .015), and social activity (P = .001), along with enhanced cognitions including self-efficacy (P = .001), helplessness (P = .003), fatigue catastrophizing and focusing on symptoms (both P less than .001).

Study details: Findings are from secondary analysis of a trial including 36 adults with CML-CP treated with a TKI, who reported moderate to severe fatigue and were randomly allocated to receive either CBT-TTF (n=22) or waitlist control (n=14).

Disclosures: This study was funded by the National Cancer Institute. Some coinvestigators reported grants, consultancy, advisory, and speakers’ bureau memberships from various pharmaceutical companies.

Source: Hyland KA et al. Ann Behav Med. 2021 May 15. doi: 10.1093/abm/kaab035.

Key clinical point: Cognitive behavioral therapy for targeted therapy-related fatigue (CBT-TTF) improved tyrosine kinase inhibitor (TKI)-related fatigue in patients with chronic-phase chronic myeloid leukemia (CML-CP).

Major finding: Patients receiving 18-week CBT-TTF vs. control reported improvements in physical (P = .023), mental (P = .015), and social activity (P = .001), along with enhanced cognitions including self-efficacy (P = .001), helplessness (P = .003), fatigue catastrophizing and focusing on symptoms (both P less than .001).

Study details: Findings are from secondary analysis of a trial including 36 adults with CML-CP treated with a TKI, who reported moderate to severe fatigue and were randomly allocated to receive either CBT-TTF (n=22) or waitlist control (n=14).

Disclosures: This study was funded by the National Cancer Institute. Some coinvestigators reported grants, consultancy, advisory, and speakers’ bureau memberships from various pharmaceutical companies.

Source: Hyland KA et al. Ann Behav Med. 2021 May 15. doi: 10.1093/abm/kaab035.

Background: With more than 500 cases of NSF reported during 1997-2007, a black box warning advises against use of all GBCAs in at-risk CKD patients. However, newer literature has shown that group II GBCAs may have lower risks of causing NSF. The risk to patients with CKD IV and V is not clear.

Dr. Midha is a hospitalist at Beth Israel Deaconess Medical Center, instructor of medicine, Boston University, and part-time instructor in medicine, Harvard Medical School, all in Boston.

Background: With more than 500 cases of NSF reported during 1997-2007, a black box warning advises against use of all GBCAs in at-risk CKD patients. However, newer literature has shown that group II GBCAs may have lower risks of causing NSF. The risk to patients with CKD IV and V is not clear.

Dr. Midha is a hospitalist at Beth Israel Deaconess Medical Center, instructor of medicine, Boston University, and part-time instructor in medicine, Harvard Medical School, all in Boston.

Background: With more than 500 cases of NSF reported during 1997-2007, a black box warning advises against use of all GBCAs in at-risk CKD patients. However, newer literature has shown that group II GBCAs may have lower risks of causing NSF. The risk to patients with CKD IV and V is not clear.

Dr. Midha is a hospitalist at Beth Israel Deaconess Medical Center, instructor of medicine, Boston University, and part-time instructor in medicine, Harvard Medical School, all in Boston.

Key clinical point: Findings from routine clinical practice are in concordance with results from clinical trials and confirm the efficacy of ponatinib in patients with chronic myeloid leukemia (CML) who were resistant or intolerant to previous tyrosine kinase inhibitors (TKIs) or had T315I mutation. No new safety signals were identified.

Major finding: During a median follow-up of 15 months, major molecular response was achieved in 58% of patients with CML. Estimated 3-year overall survival and progression-free survival were 85.3% and 81.6%, respectively. Treatment termination because of adverse events occurred in 8 patients with CML.

Study details: Findings are from a prospective observational study including 33 patients with CML and 17 patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Patients were initiated on ponatinib following intolerance, relapse, or refractoriness to prior TKIs, disease progression, or T315I mutation.

Disclosures: This study was funded by Incyte Biosciences Benelux BV. Some investigators reported research funding, advisory board memberships, consultancy, honoraria, travel expenses, and membership of the board of directors for various pharmaceutical companies including Incyte Biosciences Benelux BV.

Source: Devos T et al. Ann Hematol. 2021 May 4. doi: 10.1007/s00277-021-04507-x.

Key clinical point: Findings from routine clinical practice are in concordance with results from clinical trials and confirm the efficacy of ponatinib in patients with chronic myeloid leukemia (CML) who were resistant or intolerant to previous tyrosine kinase inhibitors (TKIs) or had T315I mutation. No new safety signals were identified.

Major finding: During a median follow-up of 15 months, major molecular response was achieved in 58% of patients with CML. Estimated 3-year overall survival and progression-free survival were 85.3% and 81.6%, respectively. Treatment termination because of adverse events occurred in 8 patients with CML.

Study details: Findings are from a prospective observational study including 33 patients with CML and 17 patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Patients were initiated on ponatinib following intolerance, relapse, or refractoriness to prior TKIs, disease progression, or T315I mutation.

Disclosures: This study was funded by Incyte Biosciences Benelux BV. Some investigators reported research funding, advisory board memberships, consultancy, honoraria, travel expenses, and membership of the board of directors for various pharmaceutical companies including Incyte Biosciences Benelux BV.

Source: Devos T et al. Ann Hematol. 2021 May 4. doi: 10.1007/s00277-021-04507-x.

Key clinical point: Findings from routine clinical practice are in concordance with results from clinical trials and confirm the efficacy of ponatinib in patients with chronic myeloid leukemia (CML) who were resistant or intolerant to previous tyrosine kinase inhibitors (TKIs) or had T315I mutation. No new safety signals were identified.

Major finding: During a median follow-up of 15 months, major molecular response was achieved in 58% of patients with CML. Estimated 3-year overall survival and progression-free survival were 85.3% and 81.6%, respectively. Treatment termination because of adverse events occurred in 8 patients with CML.

Study details: Findings are from a prospective observational study including 33 patients with CML and 17 patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Patients were initiated on ponatinib following intolerance, relapse, or refractoriness to prior TKIs, disease progression, or T315I mutation.

Disclosures: This study was funded by Incyte Biosciences Benelux BV. Some investigators reported research funding, advisory board memberships, consultancy, honoraria, travel expenses, and membership of the board of directors for various pharmaceutical companies including Incyte Biosciences Benelux BV.

Source: Devos T et al. Ann Hematol. 2021 May 4. doi: 10.1007/s00277-021-04507-x.

Key clinical point: Single nucleotide polymorphisms (SNPs) in the major multidrug resistance (MDR)-ATP-binding cassette (ABC) transporter genes, ABCB1, ABCC2, and ABCG2, influenced the achievement of molecular response (MR)3 and MR4 in patients with chronic-phase chronic myeloid leukemia (CML-CP) treated with nilotinib.

Major finding: Patients with ABCB1 rs1045642 TT (P = .01) or ABCC2 rs3740066 CT (P = .004) and CC (P = .02) genotypes achieved significantly higher rates of MR3 in a shorter period. Conversely, patients with ABCG2 rs2231137 GG genotype had a lower probability of achieving MR3 (P = .005). ABCC2 rs3740066 CC (P = .02) and ABCB1 rs1045642 CC (P = .007) and TT (P = .003) genotypes were associated with higher rates of MR4 achievement.

Study details: This observational study assessed 7 SNPs in 4 ABC transporter genes (ABCB1, ABCC1, ABCC2, and ABCG2) in 90 Caucasian adult patients with CML-CP treated with first-or second-line nilotinib.

Disclosures: This study was supported in part by AIL Pesaro Onlus. The authors declared no conflicts of interest.

Source: Loscocco F et al. Front Oncol. 2021 May 13. doi: 10.3389/fonc.2021.672287.

Key clinical point: Single nucleotide polymorphisms (SNPs) in the major multidrug resistance (MDR)-ATP-binding cassette (ABC) transporter genes, ABCB1, ABCC2, and ABCG2, influenced the achievement of molecular response (MR)3 and MR4 in patients with chronic-phase chronic myeloid leukemia (CML-CP) treated with nilotinib.

Major finding: Patients with ABCB1 rs1045642 TT (P = .01) or ABCC2 rs3740066 CT (P = .004) and CC (P = .02) genotypes achieved significantly higher rates of MR3 in a shorter period. Conversely, patients with ABCG2 rs2231137 GG genotype had a lower probability of achieving MR3 (P = .005). ABCC2 rs3740066 CC (P = .02) and ABCB1 rs1045642 CC (P = .007) and TT (P = .003) genotypes were associated with higher rates of MR4 achievement.

Study details: This observational study assessed 7 SNPs in 4 ABC transporter genes (ABCB1, ABCC1, ABCC2, and ABCG2) in 90 Caucasian adult patients with CML-CP treated with first-or second-line nilotinib.

Disclosures: This study was supported in part by AIL Pesaro Onlus. The authors declared no conflicts of interest.

Source: Loscocco F et al. Front Oncol. 2021 May 13. doi: 10.3389/fonc.2021.672287.

Key clinical point: Single nucleotide polymorphisms (SNPs) in the major multidrug resistance (MDR)-ATP-binding cassette (ABC) transporter genes, ABCB1, ABCC2, and ABCG2, influenced the achievement of molecular response (MR)3 and MR4 in patients with chronic-phase chronic myeloid leukemia (CML-CP) treated with nilotinib.

Major finding: Patients with ABCB1 rs1045642 TT (P = .01) or ABCC2 rs3740066 CT (P = .004) and CC (P = .02) genotypes achieved significantly higher rates of MR3 in a shorter period. Conversely, patients with ABCG2 rs2231137 GG genotype had a lower probability of achieving MR3 (P = .005). ABCC2 rs3740066 CC (P = .02) and ABCB1 rs1045642 CC (P = .007) and TT (P = .003) genotypes were associated with higher rates of MR4 achievement.

Study details: This observational study assessed 7 SNPs in 4 ABC transporter genes (ABCB1, ABCC1, ABCC2, and ABCG2) in 90 Caucasian adult patients with CML-CP treated with first-or second-line nilotinib.

Disclosures: This study was supported in part by AIL Pesaro Onlus. The authors declared no conflicts of interest.

Source: Loscocco F et al. Front Oncol. 2021 May 13. doi: 10.3389/fonc.2021.672287.

Key clinical point: In patients with chronic-phase chronic myeloid leukemia (CML-CP), imatinib treatment for at least 6 years and molecular response 4 (MR4) duration of a minimum of 4.5 years may be optimal for higher treatment-free remission (TFR) success after imatinib discontinuation.

Major finding: Patients with imatinib treatment duration of 6 years or more vs. less than 6 years (61.8% vs. 36.0%; P = .01) and those with MR4 duration of 4.5 years or longer vs. less than 4.5 years (64.2% vs. 41.9%; P = .003) had a superior molecular relapse-free survival at 12 months after imatinib discontinuation.

Study details: This prospective study reported findings from the TRAD study including 131 patients with CML-CP. Patients were treated with imatinib for at least 3 years (range, 3.0-17.5 years) and had a minimum of 2 years of MR4 or deeper response (range, 2.0-15.8 years) before imatinib discontinuation.

Disclosures: This study was supported by BMS Canada and the Princess Margaret Cancer Foundation. The lead author reported research funding from BMS and Novartis.

Source: Kim DDH et al. Br J Haematol. 2021 Apr 20. doi: 10.1111/bjh.17447.

Key clinical point: In patients with chronic-phase chronic myeloid leukemia (CML-CP), imatinib treatment for at least 6 years and molecular response 4 (MR4) duration of a minimum of 4.5 years may be optimal for higher treatment-free remission (TFR) success after imatinib discontinuation.

Major finding: Patients with imatinib treatment duration of 6 years or more vs. less than 6 years (61.8% vs. 36.0%; P = .01) and those with MR4 duration of 4.5 years or longer vs. less than 4.5 years (64.2% vs. 41.9%; P = .003) had a superior molecular relapse-free survival at 12 months after imatinib discontinuation.

Study details: This prospective study reported findings from the TRAD study including 131 patients with CML-CP. Patients were treated with imatinib for at least 3 years (range, 3.0-17.5 years) and had a minimum of 2 years of MR4 or deeper response (range, 2.0-15.8 years) before imatinib discontinuation.

Disclosures: This study was supported by BMS Canada and the Princess Margaret Cancer Foundation. The lead author reported research funding from BMS and Novartis.

Source: Kim DDH et al. Br J Haematol. 2021 Apr 20. doi: 10.1111/bjh.17447.

Key clinical point: In patients with chronic-phase chronic myeloid leukemia (CML-CP), imatinib treatment for at least 6 years and molecular response 4 (MR4) duration of a minimum of 4.5 years may be optimal for higher treatment-free remission (TFR) success after imatinib discontinuation.

Major finding: Patients with imatinib treatment duration of 6 years or more vs. less than 6 years (61.8% vs. 36.0%; P = .01) and those with MR4 duration of 4.5 years or longer vs. less than 4.5 years (64.2% vs. 41.9%; P = .003) had a superior molecular relapse-free survival at 12 months after imatinib discontinuation.

Study details: This prospective study reported findings from the TRAD study including 131 patients with CML-CP. Patients were treated with imatinib for at least 3 years (range, 3.0-17.5 years) and had a minimum of 2 years of MR4 or deeper response (range, 2.0-15.8 years) before imatinib discontinuation.

Disclosures: This study was supported by BMS Canada and the Princess Margaret Cancer Foundation. The lead author reported research funding from BMS and Novartis.

Source: Kim DDH et al. Br J Haematol. 2021 Apr 20. doi: 10.1111/bjh.17447.

Key clinical point: Response and survival with current therapies remain poor in patients with atypical chronic myeloid leukemia (aCML), with allogeneic stem cell transplantation (allo-SCT) being the only treatment associated with improved survival.

Major finding: Overall response rate was 29%, with only 3 patients achieving a complete response. The median overall survival (OS) was 25 (95% confidence interval, 20.0-30.0) months, with OS being worst in patients receiving intensive chemotherapy than those receiving hypomethylating agents, ruxolitinib, or hydroxyurea. Allo-SCT was associated with improved survival (hazard ratio, 0.144; P = .007).

Study details: This retrospective study included 65 patients (median age, 67 years) with aCML.

Disclosures: This study was funded by grants from The University of Texas MD Anderson Cancer Center. Some investigators reported financial and/or nonfinancial ties with various pharmaceutical companies.

Source: Montalban-Bravo G et al. Cancer. 2021 Apr 29. doi: 10.1002/cncr.33622.

Key clinical point: Response and survival with current therapies remain poor in patients with atypical chronic myeloid leukemia (aCML), with allogeneic stem cell transplantation (allo-SCT) being the only treatment associated with improved survival.

Major finding: Overall response rate was 29%, with only 3 patients achieving a complete response. The median overall survival (OS) was 25 (95% confidence interval, 20.0-30.0) months, with OS being worst in patients receiving intensive chemotherapy than those receiving hypomethylating agents, ruxolitinib, or hydroxyurea. Allo-SCT was associated with improved survival (hazard ratio, 0.144; P = .007).

Study details: This retrospective study included 65 patients (median age, 67 years) with aCML.

Disclosures: This study was funded by grants from The University of Texas MD Anderson Cancer Center. Some investigators reported financial and/or nonfinancial ties with various pharmaceutical companies.

Source: Montalban-Bravo G et al. Cancer. 2021 Apr 29. doi: 10.1002/cncr.33622.

Key clinical point: Response and survival with current therapies remain poor in patients with atypical chronic myeloid leukemia (aCML), with allogeneic stem cell transplantation (allo-SCT) being the only treatment associated with improved survival.

Major finding: Overall response rate was 29%, with only 3 patients achieving a complete response. The median overall survival (OS) was 25 (95% confidence interval, 20.0-30.0) months, with OS being worst in patients receiving intensive chemotherapy than those receiving hypomethylating agents, ruxolitinib, or hydroxyurea. Allo-SCT was associated with improved survival (hazard ratio, 0.144; P = .007).

Study details: This retrospective study included 65 patients (median age, 67 years) with aCML.

Disclosures: This study was funded by grants from The University of Texas MD Anderson Cancer Center. Some investigators reported financial and/or nonfinancial ties with various pharmaceutical companies.

Source: Montalban-Bravo G et al. Cancer. 2021 Apr 29. doi: 10.1002/cncr.33622.

Key clinical point: Treatment-free remission (TFR) was durable in a large proportion of patients with chronic-phase chronic myeloid leukemia (CML-CP) who switched to nilotinib from imatinib. However, careful management of adverse events (AEs) is required in patients reinitiating nilotinib after TFR.

Major finding: At 5 years, the rate of successful TFR and overall survival was 42.9% and 95.9%, respectively. Of 59 patients reinitiating nilotinib, 98.3% of patients regained major molecular response. Overall, AEs increased in nilotinib reinitiation vs. consolidation phase (67.8% vs. 28.2%) including a higher frequency of cardiovascular events (27.1% vs. 6.1%).

Study details: Findings are from an updated analysis of phase 2 ENESTop trial including patients with CML-CP who achieved sustained deep molecular response only after switching from imatinib to nilotinib. TFR was attempted by 126 patients following 1 year of nilotinib consolidation phase.

Disclosures: This study was funded by Novartis Pharmaceuticals. The lead author reported financial and nonfinancial ties with Bristol Myers Squibb and Novartis. Some investigators reported ties with various pharmaceutical companies including Novartis.

Source: Hughes TP et al. Leukemia. 2021 May 12. doi: 10.1038/s41375-021-01260-y.

Key clinical point: Treatment-free remission (TFR) was durable in a large proportion of patients with chronic-phase chronic myeloid leukemia (CML-CP) who switched to nilotinib from imatinib. However, careful management of adverse events (AEs) is required in patients reinitiating nilotinib after TFR.

Major finding: At 5 years, the rate of successful TFR and overall survival was 42.9% and 95.9%, respectively. Of 59 patients reinitiating nilotinib, 98.3% of patients regained major molecular response. Overall, AEs increased in nilotinib reinitiation vs. consolidation phase (67.8% vs. 28.2%) including a higher frequency of cardiovascular events (27.1% vs. 6.1%).

Study details: Findings are from an updated analysis of phase 2 ENESTop trial including patients with CML-CP who achieved sustained deep molecular response only after switching from imatinib to nilotinib. TFR was attempted by 126 patients following 1 year of nilotinib consolidation phase.

Disclosures: This study was funded by Novartis Pharmaceuticals. The lead author reported financial and nonfinancial ties with Bristol Myers Squibb and Novartis. Some investigators reported ties with various pharmaceutical companies including Novartis.

Source: Hughes TP et al. Leukemia. 2021 May 12. doi: 10.1038/s41375-021-01260-y.

Key clinical point: Treatment-free remission (TFR) was durable in a large proportion of patients with chronic-phase chronic myeloid leukemia (CML-CP) who switched to nilotinib from imatinib. However, careful management of adverse events (AEs) is required in patients reinitiating nilotinib after TFR.

Major finding: At 5 years, the rate of successful TFR and overall survival was 42.9% and 95.9%, respectively. Of 59 patients reinitiating nilotinib, 98.3% of patients regained major molecular response. Overall, AEs increased in nilotinib reinitiation vs. consolidation phase (67.8% vs. 28.2%) including a higher frequency of cardiovascular events (27.1% vs. 6.1%).

Study details: Findings are from an updated analysis of phase 2 ENESTop trial including patients with CML-CP who achieved sustained deep molecular response only after switching from imatinib to nilotinib. TFR was attempted by 126 patients following 1 year of nilotinib consolidation phase.

Disclosures: This study was funded by Novartis Pharmaceuticals. The lead author reported financial and nonfinancial ties with Bristol Myers Squibb and Novartis. Some investigators reported ties with various pharmaceutical companies including Novartis.

Source: Hughes TP et al. Leukemia. 2021 May 12. doi: 10.1038/s41375-021-01260-y.

Key clinical point: In patients with chronic myeloid leukemia (CML), the transformation from chronic phase (CP) to blast crisis (BC) was associated with accumulation of somatic mutations with time in the absence of effective therapy, which may be suppressed by tyrosine kinase inhibitor (TKI) therapy, thereby preventing disease progression.

Major finding: The number of genetic alterations increased during CP to BC progression with a mean of 5.3 nonsynonymous single-nucleotide variants acquired. The number of mutations acquired during CP to BC progression was positively correlated with interval between progression (P = 9.4×10⁻¹²) and negatively correlated with TKI therapy after CP diagnosis (P = 9.3×10⁻³).

Study details: This study used exome and targeted sequencing to evaluate genetic alterations in 136 BC and 148 CP samples from 216 patients with CML.

Disclosures: This work was supported by the Grant-in-Aid for JSPS KAKENHI and Scientific Research on Innovative Areas and grants from AMED, MEXT, “Stem Cell Aging and Disease,” Takeda Science Foundation, Ministry of Science and Technology (Taiwan), and others. S Bradford reported ties with various pharmaceutical companies. Other authors declared no conflicts of interest.

Source: Ochi Y et al. Nat Commun. 2021 May 14. doi: 10.1038/s41467-021-23097-w.

Key clinical point: In patients with chronic myeloid leukemia (CML), the transformation from chronic phase (CP) to blast crisis (BC) was associated with accumulation of somatic mutations with time in the absence of effective therapy, which may be suppressed by tyrosine kinase inhibitor (TKI) therapy, thereby preventing disease progression.

Major finding: The number of genetic alterations increased during CP to BC progression with a mean of 5.3 nonsynonymous single-nucleotide variants acquired. The number of mutations acquired during CP to BC progression was positively correlated with interval between progression (P = 9.4×10⁻¹²) and negatively correlated with TKI therapy after CP diagnosis (P = 9.3×10⁻³).

Study details: This study used exome and targeted sequencing to evaluate genetic alterations in 136 BC and 148 CP samples from 216 patients with CML.

Disclosures: This work was supported by the Grant-in-Aid for JSPS KAKENHI and Scientific Research on Innovative Areas and grants from AMED, MEXT, “Stem Cell Aging and Disease,” Takeda Science Foundation, Ministry of Science and Technology (Taiwan), and others. S Bradford reported ties with various pharmaceutical companies. Other authors declared no conflicts of interest.

Source: Ochi Y et al. Nat Commun. 2021 May 14. doi: 10.1038/s41467-021-23097-w.

Key clinical point: In patients with chronic myeloid leukemia (CML), the transformation from chronic phase (CP) to blast crisis (BC) was associated with accumulation of somatic mutations with time in the absence of effective therapy, which may be suppressed by tyrosine kinase inhibitor (TKI) therapy, thereby preventing disease progression.

Major finding: The number of genetic alterations increased during CP to BC progression with a mean of 5.3 nonsynonymous single-nucleotide variants acquired. The number of mutations acquired during CP to BC progression was positively correlated with interval between progression (P = 9.4×10⁻¹²) and negatively correlated with TKI therapy after CP diagnosis (P = 9.3×10⁻³).

Study details: This study used exome and targeted sequencing to evaluate genetic alterations in 136 BC and 148 CP samples from 216 patients with CML.

Disclosures: This work was supported by the Grant-in-Aid for JSPS KAKENHI and Scientific Research on Innovative Areas and grants from AMED, MEXT, “Stem Cell Aging and Disease,” Takeda Science Foundation, Ministry of Science and Technology (Taiwan), and others. S Bradford reported ties with various pharmaceutical companies. Other authors declared no conflicts of interest.

Source: Ochi Y et al. Nat Commun. 2021 May 14. doi: 10.1038/s41467-021-23097-w.

In a comprehensive and detailed analysis, Ochi et al evaluated the genetic alterations in 136 blast crisis (BC) and 148 chronic phase (CP) samples from 216 patients with chronic myeloid leukemia (CML) by exome and targeted sequencing. The number of genetic alterations increased during CP to BC progression with a mean of 5.3 nonsynonymous single-nucleotide variants acquired. One or more genetic abnormalities are found in 126 (92.6%) out of the 136 BC patients. As expected, the lineage of the BC and prior use of tyrosine kinase inhibitors (TKIs) correlate with distinct molecular profiles. TKIs markedly suppressed the number of genetic alterations increase during the transition from CP to BC. Notably, genetic alterations such AXL1 mutations complex CNAs, i(17q), and +21, rather than clinical variables, contribute to a better prediction of BC prognosis in early therapy with TKI in CP.

Switching to a second generation TKI with the goal of obtaining a deeper response and therefore a chance for treatment-free remission (TFR), is an option for certain patients and has been investigated in a few trials. ENEStop may be the most popular and Hughes et al had updated the 5 years follow up in a recent publication. The study includes patients with chronic-phase chronic myeloid leukemia (CML-CP)  who achieved sustained deep molecular response only after switching from imatinib to nilotinib and TFR was attempted by 126 patients following 1 year of nilotinib consolidation phase. At 5 years, the rate of successful TFR and overall survival was 42.9% and 95.9%, respectively. Of 59 patients reinitiating nilotinib, 98.3% of patients regained major molecular response. Overall, AEs increased in nilotinib reinitiation vs. consolidation phase including cardiovascular (CV) adverse events (AEs) as patients had a long duration of exposure for nilotinib.

After several publications and recommendations by NCCN and ELN, the optimal cut-off values of the duration of MR4 and deeper responses remain unresolved. Kim et al reported a large study of 131 patients enrolled into the Canadian TKI discontinuation study and evaluated the molecular relapse-free survival (mRFS) at 12 months after imatinib discontinuation. Based on this analysis they propose 6 years with imatinib treatment duration as the shortest imatinib duration- a superior success versus less than 6 years (61.8% vs. 36.0%; P = .01). Also a MR4 duration of 4.5 years or longer vs. less than 4.5 years (64.2% vs. 41.9%; P = .003) was associated with a superior molecular relapse-free survival at 12 months after imatinib discontinuation.

Fatigue is a common complain of patients taking TKI and has been well reported as adverse effects in most of the CML trials. However, when evaluating fatigue, it is always difficult to understand if there are additional factors that can contribute to it. Hyland et al investigated if the use of cognitive behavioral therapy for targeted-therapy related fatigue (CBT-TTF) targeting fatigue perpetuating factors change over time. By delivering CBT via FaceTime or wait list control in CML patients with moderate or severe fatigue, they were able to see an improvement in TKI-related fatigue in CML patients through changes in behavior (sleep, activity patterns) and cognitions about fatigue and cancer.

In a comprehensive and detailed analysis, Ochi et al evaluated the genetic alterations in 136 blast crisis (BC) and 148 chronic phase (CP) samples from 216 patients with chronic myeloid leukemia (CML) by exome and targeted sequencing. The number of genetic alterations increased during CP to BC progression with a mean of 5.3 nonsynonymous single-nucleotide variants acquired. One or more genetic abnormalities are found in 126 (92.6%) out of the 136 BC patients. As expected, the lineage of the BC and prior use of tyrosine kinase inhibitors (TKIs) correlate with distinct molecular profiles. TKIs markedly suppressed the number of genetic alterations increase during the transition from CP to BC. Notably, genetic alterations such AXL1 mutations complex CNAs, i(17q), and +21, rather than clinical variables, contribute to a better prediction of BC prognosis in early therapy with TKI in CP.

Switching to a second generation TKI with the goal of obtaining a deeper response and therefore a chance for treatment-free remission (TFR), is an option for certain patients and has been investigated in a few trials. ENEStop may be the most popular and Hughes et al had updated the 5 years follow up in a recent publication. The study includes patients with chronic-phase chronic myeloid leukemia (CML-CP)  who achieved sustained deep molecular response only after switching from imatinib to nilotinib and TFR was attempted by 126 patients following 1 year of nilotinib consolidation phase. At 5 years, the rate of successful TFR and overall survival was 42.9% and 95.9%, respectively. Of 59 patients reinitiating nilotinib, 98.3% of patients regained major molecular response. Overall, AEs increased in nilotinib reinitiation vs. consolidation phase including cardiovascular (CV) adverse events (AEs) as patients had a long duration of exposure for nilotinib.

After several publications and recommendations by NCCN and ELN, the optimal cut-off values of the duration of MR4 and deeper responses remain unresolved. Kim et al reported a large study of 131 patients enrolled into the Canadian TKI discontinuation study and evaluated the molecular relapse-free survival (mRFS) at 12 months after imatinib discontinuation. Based on this analysis they propose 6 years with imatinib treatment duration as the shortest imatinib duration- a superior success versus less than 6 years (61.8% vs. 36.0%; P = .01). Also a MR4 duration of 4.5 years or longer vs. less than 4.5 years (64.2% vs. 41.9%; P = .003) was associated with a superior molecular relapse-free survival at 12 months after imatinib discontinuation.

Fatigue is a common complain of patients taking TKI and has been well reported as adverse effects in most of the CML trials. However, when evaluating fatigue, it is always difficult to understand if there are additional factors that can contribute to it. Hyland et al investigated if the use of cognitive behavioral therapy for targeted-therapy related fatigue (CBT-TTF) targeting fatigue perpetuating factors change over time. By delivering CBT via FaceTime or wait list control in CML patients with moderate or severe fatigue, they were able to see an improvement in TKI-related fatigue in CML patients through changes in behavior (sleep, activity patterns) and cognitions about fatigue and cancer.

In a comprehensive and detailed analysis, Ochi et al evaluated the genetic alterations in 136 blast crisis (BC) and 148 chronic phase (CP) samples from 216 patients with chronic myeloid leukemia (CML) by exome and targeted sequencing. The number of genetic alterations increased during CP to BC progression with a mean of 5.3 nonsynonymous single-nucleotide variants acquired. One or more genetic abnormalities are found in 126 (92.6%) out of the 136 BC patients. As expected, the lineage of the BC and prior use of tyrosine kinase inhibitors (TKIs) correlate with distinct molecular profiles. TKIs markedly suppressed the number of genetic alterations increase during the transition from CP to BC. Notably, genetic alterations such AXL1 mutations complex CNAs, i(17q), and +21, rather than clinical variables, contribute to a better prediction of BC prognosis in early therapy with TKI in CP.

Switching to a second generation TKI with the goal of obtaining a deeper response and therefore a chance for treatment-free remission (TFR), is an option for certain patients and has been investigated in a few trials. ENEStop may be the most popular and Hughes et al had updated the 5 years follow up in a recent publication. The study includes patients with chronic-phase chronic myeloid leukemia (CML-CP)  who achieved sustained deep molecular response only after switching from imatinib to nilotinib and TFR was attempted by 126 patients following 1 year of nilotinib consolidation phase. At 5 years, the rate of successful TFR and overall survival was 42.9% and 95.9%, respectively. Of 59 patients reinitiating nilotinib, 98.3% of patients regained major molecular response. Overall, AEs increased in nilotinib reinitiation vs. consolidation phase including cardiovascular (CV) adverse events (AEs) as patients had a long duration of exposure for nilotinib.

After several publications and recommendations by NCCN and ELN, the optimal cut-off values of the duration of MR4 and deeper responses remain unresolved. Kim et al reported a large study of 131 patients enrolled into the Canadian TKI discontinuation study and evaluated the molecular relapse-free survival (mRFS) at 12 months after imatinib discontinuation. Based on this analysis they propose 6 years with imatinib treatment duration as the shortest imatinib duration- a superior success versus less than 6 years (61.8% vs. 36.0%; P = .01). Also a MR4 duration of 4.5 years or longer vs. less than 4.5 years (64.2% vs. 41.9%; P = .003) was associated with a superior molecular relapse-free survival at 12 months after imatinib discontinuation.

Fatigue is a common complain of patients taking TKI and has been well reported as adverse effects in most of the CML trials. However, when evaluating fatigue, it is always difficult to understand if there are additional factors that can contribute to it. Hyland et al investigated if the use of cognitive behavioral therapy for targeted-therapy related fatigue (CBT-TTF) targeting fatigue perpetuating factors change over time. By delivering CBT via FaceTime or wait list control in CML patients with moderate or severe fatigue, they were able to see an improvement in TKI-related fatigue in CML patients through changes in behavior (sleep, activity patterns) and cognitions about fatigue and cancer.