CML

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.

Survivors of childhood cancers are at increased risk for prescription opioid misuse compared with their peers, a review of a claims database revealed.

Among more than 8,000 patients age 21 or younger who had completed treatment for hematologic, central nervous system, bone, or gonadal cancers, survivors were significantly more likely than were their peers to have an opioid prescription, longer duration of prescription, and higher daily doses of opioids, and to have opioid prescriptions overlapping for a week or more, reported Xu Ji, PhD, of Emory University in Atlanta.

Teenage and young adult patients were at higher risk than were patients younger than 12, and the risk was highest among patients who had been treated for bone malignancies, as well as those who had undergone any hematopoietic stem cell transplant.

“These findings suggest that health care providers who regularly see survivors should explore nonopioid options to help prevent opioid misuse, and screen for potential misuse in those who actually receive opioids,” she said in an oral abstract presented during the annual meeting of the American Society of Pediatric Hematology/Oncology.

“This is a really important topic, and something that’s probably been underinvestigated and underexplored in our patient population,” said session comoderator Sheri Spunt, MD, Endowed Professor of Pediatric Cancer at Stanford (Calif.) University.
 

Database review

Dr. Ji and colleagues used the IBM MarketScan Commercial Claims and Encounters database from 2009 to 2018 to examine prescription opioid use, potential misuse, and substance use disorders in pediatric cancer survivors in the first year after completion of therapy, and to identify factors associated with risk for misuse or substance use disorders. Specifically, the period of interest was the first year after completion of all treatments, including surgery, chemotherapy, radiation, and stem cell transplant (Abstract 2015).

They looked at deidentified records on any opioid prescription and for treatment of any opioid use or substance use disorder (alcohol, psychotherapeutic drugs, marijuana, or illicit drug use disorders).

They defined indicators of potential misuse as either prescriptions for long-acting or extended-release opioids for acute pain conditions; opioid and benzodiazepine prescriptions overlapping by a week or more; opioid prescriptions overlapping by a week or more; high daily opioid dosage (prescribed daily dose of 100 or greater morphine milligram equivalent [MME]; and/or opioid dose escalation (an increase of at least 50% in mean MMEs per month twice consecutively within 1 year).

They compared outcomes between a total of 8,635 survivors and 44,175 controls, matched on a 1:5 basis with survivors by age, sex, and region, and continuous enrollment during the 1-year posttherapy period.

In each of three age categories – 0 to 11 years, 12 to 17 years, and 18 years and older – survivors were significantly more likely to have received an opioid prescription, at 15% for the youngest survivors vs. 2% of controls, 25% vs. 8% for 12- to 17-year-olds, and 28% vs. 12% for those 18 and older (P < .01 for all three comparisons).

Survivors were also significantly more likely to have any indicator of potential misuse (1.6% vs. 0.1%, 4.6% vs. 0.5%, and 7.4% vs. 1.2%, respectively, P < .001 for all) and both the youngest and oldest groups (but not 12- to 17-year-olds) were significantly more like to have opioid or substance use disorder (0.4% vs. 0% for 0-11 years, 5.76% vs. 4.2% for 18 years and older, P < .001 for both).

Among patients with any opioid prescription, survivors were significantly more likely than were controls of any age to have indicators for potential misuse. For example, 13% of survivors aged 18 years and older had prescriptions for high opioid doses, compared with 5% of controls, and 12% had prescription overlap, vs. 2%.

Compared with patients with leukemia, patients treated for bone malignancies had a 6% greater risk for having any indicator of misuse, while patients with other malignancies were at slightly lower risk for misuse than those who completed leukemia therapy.

Patients who received any stem cell transplant had an 8.4% greater risk for misuse compared with patients who had surgery only.
 

Opioids pre- and posttreatment?

“Being someone who takes care of a lot of bone cancer patients, I do see patients with these issues,” Dr. Spunt said.

Audience member Jack H. Staddon, MD, PhD, of the Billings (Montana) Clinic, noted the possibility that opioid use during treatment may have been carried on into the posttreatment period, and asked whether use of narcotics during treatment was an independent risk factor for posttreatment narcotic use or misuse.

The researchers plan to investigate this question in future studies, Dr. Ji replied.

They did not report a study funding source. Dr. Ji and coauthors and Dr. Staddon reported no relevant disclosures.

Survivors of childhood cancers are at increased risk for prescription opioid misuse compared with their peers, a review of a claims database revealed.

Among more than 8,000 patients age 21 or younger who had completed treatment for hematologic, central nervous system, bone, or gonadal cancers, survivors were significantly more likely than were their peers to have an opioid prescription, longer duration of prescription, and higher daily doses of opioids, and to have opioid prescriptions overlapping for a week or more, reported Xu Ji, PhD, of Emory University in Atlanta.

Teenage and young adult patients were at higher risk than were patients younger than 12, and the risk was highest among patients who had been treated for bone malignancies, as well as those who had undergone any hematopoietic stem cell transplant.

“These findings suggest that health care providers who regularly see survivors should explore nonopioid options to help prevent opioid misuse, and screen for potential misuse in those who actually receive opioids,” she said in an oral abstract presented during the annual meeting of the American Society of Pediatric Hematology/Oncology.

“This is a really important topic, and something that’s probably been underinvestigated and underexplored in our patient population,” said session comoderator Sheri Spunt, MD, Endowed Professor of Pediatric Cancer at Stanford (Calif.) University.
 

Database review

Dr. Ji and colleagues used the IBM MarketScan Commercial Claims and Encounters database from 2009 to 2018 to examine prescription opioid use, potential misuse, and substance use disorders in pediatric cancer survivors in the first year after completion of therapy, and to identify factors associated with risk for misuse or substance use disorders. Specifically, the period of interest was the first year after completion of all treatments, including surgery, chemotherapy, radiation, and stem cell transplant (Abstract 2015).

They looked at deidentified records on any opioid prescription and for treatment of any opioid use or substance use disorder (alcohol, psychotherapeutic drugs, marijuana, or illicit drug use disorders).

They defined indicators of potential misuse as either prescriptions for long-acting or extended-release opioids for acute pain conditions; opioid and benzodiazepine prescriptions overlapping by a week or more; opioid prescriptions overlapping by a week or more; high daily opioid dosage (prescribed daily dose of 100 or greater morphine milligram equivalent [MME]; and/or opioid dose escalation (an increase of at least 50% in mean MMEs per month twice consecutively within 1 year).

They compared outcomes between a total of 8,635 survivors and 44,175 controls, matched on a 1:5 basis with survivors by age, sex, and region, and continuous enrollment during the 1-year posttherapy period.

In each of three age categories – 0 to 11 years, 12 to 17 years, and 18 years and older – survivors were significantly more likely to have received an opioid prescription, at 15% for the youngest survivors vs. 2% of controls, 25% vs. 8% for 12- to 17-year-olds, and 28% vs. 12% for those 18 and older (P < .01 for all three comparisons).

Survivors were also significantly more likely to have any indicator of potential misuse (1.6% vs. 0.1%, 4.6% vs. 0.5%, and 7.4% vs. 1.2%, respectively, P < .001 for all) and both the youngest and oldest groups (but not 12- to 17-year-olds) were significantly more like to have opioid or substance use disorder (0.4% vs. 0% for 0-11 years, 5.76% vs. 4.2% for 18 years and older, P < .001 for both).

Among patients with any opioid prescription, survivors were significantly more likely than were controls of any age to have indicators for potential misuse. For example, 13% of survivors aged 18 years and older had prescriptions for high opioid doses, compared with 5% of controls, and 12% had prescription overlap, vs. 2%.

Compared with patients with leukemia, patients treated for bone malignancies had a 6% greater risk for having any indicator of misuse, while patients with other malignancies were at slightly lower risk for misuse than those who completed leukemia therapy.

Patients who received any stem cell transplant had an 8.4% greater risk for misuse compared with patients who had surgery only.
 

Opioids pre- and posttreatment?

“Being someone who takes care of a lot of bone cancer patients, I do see patients with these issues,” Dr. Spunt said.

Audience member Jack H. Staddon, MD, PhD, of the Billings (Montana) Clinic, noted the possibility that opioid use during treatment may have been carried on into the posttreatment period, and asked whether use of narcotics during treatment was an independent risk factor for posttreatment narcotic use or misuse.

The researchers plan to investigate this question in future studies, Dr. Ji replied.

They did not report a study funding source. Dr. Ji and coauthors and Dr. Staddon reported no relevant disclosures.

Survivors of childhood cancers are at increased risk for prescription opioid misuse compared with their peers, a review of a claims database revealed.

Among more than 8,000 patients age 21 or younger who had completed treatment for hematologic, central nervous system, bone, or gonadal cancers, survivors were significantly more likely than were their peers to have an opioid prescription, longer duration of prescription, and higher daily doses of opioids, and to have opioid prescriptions overlapping for a week or more, reported Xu Ji, PhD, of Emory University in Atlanta.

Teenage and young adult patients were at higher risk than were patients younger than 12, and the risk was highest among patients who had been treated for bone malignancies, as well as those who had undergone any hematopoietic stem cell transplant.

“These findings suggest that health care providers who regularly see survivors should explore nonopioid options to help prevent opioid misuse, and screen for potential misuse in those who actually receive opioids,” she said in an oral abstract presented during the annual meeting of the American Society of Pediatric Hematology/Oncology.

“This is a really important topic, and something that’s probably been underinvestigated and underexplored in our patient population,” said session comoderator Sheri Spunt, MD, Endowed Professor of Pediatric Cancer at Stanford (Calif.) University.
 

Database review

Dr. Ji and colleagues used the IBM MarketScan Commercial Claims and Encounters database from 2009 to 2018 to examine prescription opioid use, potential misuse, and substance use disorders in pediatric cancer survivors in the first year after completion of therapy, and to identify factors associated with risk for misuse or substance use disorders. Specifically, the period of interest was the first year after completion of all treatments, including surgery, chemotherapy, radiation, and stem cell transplant (Abstract 2015).

They looked at deidentified records on any opioid prescription and for treatment of any opioid use or substance use disorder (alcohol, psychotherapeutic drugs, marijuana, or illicit drug use disorders).

They defined indicators of potential misuse as either prescriptions for long-acting or extended-release opioids for acute pain conditions; opioid and benzodiazepine prescriptions overlapping by a week or more; opioid prescriptions overlapping by a week or more; high daily opioid dosage (prescribed daily dose of 100 or greater morphine milligram equivalent [MME]; and/or opioid dose escalation (an increase of at least 50% in mean MMEs per month twice consecutively within 1 year).

They compared outcomes between a total of 8,635 survivors and 44,175 controls, matched on a 1:5 basis with survivors by age, sex, and region, and continuous enrollment during the 1-year posttherapy period.

In each of three age categories – 0 to 11 years, 12 to 17 years, and 18 years and older – survivors were significantly more likely to have received an opioid prescription, at 15% for the youngest survivors vs. 2% of controls, 25% vs. 8% for 12- to 17-year-olds, and 28% vs. 12% for those 18 and older (P < .01 for all three comparisons).

Survivors were also significantly more likely to have any indicator of potential misuse (1.6% vs. 0.1%, 4.6% vs. 0.5%, and 7.4% vs. 1.2%, respectively, P < .001 for all) and both the youngest and oldest groups (but not 12- to 17-year-olds) were significantly more like to have opioid or substance use disorder (0.4% vs. 0% for 0-11 years, 5.76% vs. 4.2% for 18 years and older, P < .001 for both).

Among patients with any opioid prescription, survivors were significantly more likely than were controls of any age to have indicators for potential misuse. For example, 13% of survivors aged 18 years and older had prescriptions for high opioid doses, compared with 5% of controls, and 12% had prescription overlap, vs. 2%.

Compared with patients with leukemia, patients treated for bone malignancies had a 6% greater risk for having any indicator of misuse, while patients with other malignancies were at slightly lower risk for misuse than those who completed leukemia therapy.

Patients who received any stem cell transplant had an 8.4% greater risk for misuse compared with patients who had surgery only.
 

Opioids pre- and posttreatment?

“Being someone who takes care of a lot of bone cancer patients, I do see patients with these issues,” Dr. Spunt said.

Audience member Jack H. Staddon, MD, PhD, of the Billings (Montana) Clinic, noted the possibility that opioid use during treatment may have been carried on into the posttreatment period, and asked whether use of narcotics during treatment was an independent risk factor for posttreatment narcotic use or misuse.

The researchers plan to investigate this question in future studies, Dr. Ji replied.

They did not report a study funding source. Dr. Ji and coauthors and Dr. Staddon reported no relevant disclosures.

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.

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.

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.

Key clinical point: Allogeneic hematopoietic cell transplantation (allo-HCT) is an effective treatment strategy for patients with chronic-phase chronic myeloid leukemia (CML-CP) who are resistant or intolerant to prior tyrosine kinase inhibitors (TKIs). However, better patient selection and posttransplant strategies are needed to mitigate the risk of relapse.

Major finding: Pooled rates of overall survival, disease-free survival, complete remission, and molecular response in adult allo-HCT recipients were 84% (95% confidence interval [CI], 59%-99%), 66% (95% CI, 59%-73%), 56% (95% CI, 30%-80%), and 88% (95% CI, 62%-98%), respectively. Pooled rates of nonrelapse mortality and relapse were 20% (95% CI, 15%-26%) and 19% (95% CI, 10%-28%), respectively.

Study details: This was a systematic review and meta-analysis of 9 studies including 439 patients with TKI-resistant or intolerant CML-CP who received allo-HCT.

Disclosures: No funding source was identified. MA Moustafa reported consulting for Acrotech Biopharma and MA Kharfan-Dabaja reported consulting for Pharmacyclics and Daiichi Sankyo. Other authors declared no conflicts of interest.

Source: Yassine F et al. Hematol Oncol Stem Cell Ther. 2021 Mar 11. doi: 10.1016/j.hemonc.2021.02.003.

Key clinical point: Allogeneic hematopoietic cell transplantation (allo-HCT) is an effective treatment strategy for patients with chronic-phase chronic myeloid leukemia (CML-CP) who are resistant or intolerant to prior tyrosine kinase inhibitors (TKIs). However, better patient selection and posttransplant strategies are needed to mitigate the risk of relapse.

Major finding: Pooled rates of overall survival, disease-free survival, complete remission, and molecular response in adult allo-HCT recipients were 84% (95% confidence interval [CI], 59%-99%), 66% (95% CI, 59%-73%), 56% (95% CI, 30%-80%), and 88% (95% CI, 62%-98%), respectively. Pooled rates of nonrelapse mortality and relapse were 20% (95% CI, 15%-26%) and 19% (95% CI, 10%-28%), respectively.

Study details: This was a systematic review and meta-analysis of 9 studies including 439 patients with TKI-resistant or intolerant CML-CP who received allo-HCT.

Disclosures: No funding source was identified. MA Moustafa reported consulting for Acrotech Biopharma and MA Kharfan-Dabaja reported consulting for Pharmacyclics and Daiichi Sankyo. Other authors declared no conflicts of interest.

Source: Yassine F et al. Hematol Oncol Stem Cell Ther. 2021 Mar 11. doi: 10.1016/j.hemonc.2021.02.003.

Key clinical point: Allogeneic hematopoietic cell transplantation (allo-HCT) is an effective treatment strategy for patients with chronic-phase chronic myeloid leukemia (CML-CP) who are resistant or intolerant to prior tyrosine kinase inhibitors (TKIs). However, better patient selection and posttransplant strategies are needed to mitigate the risk of relapse.

Major finding: Pooled rates of overall survival, disease-free survival, complete remission, and molecular response in adult allo-HCT recipients were 84% (95% confidence interval [CI], 59%-99%), 66% (95% CI, 59%-73%), 56% (95% CI, 30%-80%), and 88% (95% CI, 62%-98%), respectively. Pooled rates of nonrelapse mortality and relapse were 20% (95% CI, 15%-26%) and 19% (95% CI, 10%-28%), respectively.

Study details: This was a systematic review and meta-analysis of 9 studies including 439 patients with TKI-resistant or intolerant CML-CP who received allo-HCT.

Disclosures: No funding source was identified. MA Moustafa reported consulting for Acrotech Biopharma and MA Kharfan-Dabaja reported consulting for Pharmacyclics and Daiichi Sankyo. Other authors declared no conflicts of interest.

Source: Yassine F et al. Hematol Oncol Stem Cell Ther. 2021 Mar 11. doi: 10.1016/j.hemonc.2021.02.003.

Key clinical point: Hyperfractionated cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, and dexamethasone (hyper-CVAD) plus dasatinib therapy has improved clinical outcomes in chronic myeloid leukemia in lymphoid blastic phase (CML-LBP) with survival comparable to that of Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL).

Major finding: Five-year overall (59% vs. 48%; P = .97) and progression-free (46% vs. 44%; P = .88) survival rates were similar in patients with CML-LBP and Ph-positive ALL.

Study details: This retrospective study included 23 and 62 patients with CML-LBP and newly diagnosed Ph-positive ALL, respectively, who were treated with hyper-CVAD plus dasatinib.

Disclosures: This work was supported in part by Cancer Center Support Grant to the University of Texas, MD Anderson. Some investigators reported honoraria, research grants, consulting fees, personal fees, patent and royalties, and membership on the board of directors or advisory committees from various pharmaceutical companies.

Source: Morita K et al. Cancer. 2021 Apr 6. doi: 10.1002/cncr.33539.

Key clinical point: Hyperfractionated cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, and dexamethasone (hyper-CVAD) plus dasatinib therapy has improved clinical outcomes in chronic myeloid leukemia in lymphoid blastic phase (CML-LBP) with survival comparable to that of Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL).

Major finding: Five-year overall (59% vs. 48%; P = .97) and progression-free (46% vs. 44%; P = .88) survival rates were similar in patients with CML-LBP and Ph-positive ALL.

Study details: This retrospective study included 23 and 62 patients with CML-LBP and newly diagnosed Ph-positive ALL, respectively, who were treated with hyper-CVAD plus dasatinib.

Disclosures: This work was supported in part by Cancer Center Support Grant to the University of Texas, MD Anderson. Some investigators reported honoraria, research grants, consulting fees, personal fees, patent and royalties, and membership on the board of directors or advisory committees from various pharmaceutical companies.

Source: Morita K et al. Cancer. 2021 Apr 6. doi: 10.1002/cncr.33539.

Key clinical point: Hyperfractionated cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, and dexamethasone (hyper-CVAD) plus dasatinib therapy has improved clinical outcomes in chronic myeloid leukemia in lymphoid blastic phase (CML-LBP) with survival comparable to that of Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL).

Major finding: Five-year overall (59% vs. 48%; P = .97) and progression-free (46% vs. 44%; P = .88) survival rates were similar in patients with CML-LBP and Ph-positive ALL.

Study details: This retrospective study included 23 and 62 patients with CML-LBP and newly diagnosed Ph-positive ALL, respectively, who were treated with hyper-CVAD plus dasatinib.

Disclosures: This work was supported in part by Cancer Center Support Grant to the University of Texas, MD Anderson. Some investigators reported honoraria, research grants, consulting fees, personal fees, patent and royalties, and membership on the board of directors or advisory committees from various pharmaceutical companies.

Source: Morita K et al. Cancer. 2021 Apr 6. doi: 10.1002/cncr.33539.

Key clinical point: Nilotinib treatment for chronic myeloid leukemia (CML) may be associated with arterial complications, particularly involving the carotid artery. These results urge for cardiovascular evaluation, with close vascular follow-up, in all patients initiating nilotinib.

Major finding: Arterial ultrasound anomalies were present in 25 patients, with the carotid bulb being the most involved territory (44%). Overall, vascular arterial anomaly was present in 33.8% of patients. Vascular adverse events were also present in 12.5% of patients with no cardiovascular risk factors.

Study details: This retrospective study evaluated 74 patients with CML treated with nilotinib at the Paoli-Calmettes Institute, Marseille, between 2006 and 2015.

Disclosures: No funding source was identified. The authors declared no conflicts of interest.

Source: Sarlon-Bartoli G et al. J Med Vasc. 2021 Mar 6. doi: 10.1016/j.jdmv.2021.02.002.

Key clinical point: Nilotinib treatment for chronic myeloid leukemia (CML) may be associated with arterial complications, particularly involving the carotid artery. These results urge for cardiovascular evaluation, with close vascular follow-up, in all patients initiating nilotinib.

Major finding: Arterial ultrasound anomalies were present in 25 patients, with the carotid bulb being the most involved territory (44%). Overall, vascular arterial anomaly was present in 33.8% of patients. Vascular adverse events were also present in 12.5% of patients with no cardiovascular risk factors.

Study details: This retrospective study evaluated 74 patients with CML treated with nilotinib at the Paoli-Calmettes Institute, Marseille, between 2006 and 2015.

Disclosures: No funding source was identified. The authors declared no conflicts of interest.

Source: Sarlon-Bartoli G et al. J Med Vasc. 2021 Mar 6. doi: 10.1016/j.jdmv.2021.02.002.

Key clinical point: Nilotinib treatment for chronic myeloid leukemia (CML) may be associated with arterial complications, particularly involving the carotid artery. These results urge for cardiovascular evaluation, with close vascular follow-up, in all patients initiating nilotinib.

Major finding: Arterial ultrasound anomalies were present in 25 patients, with the carotid bulb being the most involved territory (44%). Overall, vascular arterial anomaly was present in 33.8% of patients. Vascular adverse events were also present in 12.5% of patients with no cardiovascular risk factors.

Study details: This retrospective study evaluated 74 patients with CML treated with nilotinib at the Paoli-Calmettes Institute, Marseille, between 2006 and 2015.

Disclosures: No funding source was identified. The authors declared no conflicts of interest.

Source: Sarlon-Bartoli G et al. J Med Vasc. 2021 Mar 6. doi: 10.1016/j.jdmv.2021.02.002.

Key clinical point: With broader use of novel tyrosine kinase inhibitor (TKI) and a better understanding of the disease, the relative survival (RS) of patients with chronic myeloid leukemia (CML) in the United States has improved but is still not on par with the general population.

Major finding: Overall, rates of 5- and 10-year RS were 83.4% (95% confidence interval [CI], 81.6%-85.0%) and 72.8% (95% CI, 69.7%-75.6%), respectively. Ten-year RS was worse among patients aged 65 years or older vs. those aged less than 65 years. The 5-year RS for patients diagnosed between 2008-2014 and 2001-2007 was 87.0% and 81.0%, respectively (P less than .001).

Study details: Findings are from a US population-based study, including 3,946 patients diagnosed with BCR-ABL–positive CML during the period between the introduction of TKIs and the last available follow-up data (2001-2014).

Disclosures: No funding source was identified. The authors declared no conflicts of interest.

Source: Jamy O et al. Am J Hematol. 2021 Apr 17. doi: 10.1002/ajh.26195.

Key clinical point: With broader use of novel tyrosine kinase inhibitor (TKI) and a better understanding of the disease, the relative survival (RS) of patients with chronic myeloid leukemia (CML) in the United States has improved but is still not on par with the general population.

Major finding: Overall, rates of 5- and 10-year RS were 83.4% (95% confidence interval [CI], 81.6%-85.0%) and 72.8% (95% CI, 69.7%-75.6%), respectively. Ten-year RS was worse among patients aged 65 years or older vs. those aged less than 65 years. The 5-year RS for patients diagnosed between 2008-2014 and 2001-2007 was 87.0% and 81.0%, respectively (P less than .001).

Study details: Findings are from a US population-based study, including 3,946 patients diagnosed with BCR-ABL–positive CML during the period between the introduction of TKIs and the last available follow-up data (2001-2014).

Disclosures: No funding source was identified. The authors declared no conflicts of interest.

Source: Jamy O et al. Am J Hematol. 2021 Apr 17. doi: 10.1002/ajh.26195.

Key clinical point: With broader use of novel tyrosine kinase inhibitor (TKI) and a better understanding of the disease, the relative survival (RS) of patients with chronic myeloid leukemia (CML) in the United States has improved but is still not on par with the general population.

Major finding: Overall, rates of 5- and 10-year RS were 83.4% (95% confidence interval [CI], 81.6%-85.0%) and 72.8% (95% CI, 69.7%-75.6%), respectively. Ten-year RS was worse among patients aged 65 years or older vs. those aged less than 65 years. The 5-year RS for patients diagnosed between 2008-2014 and 2001-2007 was 87.0% and 81.0%, respectively (P less than .001).

Study details: Findings are from a US population-based study, including 3,946 patients diagnosed with BCR-ABL–positive CML during the period between the introduction of TKIs and the last available follow-up data (2001-2014).

Disclosures: No funding source was identified. The authors declared no conflicts of interest.

Source: Jamy O et al. Am J Hematol. 2021 Apr 17. doi: 10.1002/ajh.26195.

Key clinical point: Gastrointestinal adverse event (AE) profiles differed significantly among different tyrosine kinase inhibitors (TKIs) and should be considered for optimal therapy selection for patients with chronic-phase chronic myeloid leukemia (CML-CP).

Major finding: The mean incidence of all gastrointestinal AEs was highest with bosutinib (52.9%), followed by imatinib (24.2%), dasatinib (20.4%), and nilotinib (9.1%). The incidence of most gastrointestinal AEs was consistently and significantly higher for bosutinib and lower for nilotinib vs. other TKIs (P less than .0016). Overall survival rates over 12 months were more than 90% for all TKIs.

Study details: Meta-analysis of 43 peer-reviewed studies including a heterogeneous population of 10,789 patients with CML with varying disease stages.

Disclosures: This study was funded by Georgia Institute of Technology President’s Undergraduate Research Award, a grant from Incyte pharmaceuticals, Children’s Hospital of Atlanta Aflac pilot grant, and National Science Foundation CAREER award. V Kota reported honoraria for consultancy from Novartis and Pfizer. Other authors declared no conflicts of interest.

Source: Mohanavelu P et al. Cancers. 2021 Apr 1. doi: 10.3390/cancers13071643.

Key clinical point: Gastrointestinal adverse event (AE) profiles differed significantly among different tyrosine kinase inhibitors (TKIs) and should be considered for optimal therapy selection for patients with chronic-phase chronic myeloid leukemia (CML-CP).

Major finding: The mean incidence of all gastrointestinal AEs was highest with bosutinib (52.9%), followed by imatinib (24.2%), dasatinib (20.4%), and nilotinib (9.1%). The incidence of most gastrointestinal AEs was consistently and significantly higher for bosutinib and lower for nilotinib vs. other TKIs (P less than .0016). Overall survival rates over 12 months were more than 90% for all TKIs.

Study details: Meta-analysis of 43 peer-reviewed studies including a heterogeneous population of 10,789 patients with CML with varying disease stages.

Disclosures: This study was funded by Georgia Institute of Technology President’s Undergraduate Research Award, a grant from Incyte pharmaceuticals, Children’s Hospital of Atlanta Aflac pilot grant, and National Science Foundation CAREER award. V Kota reported honoraria for consultancy from Novartis and Pfizer. Other authors declared no conflicts of interest.

Source: Mohanavelu P et al. Cancers. 2021 Apr 1. doi: 10.3390/cancers13071643.

Key clinical point: Gastrointestinal adverse event (AE) profiles differed significantly among different tyrosine kinase inhibitors (TKIs) and should be considered for optimal therapy selection for patients with chronic-phase chronic myeloid leukemia (CML-CP).

Major finding: The mean incidence of all gastrointestinal AEs was highest with bosutinib (52.9%), followed by imatinib (24.2%), dasatinib (20.4%), and nilotinib (9.1%). The incidence of most gastrointestinal AEs was consistently and significantly higher for bosutinib and lower for nilotinib vs. other TKIs (P less than .0016). Overall survival rates over 12 months were more than 90% for all TKIs.

Study details: Meta-analysis of 43 peer-reviewed studies including a heterogeneous population of 10,789 patients with CML with varying disease stages.

Disclosures: This study was funded by Georgia Institute of Technology President’s Undergraduate Research Award, a grant from Incyte pharmaceuticals, Children’s Hospital of Atlanta Aflac pilot grant, and National Science Foundation CAREER award. V Kota reported honoraria for consultancy from Novartis and Pfizer. Other authors declared no conflicts of interest.

Source: Mohanavelu P et al. Cancers. 2021 Apr 1. doi: 10.3390/cancers13071643.