Clinical Edge Journal Scan

Key clinical point: In patients with advanced pancreatic cancer, pancreatic enzyme replacement therapy (PERT) for exocrine pancreatic insufficiency (EPI) does not affect survival.

Major finding: There was no significant difference in the overall survival in patients who received PERT vs. those who did not (weighted estimate, 9.5 months vs. 8.1 months; P = .464). No PERT-related adverse events were reported.

Study details: A meta-analysis of 4 randomized controlled trials including 194 patients with pancreatic cancer. The patients with EPI received PERT.

Disclosures: No specific sponsor was identified. One reviewer received personal fees from Abbott Pharmaceuticals and Mylan.

Citation: Ammar K. Expert Rev Gastroenterol Hepatol. 2021 Feb 15. doi: 10.1080/17474124.2021.1884544.

Key clinical point: In patients with advanced pancreatic cancer, pancreatic enzyme replacement therapy (PERT) for exocrine pancreatic insufficiency (EPI) does not affect survival.

Major finding: There was no significant difference in the overall survival in patients who received PERT vs. those who did not (weighted estimate, 9.5 months vs. 8.1 months; P = .464). No PERT-related adverse events were reported.

Study details: A meta-analysis of 4 randomized controlled trials including 194 patients with pancreatic cancer. The patients with EPI received PERT.

Disclosures: No specific sponsor was identified. One reviewer received personal fees from Abbott Pharmaceuticals and Mylan.

Citation: Ammar K. Expert Rev Gastroenterol Hepatol. 2021 Feb 15. doi: 10.1080/17474124.2021.1884544.

Key clinical point: In patients with advanced pancreatic cancer, pancreatic enzyme replacement therapy (PERT) for exocrine pancreatic insufficiency (EPI) does not affect survival.

Major finding: There was no significant difference in the overall survival in patients who received PERT vs. those who did not (weighted estimate, 9.5 months vs. 8.1 months; P = .464). No PERT-related adverse events were reported.

Study details: A meta-analysis of 4 randomized controlled trials including 194 patients with pancreatic cancer. The patients with EPI received PERT.

Disclosures: No specific sponsor was identified. One reviewer received personal fees from Abbott Pharmaceuticals and Mylan.

Citation: Ammar K. Expert Rev Gastroenterol Hepatol. 2021 Feb 15. doi: 10.1080/17474124.2021.1884544.

Key clinical point: Presence of exocrine pancreatic insufficiency (EPI) in patients with cystic fibrosis is associated with lower levels of phytosterol and cholesterol. Pancreatic enzyme supplement improves cholesterol levels in these patients.

Major finding: Total fat and cholesterol intake were higher in patients with cystic fibrosis. Total cholesterol, low-density lipoprotein cholesterol, campesterol, and β-sitosterol levels were significantly lower in cystic fibrosis patients with EPI vs. those without (all P less than .05). The rate of hypocholesterolemia was lower in patients with EPI receiving a supplementation dose of greater than 2500 U of lipase/g of fat (P = .0026).

Study details: The study included 55 patients with cystic fibrosis and 45 healthy adults. Forty-eight patients with cystic fibrosis had EPI (fecal elastase-1 concentrations less than 100 µg/g) and received pancreatic enzymes.

Disclosures: The study was supported by the Polish National Science Centre. The authors declared no conflicts of interest.

Citation: Drzymała-Czyż S et al. Biomolecules. 2021 Feb 19. doi: 10.3390/biom11020313.

Key clinical point: Presence of exocrine pancreatic insufficiency (EPI) in patients with cystic fibrosis is associated with lower levels of phytosterol and cholesterol. Pancreatic enzyme supplement improves cholesterol levels in these patients.

Major finding: Total fat and cholesterol intake were higher in patients with cystic fibrosis. Total cholesterol, low-density lipoprotein cholesterol, campesterol, and β-sitosterol levels were significantly lower in cystic fibrosis patients with EPI vs. those without (all P less than .05). The rate of hypocholesterolemia was lower in patients with EPI receiving a supplementation dose of greater than 2500 U of lipase/g of fat (P = .0026).

Study details: The study included 55 patients with cystic fibrosis and 45 healthy adults. Forty-eight patients with cystic fibrosis had EPI (fecal elastase-1 concentrations less than 100 µg/g) and received pancreatic enzymes.

Disclosures: The study was supported by the Polish National Science Centre. The authors declared no conflicts of interest.

Citation: Drzymała-Czyż S et al. Biomolecules. 2021 Feb 19. doi: 10.3390/biom11020313.

Key clinical point: Presence of exocrine pancreatic insufficiency (EPI) in patients with cystic fibrosis is associated with lower levels of phytosterol and cholesterol. Pancreatic enzyme supplement improves cholesterol levels in these patients.

Major finding: Total fat and cholesterol intake were higher in patients with cystic fibrosis. Total cholesterol, low-density lipoprotein cholesterol, campesterol, and β-sitosterol levels were significantly lower in cystic fibrosis patients with EPI vs. those without (all P less than .05). The rate of hypocholesterolemia was lower in patients with EPI receiving a supplementation dose of greater than 2500 U of lipase/g of fat (P = .0026).

Study details: The study included 55 patients with cystic fibrosis and 45 healthy adults. Forty-eight patients with cystic fibrosis had EPI (fecal elastase-1 concentrations less than 100 µg/g) and received pancreatic enzymes.

Disclosures: The study was supported by the Polish National Science Centre. The authors declared no conflicts of interest.

Citation: Drzymała-Czyż S et al. Biomolecules. 2021 Feb 19. doi: 10.3390/biom11020313.

Key clinical point: Impaired exocrine pancreatic function is reported in a subgroup of patients undergoing esophagectomy, and pancreatic enzyme replacement therapy can improve symptoms and body weight in these patients.

Major finding: Fecal elastase-1 levels of less than 200 µg/g were reported in 16%-18% of patients at 4-6 months following esophagectomy. Pancreatic enzyme replacement therapy (25,000-50,000 units lipase per meal) improved gastrointestinal symptoms, body weight, and normalized stool in patients with steatorrhea.

Study details: Systematic review of 3 prospective cohort studies reporting exocrine pancreatic insufficiency (EPI) in 107 patients undergoing esophagectomy.

Disclosures: No sponsor was identified for this review.

Citation: Blonk L et al. Dis Esophagus. 2021 Feb 9. doi: 10.1093/dote/doab003.

Key clinical point: Impaired exocrine pancreatic function is reported in a subgroup of patients undergoing esophagectomy, and pancreatic enzyme replacement therapy can improve symptoms and body weight in these patients.

Major finding: Fecal elastase-1 levels of less than 200 µg/g were reported in 16%-18% of patients at 4-6 months following esophagectomy. Pancreatic enzyme replacement therapy (25,000-50,000 units lipase per meal) improved gastrointestinal symptoms, body weight, and normalized stool in patients with steatorrhea.

Study details: Systematic review of 3 prospective cohort studies reporting exocrine pancreatic insufficiency (EPI) in 107 patients undergoing esophagectomy.

Disclosures: No sponsor was identified for this review.

Citation: Blonk L et al. Dis Esophagus. 2021 Feb 9. doi: 10.1093/dote/doab003.

Key clinical point: Impaired exocrine pancreatic function is reported in a subgroup of patients undergoing esophagectomy, and pancreatic enzyme replacement therapy can improve symptoms and body weight in these patients.

Major finding: Fecal elastase-1 levels of less than 200 µg/g were reported in 16%-18% of patients at 4-6 months following esophagectomy. Pancreatic enzyme replacement therapy (25,000-50,000 units lipase per meal) improved gastrointestinal symptoms, body weight, and normalized stool in patients with steatorrhea.

Study details: Systematic review of 3 prospective cohort studies reporting exocrine pancreatic insufficiency (EPI) in 107 patients undergoing esophagectomy.

Disclosures: No sponsor was identified for this review.

Citation: Blonk L et al. Dis Esophagus. 2021 Feb 9. doi: 10.1093/dote/doab003.

Key clinical point: Asymptomatic patients with pancreatic trauma may have exocrine insufficiency when evaluated with specific investigations.

Major finding: Patients who underwent pancreatic resection had a lower fecal elastase value vs. those who did not, but the difference was not statistically significant (113 vs. 162.5 μg/g; P = .7). One patient in the resection group reported steatorrhea. Three patients in the pancreatic resection and 1 in the nonresection group had severe pancreatic exocrine insufficiency (P = .7). No patient required pancreatic enzyme supplements.

Study details: A study of 20 patients (mean age, 25 years) with pancreatic trauma between June 2016 and December 2017. Partial pancreatic resection was performed in 12 patients. Exocrine functions were evaluated with the fecal elastase test at 6 months.

Disclosures: No study sponsor was identified.

Citation: Colney L et al. Eur J Trauma Emerg Surg. 2021 Mar 14. doi: 10.1007/s00068-021-01638-8.

Key clinical point: Asymptomatic patients with pancreatic trauma may have exocrine insufficiency when evaluated with specific investigations.

Major finding: Patients who underwent pancreatic resection had a lower fecal elastase value vs. those who did not, but the difference was not statistically significant (113 vs. 162.5 μg/g; P = .7). One patient in the resection group reported steatorrhea. Three patients in the pancreatic resection and 1 in the nonresection group had severe pancreatic exocrine insufficiency (P = .7). No patient required pancreatic enzyme supplements.

Study details: A study of 20 patients (mean age, 25 years) with pancreatic trauma between June 2016 and December 2017. Partial pancreatic resection was performed in 12 patients. Exocrine functions were evaluated with the fecal elastase test at 6 months.

Disclosures: No study sponsor was identified.

Citation: Colney L et al. Eur J Trauma Emerg Surg. 2021 Mar 14. doi: 10.1007/s00068-021-01638-8.

Key clinical point: Asymptomatic patients with pancreatic trauma may have exocrine insufficiency when evaluated with specific investigations.

Major finding: Patients who underwent pancreatic resection had a lower fecal elastase value vs. those who did not, but the difference was not statistically significant (113 vs. 162.5 μg/g; P = .7). One patient in the resection group reported steatorrhea. Three patients in the pancreatic resection and 1 in the nonresection group had severe pancreatic exocrine insufficiency (P = .7). No patient required pancreatic enzyme supplements.

Study details: A study of 20 patients (mean age, 25 years) with pancreatic trauma between June 2016 and December 2017. Partial pancreatic resection was performed in 12 patients. Exocrine functions were evaluated with the fecal elastase test at 6 months.

Disclosures: No study sponsor was identified.

Citation: Colney L et al. Eur J Trauma Emerg Surg. 2021 Mar 14. doi: 10.1007/s00068-021-01638-8.

Key clinical point: Patients who experience malabsorption with sorafenib treatment may develop exocrine pancreatic insufficiency (EPI); supplementation with pancreatic enzymes may benefit these patients.

Major finding: Two patients had moderate and 6 patients had severe pancreatic insufficiency. Six patients who developed EPI received pancreatic enzymes and recovered from the malabsorption symptoms within 1 month. The fecal elastase values recovered in 5 of 6 patients who received pancreatic enzymes.

Study details: A prospective study of 21 patients with hepatocellular carcinoma treated with sorafenib who developed malabsorption.

Disclosures: No study sponsor was identified. The authors received speaker fees and grants outside the study work.

Citation: Díaz-González A et al. J Clin Gastroenterol. 2021 Mar 1. doi: 10.1097/MCG.0000000000001366.

Key clinical point: Patients who experience malabsorption with sorafenib treatment may develop exocrine pancreatic insufficiency (EPI); supplementation with pancreatic enzymes may benefit these patients.

Major finding: Two patients had moderate and 6 patients had severe pancreatic insufficiency. Six patients who developed EPI received pancreatic enzymes and recovered from the malabsorption symptoms within 1 month. The fecal elastase values recovered in 5 of 6 patients who received pancreatic enzymes.

Study details: A prospective study of 21 patients with hepatocellular carcinoma treated with sorafenib who developed malabsorption.

Disclosures: No study sponsor was identified. The authors received speaker fees and grants outside the study work.

Citation: Díaz-González A et al. J Clin Gastroenterol. 2021 Mar 1. doi: 10.1097/MCG.0000000000001366.

Key clinical point: Patients who experience malabsorption with sorafenib treatment may develop exocrine pancreatic insufficiency (EPI); supplementation with pancreatic enzymes may benefit these patients.

Major finding: Two patients had moderate and 6 patients had severe pancreatic insufficiency. Six patients who developed EPI received pancreatic enzymes and recovered from the malabsorption symptoms within 1 month. The fecal elastase values recovered in 5 of 6 patients who received pancreatic enzymes.

Study details: A prospective study of 21 patients with hepatocellular carcinoma treated with sorafenib who developed malabsorption.

Disclosures: No study sponsor was identified. The authors received speaker fees and grants outside the study work.

Citation: Díaz-González A et al. J Clin Gastroenterol. 2021 Mar 1. doi: 10.1097/MCG.0000000000001366.

Key clinical point: Exocrine pancreatic insufficiency is a feature of type 1 diabetes (T1D). Lower levels of fecal elastase-1 and amylase are reported in patients with T1D vs. healthy individuals.

Major finding: Compared with healthy individuals, fecal elastase-1 levels were significantly lower in participants with new-onset and long-standing T1D (P = .0070 and .0010, respectively). Pancreatic amylase levels were significantly lower in patients with long-standing T1D vs. healthy individuals (P = .0001). The markers of impaired exocrine function tests (fecal elastase-1, serum pancreatic amylase, and lipase) correlated with the reduction of fasting and urinary C-peptide (all P less than .001).

Study details: A single-center, cross-sectional study of pancreatic exocrine function in adult patients with new-onset T1D (n = 12) or long-standing T1D (n = 19) and healthy individuals (n = 25).

Disclosures: This study was supported by a grant received by Battaglia M from the Italian Diabetes Society (SID) Research Foundation SID.

Citation: Dozio N et al. BMJ Open Diab Res Care. 2021 Feb. doi: 10.1136/bmjdrc-2019-001158.

Key clinical point: Exocrine pancreatic insufficiency is a feature of type 1 diabetes (T1D). Lower levels of fecal elastase-1 and amylase are reported in patients with T1D vs. healthy individuals.

Major finding: Compared with healthy individuals, fecal elastase-1 levels were significantly lower in participants with new-onset and long-standing T1D (P = .0070 and .0010, respectively). Pancreatic amylase levels were significantly lower in patients with long-standing T1D vs. healthy individuals (P = .0001). The markers of impaired exocrine function tests (fecal elastase-1, serum pancreatic amylase, and lipase) correlated with the reduction of fasting and urinary C-peptide (all P less than .001).

Study details: A single-center, cross-sectional study of pancreatic exocrine function in adult patients with new-onset T1D (n = 12) or long-standing T1D (n = 19) and healthy individuals (n = 25).

Disclosures: This study was supported by a grant received by Battaglia M from the Italian Diabetes Society (SID) Research Foundation SID.

Citation: Dozio N et al. BMJ Open Diab Res Care. 2021 Feb. doi: 10.1136/bmjdrc-2019-001158.

Key clinical point: Exocrine pancreatic insufficiency is a feature of type 1 diabetes (T1D). Lower levels of fecal elastase-1 and amylase are reported in patients with T1D vs. healthy individuals.

Major finding: Compared with healthy individuals, fecal elastase-1 levels were significantly lower in participants with new-onset and long-standing T1D (P = .0070 and .0010, respectively). Pancreatic amylase levels were significantly lower in patients with long-standing T1D vs. healthy individuals (P = .0001). The markers of impaired exocrine function tests (fecal elastase-1, serum pancreatic amylase, and lipase) correlated with the reduction of fasting and urinary C-peptide (all P less than .001).

Study details: A single-center, cross-sectional study of pancreatic exocrine function in adult patients with new-onset T1D (n = 12) or long-standing T1D (n = 19) and healthy individuals (n = 25).

Disclosures: This study was supported by a grant received by Battaglia M from the Italian Diabetes Society (SID) Research Foundation SID.

Citation: Dozio N et al. BMJ Open Diab Res Care. 2021 Feb. doi: 10.1136/bmjdrc-2019-001158.

Key clinical point: Exocrine pancreatic insufficiency (EPI) is common in patients with gastroenteropancreatic neuroendocrine neoplasia (NEN) receiving somatostatin analogs. Pancreatic enzyme replacement therapy (PERT) is justified in patients experiencing EPI symptoms.

Major findings: Studies have reported an EPI prevalence of 20% to 38% in patients with NEN receiving somatostatin analogs. Its symptoms overlap with clinical features of tumor and common side effects of somatostatin analogs. EPI can be diagnosed with noninvasive fecal elastase-1 test and is easy to treat using PERT. However, there is a general lack of awareness about EPI and PERT. A multidisciplinary team of gastroenterologists and nutritionists can increase the odds of providing the best care.

Study details: An editorial on EPI in patients with NEN receiving somatostatin analogs.

Disclosures: No specific funding was identified for this editorial. Panzuto F received speaker honoraria from Mylan Italia.

Source: Panzuto F et al. Expert Opin Drug Saf. 2021 Feb 2. doi: 10.1080/14740338.2021.1881478.

Key clinical point: Exocrine pancreatic insufficiency (EPI) is common in patients with gastroenteropancreatic neuroendocrine neoplasia (NEN) receiving somatostatin analogs. Pancreatic enzyme replacement therapy (PERT) is justified in patients experiencing EPI symptoms.

Major findings: Studies have reported an EPI prevalence of 20% to 38% in patients with NEN receiving somatostatin analogs. Its symptoms overlap with clinical features of tumor and common side effects of somatostatin analogs. EPI can be diagnosed with noninvasive fecal elastase-1 test and is easy to treat using PERT. However, there is a general lack of awareness about EPI and PERT. A multidisciplinary team of gastroenterologists and nutritionists can increase the odds of providing the best care.

Study details: An editorial on EPI in patients with NEN receiving somatostatin analogs.

Disclosures: No specific funding was identified for this editorial. Panzuto F received speaker honoraria from Mylan Italia.

Source: Panzuto F et al. Expert Opin Drug Saf. 2021 Feb 2. doi: 10.1080/14740338.2021.1881478.

Key clinical point: Exocrine pancreatic insufficiency (EPI) is common in patients with gastroenteropancreatic neuroendocrine neoplasia (NEN) receiving somatostatin analogs. Pancreatic enzyme replacement therapy (PERT) is justified in patients experiencing EPI symptoms.

Major findings: Studies have reported an EPI prevalence of 20% to 38% in patients with NEN receiving somatostatin analogs. Its symptoms overlap with clinical features of tumor and common side effects of somatostatin analogs. EPI can be diagnosed with noninvasive fecal elastase-1 test and is easy to treat using PERT. However, there is a general lack of awareness about EPI and PERT. A multidisciplinary team of gastroenterologists and nutritionists can increase the odds of providing the best care.

Study details: An editorial on EPI in patients with NEN receiving somatostatin analogs.

Disclosures: No specific funding was identified for this editorial. Panzuto F received speaker honoraria from Mylan Italia.

Source: Panzuto F et al. Expert Opin Drug Saf. 2021 Feb 2. doi: 10.1080/14740338.2021.1881478.

Key clinical point: Pancrelipase improves stool consistency and frequency and coefficient of fat absorption (CFA) in patients with chronic pancreatitis with moderate to severe exocrine pancreatic insufficiency (EPI).

Major finding: Higher number of patients reported decreased stool frequency at week 1 with pancrelipase vs. placebo (72% vs. 38%; P less than .001). Mean change in CFA from baseline was significantly greater with pancrelipase vs. placebo (24.7% vs. 6.4%; P less than .001). Improvements in stool consistency (P = .03) and frequency (P less than .001) correlated with CFA improvement. Symptom improvements persisted over 52 weeks of treatment.

Study details: A pooled study of 2 randomized double-blind trials including patients with chronic pancreatitis and EPI, who received either pancrelipase (n = 59) or placebo (n = 57). Thirty-four patients received open-label pancrelipase treatment for 51 weeks in another trial.

Disclosures: The editorial support for this study was funded by AbbVie. The authors reported no conflicts of interest.

Source: Barkin JA et al. Pancreas. 2021 Feb 1. doi: 10.1097/MPA.0000000000001733.

Key clinical point: Pancrelipase improves stool consistency and frequency and coefficient of fat absorption (CFA) in patients with chronic pancreatitis with moderate to severe exocrine pancreatic insufficiency (EPI).

Major finding: Higher number of patients reported decreased stool frequency at week 1 with pancrelipase vs. placebo (72% vs. 38%; P less than .001). Mean change in CFA from baseline was significantly greater with pancrelipase vs. placebo (24.7% vs. 6.4%; P less than .001). Improvements in stool consistency (P = .03) and frequency (P less than .001) correlated with CFA improvement. Symptom improvements persisted over 52 weeks of treatment.

Study details: A pooled study of 2 randomized double-blind trials including patients with chronic pancreatitis and EPI, who received either pancrelipase (n = 59) or placebo (n = 57). Thirty-four patients received open-label pancrelipase treatment for 51 weeks in another trial.

Disclosures: The editorial support for this study was funded by AbbVie. The authors reported no conflicts of interest.

Source: Barkin JA et al. Pancreas. 2021 Feb 1. doi: 10.1097/MPA.0000000000001733.

Key clinical point: Pancrelipase improves stool consistency and frequency and coefficient of fat absorption (CFA) in patients with chronic pancreatitis with moderate to severe exocrine pancreatic insufficiency (EPI).

Major finding: Higher number of patients reported decreased stool frequency at week 1 with pancrelipase vs. placebo (72% vs. 38%; P less than .001). Mean change in CFA from baseline was significantly greater with pancrelipase vs. placebo (24.7% vs. 6.4%; P less than .001). Improvements in stool consistency (P = .03) and frequency (P less than .001) correlated with CFA improvement. Symptom improvements persisted over 52 weeks of treatment.

Study details: A pooled study of 2 randomized double-blind trials including patients with chronic pancreatitis and EPI, who received either pancrelipase (n = 59) or placebo (n = 57). Thirty-four patients received open-label pancrelipase treatment for 51 weeks in another trial.

Disclosures: The editorial support for this study was funded by AbbVie. The authors reported no conflicts of interest.

Source: Barkin JA et al. Pancreas. 2021 Feb 1. doi: 10.1097/MPA.0000000000001733.

Although TFR is a reality on today's management of CML patients, it is important to emphasize a proper molecular monitoring after TKI discontinuation following the current NCCN and ELN guidelines. However, late relapses may occur after one year of therapy, although there are uncommon. In a recent letter to the editor in the journal Leukemia, investigators that participated in the EURO-SKI trial planned to follow patients beyond the 3 years scheduled in the trial and they reported the outcomes in what they called the AFTER-SKI trial. With a follow-up of 72 months, 12 out of 111 patients (10.8%) who were in TFR at 36 months, subsequently lost MMR. What is interesting is that the molecular status at 36 months appears highly predictive of later relapse, as only 1 patient out of 98 in MR4 at month 36 lost MMR in the following 3 years. Conversely, 11 of the 13 patients not in MR4 at month 36 lost MMR during follow-up.

For older CML patients not eligible for TFR or after TFR failure, long term therapy with TKI is the only option. However, we know that many patients can suffer from chronic AEs that will impact long term quality of life. A recent publication of the Italian phase III multicentric randomized OPTkIMA study aimed to evaluate if a progressive de‐escalation of TKIs was able to maintain the molecular response (MR^3.0) and improve Health Related Quality of Life (HRQoL). 166 elderly CML patients in stable MR^3.0/MR^4.0completed the first year of any TKI intermittent schedule, 1 month ON and 1 month OFF. The first-year probability of maintaining the MR^3.0 was 81%. No patients progressed to accelerated/blastic phase. All patients who lost the molecular response regained the MR^3.0 after resuming TKI continuously, and none suffered from TKI withdrawn syndrome. However, data related with quality of life was confounded by several factors and non-conclusive, for which longer follow up will be needed.
 

Although TFR is a reality on today's management of CML patients, it is important to emphasize a proper molecular monitoring after TKI discontinuation following the current NCCN and ELN guidelines. However, late relapses may occur after one year of therapy, although there are uncommon. In a recent letter to the editor in the journal Leukemia, investigators that participated in the EURO-SKI trial planned to follow patients beyond the 3 years scheduled in the trial and they reported the outcomes in what they called the AFTER-SKI trial. With a follow-up of 72 months, 12 out of 111 patients (10.8%) who were in TFR at 36 months, subsequently lost MMR. What is interesting is that the molecular status at 36 months appears highly predictive of later relapse, as only 1 patient out of 98 in MR4 at month 36 lost MMR in the following 3 years. Conversely, 11 of the 13 patients not in MR4 at month 36 lost MMR during follow-up.

For older CML patients not eligible for TFR or after TFR failure, long term therapy with TKI is the only option. However, we know that many patients can suffer from chronic AEs that will impact long term quality of life. A recent publication of the Italian phase III multicentric randomized OPTkIMA study aimed to evaluate if a progressive de‐escalation of TKIs was able to maintain the molecular response (MR^3.0) and improve Health Related Quality of Life (HRQoL). 166 elderly CML patients in stable MR^3.0/MR^4.0completed the first year of any TKI intermittent schedule, 1 month ON and 1 month OFF. The first-year probability of maintaining the MR^3.0 was 81%. No patients progressed to accelerated/blastic phase. All patients who lost the molecular response regained the MR^3.0 after resuming TKI continuously, and none suffered from TKI withdrawn syndrome. However, data related with quality of life was confounded by several factors and non-conclusive, for which longer follow up will be needed.
 

Although TFR is a reality on today's management of CML patients, it is important to emphasize a proper molecular monitoring after TKI discontinuation following the current NCCN and ELN guidelines. However, late relapses may occur after one year of therapy, although there are uncommon. In a recent letter to the editor in the journal Leukemia, investigators that participated in the EURO-SKI trial planned to follow patients beyond the 3 years scheduled in the trial and they reported the outcomes in what they called the AFTER-SKI trial. With a follow-up of 72 months, 12 out of 111 patients (10.8%) who were in TFR at 36 months, subsequently lost MMR. What is interesting is that the molecular status at 36 months appears highly predictive of later relapse, as only 1 patient out of 98 in MR4 at month 36 lost MMR in the following 3 years. Conversely, 11 of the 13 patients not in MR4 at month 36 lost MMR during follow-up.

For older CML patients not eligible for TFR or after TFR failure, long term therapy with TKI is the only option. However, we know that many patients can suffer from chronic AEs that will impact long term quality of life. A recent publication of the Italian phase III multicentric randomized OPTkIMA study aimed to evaluate if a progressive de‐escalation of TKIs was able to maintain the molecular response (MR^3.0) and improve Health Related Quality of Life (HRQoL). 166 elderly CML patients in stable MR^3.0/MR^4.0completed the first year of any TKI intermittent schedule, 1 month ON and 1 month OFF. The first-year probability of maintaining the MR^3.0 was 81%. No patients progressed to accelerated/blastic phase. All patients who lost the molecular response regained the MR^3.0 after resuming TKI continuously, and none suffered from TKI withdrawn syndrome. However, data related with quality of life was confounded by several factors and non-conclusive, for which longer follow up will be needed.
 

Key clinical point: G2677T/A and C3435T polymorphisms of multidrug resistance protein 1 (MDR1) play a role in response to imatinib mesylate (IM) in Caucasian population with chronic myeloid leukemia (CML).

Major finding: Variant T/A of G2677 marked responsiveness to IM therapy in Caucasian population under the recessive model (odds ratio [OR], 1.43; P = .01). The 3435TT genotype was significantly associated with increased resistance to IM therapy mainly in Caucasian population under dominant (OR, 1.49; P = .03) and heterozygous (OR, 1.52; P = .04) models.

Study details: Findings are from a meta-analysis of 17 studies involving 4,494 patients with CML; majority were in chronic phase.

Disclosures: The authors did not receive any financial support for research, authorship, and/or publication of this article. The authors declared no potential conflicts of interest.

Source: Louati N et al. J Oncol Pharm Pract. 2021 Feb 10. doi: 10.1177/1078155220981150.

Key clinical point: G2677T/A and C3435T polymorphisms of multidrug resistance protein 1 (MDR1) play a role in response to imatinib mesylate (IM) in Caucasian population with chronic myeloid leukemia (CML).

Major finding: Variant T/A of G2677 marked responsiveness to IM therapy in Caucasian population under the recessive model (odds ratio [OR], 1.43; P = .01). The 3435TT genotype was significantly associated with increased resistance to IM therapy mainly in Caucasian population under dominant (OR, 1.49; P = .03) and heterozygous (OR, 1.52; P = .04) models.

Study details: Findings are from a meta-analysis of 17 studies involving 4,494 patients with CML; majority were in chronic phase.

Disclosures: The authors did not receive any financial support for research, authorship, and/or publication of this article. The authors declared no potential conflicts of interest.

Source: Louati N et al. J Oncol Pharm Pract. 2021 Feb 10. doi: 10.1177/1078155220981150.

Key clinical point: G2677T/A and C3435T polymorphisms of multidrug resistance protein 1 (MDR1) play a role in response to imatinib mesylate (IM) in Caucasian population with chronic myeloid leukemia (CML).

Major finding: Variant T/A of G2677 marked responsiveness to IM therapy in Caucasian population under the recessive model (odds ratio [OR], 1.43; P = .01). The 3435TT genotype was significantly associated with increased resistance to IM therapy mainly in Caucasian population under dominant (OR, 1.49; P = .03) and heterozygous (OR, 1.52; P = .04) models.

Study details: Findings are from a meta-analysis of 17 studies involving 4,494 patients with CML; majority were in chronic phase.

Disclosures: The authors did not receive any financial support for research, authorship, and/or publication of this article. The authors declared no potential conflicts of interest.

Source: Louati N et al. J Oncol Pharm Pract. 2021 Feb 10. doi: 10.1177/1078155220981150.