Myelodysplastic Syndrome

The current COVID-19 pandemic has afflicted over 44 million individuals across the planet and been responsible for over 1 million deaths, particularly in high-risk populations. As a result of the overall advanced age, frailty and pre-existing comorbidities of patients with MDS, SARS-Cov2 was feared to be particularly dangerous in this patient population. A recent study by Mossuto et al describes the outcomes of patients with MDS with SARS-CoV-2 infection during the Coronavirus outbreak in Italy. Among a total of 5326 patients with MDS followed during the study period, 63 (1.18%) had confirmed SARS-CoV-2 infection. With a median age of 73 years, the mortality rate among these patients was 52% compared to that of the non-MDS population (24%), and was particularly high on male MDS patients (73% of total deaths). Respiratory failure was the cause of death in all the MDS patients with ARDS in 50% of deceased patients, and with majority of patients who were able to recover having lower risk IPSS-R categories. Interestingly, no differences in mortality or severity of infection were observed based on the type of therapy received for their MDS. These findings are not surprising given the underlying inflammation and immunosuppression in patients with MDS. Until the development of COVID-19 vaccines has been completed, identification of high-risk populations and specific guidelines for the management of SARS-CoV-2 infection in patients with MDS remains of paramount importance.

Clonal hematopoiesis is a known cardiovascular risk factor which has been associated with increased risk of cardiac and cerebrovascular events. Recent studies have also associated MDS with higher than expected cardiovascular comorbidities and cardiovascular-related deaths. In accordance to prior publications by Naqvi et al, a recent study by Faber et al retrospectively evaluated 236 MDS patients and studied the associations of somatic mutations with cardiovascular risk. Overall, the authors observed that 27% of patients in their study population developed vascular event, and that ASXL1 mutations were predictive of vascular disease by multivariate analysis (with an odds ratio of 4.2). This data further supports the biological connection between comorbidities and hematopoietic clonal disorders, the role of inflammaging and the need to maximize cardiovascular risk factor care in patients with MDS and develop specific therapies targeting both the disease biology and the underlying mechanisms leading to increased cardiovascular risk.

Guillermo Montalban Bravo, MD
Assistant Professor, Department of Leukemia, Division of Cancer Medicine
MD Anderson Cancer Center, Houston, TX

The current COVID-19 pandemic has afflicted over 44 million individuals across the planet and been responsible for over 1 million deaths, particularly in high-risk populations. As a result of the overall advanced age, frailty and pre-existing comorbidities of patients with MDS, SARS-Cov2 was feared to be particularly dangerous in this patient population. A recent study by Mossuto et al describes the outcomes of patients with MDS with SARS-CoV-2 infection during the Coronavirus outbreak in Italy. Among a total of 5326 patients with MDS followed during the study period, 63 (1.18%) had confirmed SARS-CoV-2 infection. With a median age of 73 years, the mortality rate among these patients was 52% compared to that of the non-MDS population (24%), and was particularly high on male MDS patients (73% of total deaths). Respiratory failure was the cause of death in all the MDS patients with ARDS in 50% of deceased patients, and with majority of patients who were able to recover having lower risk IPSS-R categories. Interestingly, no differences in mortality or severity of infection were observed based on the type of therapy received for their MDS. These findings are not surprising given the underlying inflammation and immunosuppression in patients with MDS. Until the development of COVID-19 vaccines has been completed, identification of high-risk populations and specific guidelines for the management of SARS-CoV-2 infection in patients with MDS remains of paramount importance.

Clonal hematopoiesis is a known cardiovascular risk factor which has been associated with increased risk of cardiac and cerebrovascular events. Recent studies have also associated MDS with higher than expected cardiovascular comorbidities and cardiovascular-related deaths. In accordance to prior publications by Naqvi et al, a recent study by Faber et al retrospectively evaluated 236 MDS patients and studied the associations of somatic mutations with cardiovascular risk. Overall, the authors observed that 27% of patients in their study population developed vascular event, and that ASXL1 mutations were predictive of vascular disease by multivariate analysis (with an odds ratio of 4.2). This data further supports the biological connection between comorbidities and hematopoietic clonal disorders, the role of inflammaging and the need to maximize cardiovascular risk factor care in patients with MDS and develop specific therapies targeting both the disease biology and the underlying mechanisms leading to increased cardiovascular risk.

Guillermo Montalban Bravo, MD
Assistant Professor, Department of Leukemia, Division of Cancer Medicine
MD Anderson Cancer Center, Houston, TX

The current COVID-19 pandemic has afflicted over 44 million individuals across the planet and been responsible for over 1 million deaths, particularly in high-risk populations. As a result of the overall advanced age, frailty and pre-existing comorbidities of patients with MDS, SARS-Cov2 was feared to be particularly dangerous in this patient population. A recent study by Mossuto et al describes the outcomes of patients with MDS with SARS-CoV-2 infection during the Coronavirus outbreak in Italy. Among a total of 5326 patients with MDS followed during the study period, 63 (1.18%) had confirmed SARS-CoV-2 infection. With a median age of 73 years, the mortality rate among these patients was 52% compared to that of the non-MDS population (24%), and was particularly high on male MDS patients (73% of total deaths). Respiratory failure was the cause of death in all the MDS patients with ARDS in 50% of deceased patients, and with majority of patients who were able to recover having lower risk IPSS-R categories. Interestingly, no differences in mortality or severity of infection were observed based on the type of therapy received for their MDS. These findings are not surprising given the underlying inflammation and immunosuppression in patients with MDS. Until the development of COVID-19 vaccines has been completed, identification of high-risk populations and specific guidelines for the management of SARS-CoV-2 infection in patients with MDS remains of paramount importance.

Clonal hematopoiesis is a known cardiovascular risk factor which has been associated with increased risk of cardiac and cerebrovascular events. Recent studies have also associated MDS with higher than expected cardiovascular comorbidities and cardiovascular-related deaths. In accordance to prior publications by Naqvi et al, a recent study by Faber et al retrospectively evaluated 236 MDS patients and studied the associations of somatic mutations with cardiovascular risk. Overall, the authors observed that 27% of patients in their study population developed vascular event, and that ASXL1 mutations were predictive of vascular disease by multivariate analysis (with an odds ratio of 4.2). This data further supports the biological connection between comorbidities and hematopoietic clonal disorders, the role of inflammaging and the need to maximize cardiovascular risk factor care in patients with MDS and develop specific therapies targeting both the disease biology and the underlying mechanisms leading to increased cardiovascular risk.

Guillermo Montalban Bravo, MD
Assistant Professor, Department of Leukemia, Division of Cancer Medicine
MD Anderson Cancer Center, Houston, TX

Key clinical point: Gene mutations involving ASXL1 were significantly associated with increased risk of vascular events in adults with myelodysplastic syndrome, but Trisomy 8 appeared to have a protective effect.

Major finding: Overall, the incidence of vascular disease in the study population was 27%; mutations in the ASXL1 in particular were significant predictors of vascular disease in multivariate analysis (odds ratio 4.2); however, both elevated ferritin and Trisomy 8 were significantly associated with a lower risk of vascular disease in low-risk MDS patients (P = .043 and P = .036, respectively).

Study details: The data come from a retrospective analysis of 236 MDS patients aged 18 years and older who were seen and treated at a single center between 2010 and 2018.

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.  

Citation: Faber MG et al. eJHaem. 2020 Sept 28. doi: 10.1002/jha2.101.

Key clinical point: Gene mutations involving ASXL1 were significantly associated with increased risk of vascular events in adults with myelodysplastic syndrome, but Trisomy 8 appeared to have a protective effect.

Major finding: Overall, the incidence of vascular disease in the study population was 27%; mutations in the ASXL1 in particular were significant predictors of vascular disease in multivariate analysis (odds ratio 4.2); however, both elevated ferritin and Trisomy 8 were significantly associated with a lower risk of vascular disease in low-risk MDS patients (P = .043 and P = .036, respectively).

Study details: The data come from a retrospective analysis of 236 MDS patients aged 18 years and older who were seen and treated at a single center between 2010 and 2018.

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.  

Citation: Faber MG et al. eJHaem. 2020 Sept 28. doi: 10.1002/jha2.101.

Key clinical point: Gene mutations involving ASXL1 were significantly associated with increased risk of vascular events in adults with myelodysplastic syndrome, but Trisomy 8 appeared to have a protective effect.

Major finding: Overall, the incidence of vascular disease in the study population was 27%; mutations in the ASXL1 in particular were significant predictors of vascular disease in multivariate analysis (odds ratio 4.2); however, both elevated ferritin and Trisomy 8 were significantly associated with a lower risk of vascular disease in low-risk MDS patients (P = .043 and P = .036, respectively).

Study details: The data come from a retrospective analysis of 236 MDS patients aged 18 years and older who were seen and treated at a single center between 2010 and 2018.

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.  

Citation: Faber MG et al. eJHaem. 2020 Sept 28. doi: 10.1002/jha2.101.

Key clinical point: Myelodysplastic syndrome patients who had a slower luspatercept apparent clearance (CL/F) were more likely to achieve erythroid responses, suggesting potential as an early efficacy marker.

Major finding: Luspatercept given over a dose range of 0.125 mg/kg-1.75 mg/kg yielded linear and time-invariant pharmacokinetics when given to MDS patients with anemia subcutaneously once every 3 weeks; the odds of transfusion independence at a minimum of 8 weeks increased with time-averaged exposure and plateaued at 1.0 mg/kg-1.75 mg/kg.

Study details: The data come from a review of several studies including 260 adults with anemia caused by myelodysplastic syndromes.

Disclosures: The studies in the review were funded by Bristol Myers Squibb or Acceleron. Lead author Dr. Chen and several coauthors are employees of Bristol Myers Squibb.

Citation: Chen N et al. CPT Pharmacometrics Syst Pharmacol. 2020 June 30. doi: 10.1002/psp4.12521.

Key clinical point: Myelodysplastic syndrome patients who had a slower luspatercept apparent clearance (CL/F) were more likely to achieve erythroid responses, suggesting potential as an early efficacy marker.

Major finding: Luspatercept given over a dose range of 0.125 mg/kg-1.75 mg/kg yielded linear and time-invariant pharmacokinetics when given to MDS patients with anemia subcutaneously once every 3 weeks; the odds of transfusion independence at a minimum of 8 weeks increased with time-averaged exposure and plateaued at 1.0 mg/kg-1.75 mg/kg.

Study details: The data come from a review of several studies including 260 adults with anemia caused by myelodysplastic syndromes.

Disclosures: The studies in the review were funded by Bristol Myers Squibb or Acceleron. Lead author Dr. Chen and several coauthors are employees of Bristol Myers Squibb.

Citation: Chen N et al. CPT Pharmacometrics Syst Pharmacol. 2020 June 30. doi: 10.1002/psp4.12521.

Key clinical point: Myelodysplastic syndrome patients who had a slower luspatercept apparent clearance (CL/F) were more likely to achieve erythroid responses, suggesting potential as an early efficacy marker.

Major finding: Luspatercept given over a dose range of 0.125 mg/kg-1.75 mg/kg yielded linear and time-invariant pharmacokinetics when given to MDS patients with anemia subcutaneously once every 3 weeks; the odds of transfusion independence at a minimum of 8 weeks increased with time-averaged exposure and plateaued at 1.0 mg/kg-1.75 mg/kg.

Study details: The data come from a review of several studies including 260 adults with anemia caused by myelodysplastic syndromes.

Disclosures: The studies in the review were funded by Bristol Myers Squibb or Acceleron. Lead author Dr. Chen and several coauthors are employees of Bristol Myers Squibb.

Citation: Chen N et al. CPT Pharmacometrics Syst Pharmacol. 2020 June 30. doi: 10.1002/psp4.12521.

Key clinical point: Approximately half of transfusion-dependent MDS patients said they had not discussed ways to reduce the need for transfusions with their doctors and 74% said there were no alternatives to blood transfusions.

Major finding: Among adults with MDS, those with disease duration less than 5 years cited transfusion reactions as their greatest concern; those with longer disease duration cited iron overload. However, a majority of 71% of the patients ranked their quality of life as good or excellent. MDS physicians reported that they would be most likely to offer blood transfusions as primary therapy to patients who were older than 80 years, frail, had lower risk MDS, or had other significant comorbidities.

Study details: The data come from a pair of cross-sectional surveys including 157 myelodysplastic syndrome (MDS) patients and 109 MDS physicians.

Disclosures: The study was supported by the Aplastic Anemia and MDS International Foundation through a grant from Celgene. Lead author Dr. King was supported in part by The Maren Research Award Scholarship through the University of Florida.

Citation: King D et al. Leuk Res. 2020 July 15. doi: 10.1016/j.leukres.2020.106425.

Key clinical point: Approximately half of transfusion-dependent MDS patients said they had not discussed ways to reduce the need for transfusions with their doctors and 74% said there were no alternatives to blood transfusions.

Major finding: Among adults with MDS, those with disease duration less than 5 years cited transfusion reactions as their greatest concern; those with longer disease duration cited iron overload. However, a majority of 71% of the patients ranked their quality of life as good or excellent. MDS physicians reported that they would be most likely to offer blood transfusions as primary therapy to patients who were older than 80 years, frail, had lower risk MDS, or had other significant comorbidities.

Study details: The data come from a pair of cross-sectional surveys including 157 myelodysplastic syndrome (MDS) patients and 109 MDS physicians.

Disclosures: The study was supported by the Aplastic Anemia and MDS International Foundation through a grant from Celgene. Lead author Dr. King was supported in part by The Maren Research Award Scholarship through the University of Florida.

Citation: King D et al. Leuk Res. 2020 July 15. doi: 10.1016/j.leukres.2020.106425.

Key clinical point: Approximately half of transfusion-dependent MDS patients said they had not discussed ways to reduce the need for transfusions with their doctors and 74% said there were no alternatives to blood transfusions.

Major finding: Among adults with MDS, those with disease duration less than 5 years cited transfusion reactions as their greatest concern; those with longer disease duration cited iron overload. However, a majority of 71% of the patients ranked their quality of life as good or excellent. MDS physicians reported that they would be most likely to offer blood transfusions as primary therapy to patients who were older than 80 years, frail, had lower risk MDS, or had other significant comorbidities.

Study details: The data come from a pair of cross-sectional surveys including 157 myelodysplastic syndrome (MDS) patients and 109 MDS physicians.

Disclosures: The study was supported by the Aplastic Anemia and MDS International Foundation through a grant from Celgene. Lead author Dr. King was supported in part by The Maren Research Award Scholarship through the University of Florida.

Citation: King D et al. Leuk Res. 2020 July 15. doi: 10.1016/j.leukres.2020.106425.

Key clinical point: Bronchoscopy was safe for most patients with malignant hematologic disorders with careful monitoring and use of sedatives, particularly midazolam.

Major finding: A total of 12 out of 272 patients (3.8%) experienced prolonged oxygen desaturation; 7 of these recovered and 5 died from lung lesion deterioration. However, midazolam reduced the risk of prolonged oxygen desaturation in the study population.

Study details: The data come from a review of 316 bronchoscopies in 282 adults with malignant hematologic disorders and pulmonary infiltrates who were treated at a single center.

Disclosures: Lead author Dr. Uruga disclosed grant support from Okinaka Memorial Institute for Medical Research.

Citation: Uruga H et al. BMC Pulm Med. 2020 Sep 11. doi: 10.1186/s12890-020-01283-8.

Key clinical point: Bronchoscopy was safe for most patients with malignant hematologic disorders with careful monitoring and use of sedatives, particularly midazolam.

Major finding: A total of 12 out of 272 patients (3.8%) experienced prolonged oxygen desaturation; 7 of these recovered and 5 died from lung lesion deterioration. However, midazolam reduced the risk of prolonged oxygen desaturation in the study population.

Study details: The data come from a review of 316 bronchoscopies in 282 adults with malignant hematologic disorders and pulmonary infiltrates who were treated at a single center.

Disclosures: Lead author Dr. Uruga disclosed grant support from Okinaka Memorial Institute for Medical Research.

Citation: Uruga H et al. BMC Pulm Med. 2020 Sep 11. doi: 10.1186/s12890-020-01283-8.

Key clinical point: Bronchoscopy was safe for most patients with malignant hematologic disorders with careful monitoring and use of sedatives, particularly midazolam.

Major finding: A total of 12 out of 272 patients (3.8%) experienced prolonged oxygen desaturation; 7 of these recovered and 5 died from lung lesion deterioration. However, midazolam reduced the risk of prolonged oxygen desaturation in the study population.

Study details: The data come from a review of 316 bronchoscopies in 282 adults with malignant hematologic disorders and pulmonary infiltrates who were treated at a single center.

Disclosures: Lead author Dr. Uruga disclosed grant support from Okinaka Memorial Institute for Medical Research.

Citation: Uruga H et al. BMC Pulm Med. 2020 Sep 11. doi: 10.1186/s12890-020-01283-8.

Key clinical point: Adults with end-stage renal disease who underwent dialysis for at least six months were at significantly increased risk for MDS compared with healthy controls.

Major finding: Patients with chronic renal failure who underwent dialysis were significantly more likely to develop myelodysplastic syndrome compared to healthy controls (subdistribution hazard ratio 1.60); older age also was significantly associated with increased MDS risk (sHR 1.03).

Study details: The data come from a study of 74,712 adults with chronic renal failure diagnoses between 1997 and 2013 who underwent dialysis, and matched controls. Participants were follow from index date to the first occurrence of MDS, withdrawal from the NHI program, or the last day of 2013.

Disclosures: The study used the National Health Insurance Research Database established by the National Health Research Institutes with the authorization of the Bureau of National Health Insurance, Ministry of Health and Welfare of Taiwan. The researchers had no financial conflicts to disclose.

Citation: Chang M-Y et al. Sci Rep. 2020 Sept 23. doi: 10.1038/s41598-020-72568-5.

Key clinical point: Adults with end-stage renal disease who underwent dialysis for at least six months were at significantly increased risk for MDS compared with healthy controls.

Major finding: Patients with chronic renal failure who underwent dialysis were significantly more likely to develop myelodysplastic syndrome compared to healthy controls (subdistribution hazard ratio 1.60); older age also was significantly associated with increased MDS risk (sHR 1.03).

Study details: The data come from a study of 74,712 adults with chronic renal failure diagnoses between 1997 and 2013 who underwent dialysis, and matched controls. Participants were follow from index date to the first occurrence of MDS, withdrawal from the NHI program, or the last day of 2013.

Disclosures: The study used the National Health Insurance Research Database established by the National Health Research Institutes with the authorization of the Bureau of National Health Insurance, Ministry of Health and Welfare of Taiwan. The researchers had no financial conflicts to disclose.

Citation: Chang M-Y et al. Sci Rep. 2020 Sept 23. doi: 10.1038/s41598-020-72568-5.

Key clinical point: Adults with end-stage renal disease who underwent dialysis for at least six months were at significantly increased risk for MDS compared with healthy controls.

Major finding: Patients with chronic renal failure who underwent dialysis were significantly more likely to develop myelodysplastic syndrome compared to healthy controls (subdistribution hazard ratio 1.60); older age also was significantly associated with increased MDS risk (sHR 1.03).

Study details: The data come from a study of 74,712 adults with chronic renal failure diagnoses between 1997 and 2013 who underwent dialysis, and matched controls. Participants were follow from index date to the first occurrence of MDS, withdrawal from the NHI program, or the last day of 2013.

Disclosures: The study used the National Health Insurance Research Database established by the National Health Research Institutes with the authorization of the Bureau of National Health Insurance, Ministry of Health and Welfare of Taiwan. The researchers had no financial conflicts to disclose.

Citation: Chang M-Y et al. Sci Rep. 2020 Sept 23. doi: 10.1038/s41598-020-72568-5.

Key clinical point: Several long noncoding RNAs (lncRNAs) were strongly associated with disease pathogenesis and prognosis in myelodysplastic syndrome (MDS) patients.

Major finding: Based on genome-wide profiling, lncRNA gene networks with expression of H19, WT1-AS, TCL6, and LEF1-AS1 were associated with higher-risk MDS; of these, H19 also showed promise as a therapeutic target because of its strong predictive value for lower complete remission rate of induction therapy in AML in the presence of H19 overexpression. 

Study details: The data come from a study of genetic profiling including 54 patients with MDS, 14 patients with acute myeloid leukemia with myelodysplasia-related changes (AML-MRC), and 9 healthy donors.

Disclosures: The study was supported by the Project for Conceptual Development of Research Organization from the Ministry of Health of the Czech Republic. The researchers had no financial conflicts to disclose.

Citation: Szikszai K et al. Cancers. 2020 Sept 23. doi: 10.3390/cancers12102726.

Key clinical point: Several long noncoding RNAs (lncRNAs) were strongly associated with disease pathogenesis and prognosis in myelodysplastic syndrome (MDS) patients.

Major finding: Based on genome-wide profiling, lncRNA gene networks with expression of H19, WT1-AS, TCL6, and LEF1-AS1 were associated with higher-risk MDS; of these, H19 also showed promise as a therapeutic target because of its strong predictive value for lower complete remission rate of induction therapy in AML in the presence of H19 overexpression. 

Study details: The data come from a study of genetic profiling including 54 patients with MDS, 14 patients with acute myeloid leukemia with myelodysplasia-related changes (AML-MRC), and 9 healthy donors.

Disclosures: The study was supported by the Project for Conceptual Development of Research Organization from the Ministry of Health of the Czech Republic. The researchers had no financial conflicts to disclose.

Citation: Szikszai K et al. Cancers. 2020 Sept 23. doi: 10.3390/cancers12102726.

Key clinical point: Several long noncoding RNAs (lncRNAs) were strongly associated with disease pathogenesis and prognosis in myelodysplastic syndrome (MDS) patients.

Major finding: Based on genome-wide profiling, lncRNA gene networks with expression of H19, WT1-AS, TCL6, and LEF1-AS1 were associated with higher-risk MDS; of these, H19 also showed promise as a therapeutic target because of its strong predictive value for lower complete remission rate of induction therapy in AML in the presence of H19 overexpression. 

Study details: The data come from a study of genetic profiling including 54 patients with MDS, 14 patients with acute myeloid leukemia with myelodysplasia-related changes (AML-MRC), and 9 healthy donors.

Disclosures: The study was supported by the Project for Conceptual Development of Research Organization from the Ministry of Health of the Czech Republic. The researchers had no financial conflicts to disclose.

Citation: Szikszai K et al. Cancers. 2020 Sept 23. doi: 10.3390/cancers12102726.

Key clinical point: Ferroptosis, a distinct form of regulated cell death process involving iron-dependent lipid peroxidation, may impact the action of chemotherapy drug decitabine.

Major finding: The level of GSH and the activity of GPX4 decreased, whereas the ROS level increased in MDS cells upon treatment with decitabine, which could be reversed by ferrostatin-1.

Study details: The data come from a review of cell viability assays, reactive oxygen species assays, gluthiathone assays, and

Disclosures: The study was supported in part by the National Natural Science Foundation of China, Key Technology Research and Development Program of Tianjin, Application Bases and Advanced Technology Research Program of Tianjin, and Key National Natural Science Foundation of Tianjin. The researchers had no financial conflicts to disclose.

Citation: Lv Q et al. Front. Oncol. 2020 Sept 2. doi: 10.3389/fonc.2020.01656.

Key clinical point: Ferroptosis, a distinct form of regulated cell death process involving iron-dependent lipid peroxidation, may impact the action of chemotherapy drug decitabine.

Major finding: The level of GSH and the activity of GPX4 decreased, whereas the ROS level increased in MDS cells upon treatment with decitabine, which could be reversed by ferrostatin-1.

Study details: The data come from a review of cell viability assays, reactive oxygen species assays, gluthiathone assays, and

Disclosures: The study was supported in part by the National Natural Science Foundation of China, Key Technology Research and Development Program of Tianjin, Application Bases and Advanced Technology Research Program of Tianjin, and Key National Natural Science Foundation of Tianjin. The researchers had no financial conflicts to disclose.

Citation: Lv Q et al. Front. Oncol. 2020 Sept 2. doi: 10.3389/fonc.2020.01656.

Key clinical point: Ferroptosis, a distinct form of regulated cell death process involving iron-dependent lipid peroxidation, may impact the action of chemotherapy drug decitabine.

Major finding: The level of GSH and the activity of GPX4 decreased, whereas the ROS level increased in MDS cells upon treatment with decitabine, which could be reversed by ferrostatin-1.

Study details: The data come from a review of cell viability assays, reactive oxygen species assays, gluthiathone assays, and

Disclosures: The study was supported in part by the National Natural Science Foundation of China, Key Technology Research and Development Program of Tianjin, Application Bases and Advanced Technology Research Program of Tianjin, and Key National Natural Science Foundation of Tianjin. The researchers had no financial conflicts to disclose.

Citation: Lv Q et al. Front. Oncol. 2020 Sept 2. doi: 10.3389/fonc.2020.01656.

Key clinical point: In a population of MDS patients with COVID-19 symptoms who underwent laboratory testing, 20.6% had confirmed cases.

Major finding: At the time of this analysis, 33 of 63 COVID-19 positive MDS patients were alive, suggesting a higher lethality rate in this population compared to the population at large.

Study details: The data come from a review of 5,326 adults with myelodysplastic syndromes who were symptomatic for COVID-19 between February 24 and April 28, 2020; 305 MDS patients underwent laboratory testing to confirm the infection.

Disclosures: The study was received no outside funding. The researchers had no financial conflicts to disclose.

Citation: Mossuto S et al. HemaSphere. 2020 Oct. doi: 10.1097/HS9.0000000000000483.

Key clinical point: In a population of MDS patients with COVID-19 symptoms who underwent laboratory testing, 20.6% had confirmed cases.

Major finding: At the time of this analysis, 33 of 63 COVID-19 positive MDS patients were alive, suggesting a higher lethality rate in this population compared to the population at large.

Study details: The data come from a review of 5,326 adults with myelodysplastic syndromes who were symptomatic for COVID-19 between February 24 and April 28, 2020; 305 MDS patients underwent laboratory testing to confirm the infection.

Disclosures: The study was received no outside funding. The researchers had no financial conflicts to disclose.

Citation: Mossuto S et al. HemaSphere. 2020 Oct. doi: 10.1097/HS9.0000000000000483.

Key clinical point: In a population of MDS patients with COVID-19 symptoms who underwent laboratory testing, 20.6% had confirmed cases.

Major finding: At the time of this analysis, 33 of 63 COVID-19 positive MDS patients were alive, suggesting a higher lethality rate in this population compared to the population at large.

Study details: The data come from a review of 5,326 adults with myelodysplastic syndromes who were symptomatic for COVID-19 between February 24 and April 28, 2020; 305 MDS patients underwent laboratory testing to confirm the infection.

Disclosures: The study was received no outside funding. The researchers had no financial conflicts to disclose.

Citation: Mossuto S et al. HemaSphere. 2020 Oct. doi: 10.1097/HS9.0000000000000483.

Prognoses remain extremely poor after hypomethylating agents (HMAs) fail in patients with higher-risk myelodysplastic syndromes (HR-MDS). But a hematologist-oncologist told colleagues that novel therapies are in the works, and some show promise.

Still, “the clinical development for drugs in this setting has been quite challenging, and we have had a lot of drugs that have died in this space over the years,” cautioned Amer Zeidan, MBBS, MHS, an associate professor at Yale University, New Haven, Conn., in a presentation at the virtual Acute Leukemia Forum of Hemedicus. For now, “the best way to manage HMA failure in MDS patients is by preventing HMA failure.”

Dr. Zeidan highlighted a 2016 study – which he led – that found the median overall survival from diagnosis was just a median of 17.0 months (95% confidence interval, 15.8-18.4) in 632 patients with HR-MDS. Another 2016 study, which he also led, reported median overall survival of 11 months (95% CI, 10-14) and 12 months (95% CI, 11-16; P = .26) for patients aged 66 or older who had HR-MDS and took azacitidine and decitabine, respectively. Median survival is even shorter after HMA failure, he said.

The most important obstacle to effective therapy is “the biologic and molecular heterogeneity of the disease,” he said. “Only a certain number of genes are altered in a significant number of patients. And then you have a very long tail, with so many alterations, but most of them are rare. That makes targeting all patients with the same mechanism quite challenging. Also, we poorly understand how hypomethylating agents work and the mechanism of primary and secondary failure. And many MDS patients are older with multiple conditions, multiple comorbidities. By the time of failure, they are generally beaten up and very difficult to enroll in clinical trials.”

Even so, he said, “the understanding of the molecular pathogenesis of MDS is starting to open the door for new drug development opportunities. What’s been changing over the last 5 years is an increased understanding of targeting some of the alterations that are specific to the patient – individualized targeting or precision medicine.”
 

Novel therapies

Dr. Zeidan said the novel therapies for HR-MDS after HMA failure fall into these categories: molecularly targeted agents, genetically agnostic small-molecule inhibitors, immunotherapies, and chemotherapy/epigenetic agents.

Multiple trials, for example, are examining a chemotherapy treatment CPX-351 (liposomal cytarabine-daunorubicin) in HR-MDS, and a 2018 study showed improvement in median survival in older patients with newly diagnosed secondary acute myeloid leukemia. “However, this remains an investigational treatment,” Dr. Zeidan cautioned.

Venetoclax is also being studied. Animal and cell culture data suggest there may be helpful synergistic activity between venetoclax and azacitidine in both the frontline and relapse settings. Dr. Zeidan highlighted his own 2019 report on a phase 1b study of venetoclax versus venetoclax and azacitidine in the HMA failure/HR-MDS setting. The results are “quite exciting,” he said.

The report noted that, “although the study is still ongoing, the 6-month OS [overall survival] estimate of 57% in monotherapy [patients] compares favorably to historical controls.”

Glasdegib is “another drug of interest,” although it’s mostly been studied in the frontline setting, he said, and “we don’t have much data with this drug in the refractory setting for MDS patients.” APR-246 is also intriguing, he said, but again lacks data in the refractory setting.

Dr. Zeidan noted research into other treatments – rigosertib (recent findings have been disappointing), ivosidenib for IDH1-mutated MDS, AG221-001 and enasidenib (targeting IDH2 mutations), trametinib (targeting RAS pathway mutations), and others. For now, “clinical trial participation should be the best way to manage these patients.”

Dr. Zeidan disclosed multiple disclosures, including relationships with Pfizer, Novartis, Abbvie, Pfizer, Medimmune/AstraZeneca and Boehringer Ingelheim, among others.

The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.

Prognoses remain extremely poor after hypomethylating agents (HMAs) fail in patients with higher-risk myelodysplastic syndromes (HR-MDS). But a hematologist-oncologist told colleagues that novel therapies are in the works, and some show promise.

Still, “the clinical development for drugs in this setting has been quite challenging, and we have had a lot of drugs that have died in this space over the years,” cautioned Amer Zeidan, MBBS, MHS, an associate professor at Yale University, New Haven, Conn., in a presentation at the virtual Acute Leukemia Forum of Hemedicus. For now, “the best way to manage HMA failure in MDS patients is by preventing HMA failure.”

Dr. Zeidan highlighted a 2016 study – which he led – that found the median overall survival from diagnosis was just a median of 17.0 months (95% confidence interval, 15.8-18.4) in 632 patients with HR-MDS. Another 2016 study, which he also led, reported median overall survival of 11 months (95% CI, 10-14) and 12 months (95% CI, 11-16; P = .26) for patients aged 66 or older who had HR-MDS and took azacitidine and decitabine, respectively. Median survival is even shorter after HMA failure, he said.

The most important obstacle to effective therapy is “the biologic and molecular heterogeneity of the disease,” he said. “Only a certain number of genes are altered in a significant number of patients. And then you have a very long tail, with so many alterations, but most of them are rare. That makes targeting all patients with the same mechanism quite challenging. Also, we poorly understand how hypomethylating agents work and the mechanism of primary and secondary failure. And many MDS patients are older with multiple conditions, multiple comorbidities. By the time of failure, they are generally beaten up and very difficult to enroll in clinical trials.”

Even so, he said, “the understanding of the molecular pathogenesis of MDS is starting to open the door for new drug development opportunities. What’s been changing over the last 5 years is an increased understanding of targeting some of the alterations that are specific to the patient – individualized targeting or precision medicine.”
 

Novel therapies

Dr. Zeidan said the novel therapies for HR-MDS after HMA failure fall into these categories: molecularly targeted agents, genetically agnostic small-molecule inhibitors, immunotherapies, and chemotherapy/epigenetic agents.

Multiple trials, for example, are examining a chemotherapy treatment CPX-351 (liposomal cytarabine-daunorubicin) in HR-MDS, and a 2018 study showed improvement in median survival in older patients with newly diagnosed secondary acute myeloid leukemia. “However, this remains an investigational treatment,” Dr. Zeidan cautioned.

Venetoclax is also being studied. Animal and cell culture data suggest there may be helpful synergistic activity between venetoclax and azacitidine in both the frontline and relapse settings. Dr. Zeidan highlighted his own 2019 report on a phase 1b study of venetoclax versus venetoclax and azacitidine in the HMA failure/HR-MDS setting. The results are “quite exciting,” he said.

The report noted that, “although the study is still ongoing, the 6-month OS [overall survival] estimate of 57% in monotherapy [patients] compares favorably to historical controls.”

Glasdegib is “another drug of interest,” although it’s mostly been studied in the frontline setting, he said, and “we don’t have much data with this drug in the refractory setting for MDS patients.” APR-246 is also intriguing, he said, but again lacks data in the refractory setting.

Dr. Zeidan noted research into other treatments – rigosertib (recent findings have been disappointing), ivosidenib for IDH1-mutated MDS, AG221-001 and enasidenib (targeting IDH2 mutations), trametinib (targeting RAS pathway mutations), and others. For now, “clinical trial participation should be the best way to manage these patients.”

Dr. Zeidan disclosed multiple disclosures, including relationships with Pfizer, Novartis, Abbvie, Pfizer, Medimmune/AstraZeneca and Boehringer Ingelheim, among others.

The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.

Prognoses remain extremely poor after hypomethylating agents (HMAs) fail in patients with higher-risk myelodysplastic syndromes (HR-MDS). But a hematologist-oncologist told colleagues that novel therapies are in the works, and some show promise.

Still, “the clinical development for drugs in this setting has been quite challenging, and we have had a lot of drugs that have died in this space over the years,” cautioned Amer Zeidan, MBBS, MHS, an associate professor at Yale University, New Haven, Conn., in a presentation at the virtual Acute Leukemia Forum of Hemedicus. For now, “the best way to manage HMA failure in MDS patients is by preventing HMA failure.”

Dr. Zeidan highlighted a 2016 study – which he led – that found the median overall survival from diagnosis was just a median of 17.0 months (95% confidence interval, 15.8-18.4) in 632 patients with HR-MDS. Another 2016 study, which he also led, reported median overall survival of 11 months (95% CI, 10-14) and 12 months (95% CI, 11-16; P = .26) for patients aged 66 or older who had HR-MDS and took azacitidine and decitabine, respectively. Median survival is even shorter after HMA failure, he said.

The most important obstacle to effective therapy is “the biologic and molecular heterogeneity of the disease,” he said. “Only a certain number of genes are altered in a significant number of patients. And then you have a very long tail, with so many alterations, but most of them are rare. That makes targeting all patients with the same mechanism quite challenging. Also, we poorly understand how hypomethylating agents work and the mechanism of primary and secondary failure. And many MDS patients are older with multiple conditions, multiple comorbidities. By the time of failure, they are generally beaten up and very difficult to enroll in clinical trials.”

Even so, he said, “the understanding of the molecular pathogenesis of MDS is starting to open the door for new drug development opportunities. What’s been changing over the last 5 years is an increased understanding of targeting some of the alterations that are specific to the patient – individualized targeting or precision medicine.”
 

Novel therapies

Dr. Zeidan said the novel therapies for HR-MDS after HMA failure fall into these categories: molecularly targeted agents, genetically agnostic small-molecule inhibitors, immunotherapies, and chemotherapy/epigenetic agents.

Multiple trials, for example, are examining a chemotherapy treatment CPX-351 (liposomal cytarabine-daunorubicin) in HR-MDS, and a 2018 study showed improvement in median survival in older patients with newly diagnosed secondary acute myeloid leukemia. “However, this remains an investigational treatment,” Dr. Zeidan cautioned.

Venetoclax is also being studied. Animal and cell culture data suggest there may be helpful synergistic activity between venetoclax and azacitidine in both the frontline and relapse settings. Dr. Zeidan highlighted his own 2019 report on a phase 1b study of venetoclax versus venetoclax and azacitidine in the HMA failure/HR-MDS setting. The results are “quite exciting,” he said.

The report noted that, “although the study is still ongoing, the 6-month OS [overall survival] estimate of 57% in monotherapy [patients] compares favorably to historical controls.”

Glasdegib is “another drug of interest,” although it’s mostly been studied in the frontline setting, he said, and “we don’t have much data with this drug in the refractory setting for MDS patients.” APR-246 is also intriguing, he said, but again lacks data in the refractory setting.

Dr. Zeidan noted research into other treatments – rigosertib (recent findings have been disappointing), ivosidenib for IDH1-mutated MDS, AG221-001 and enasidenib (targeting IDH2 mutations), trametinib (targeting RAS pathway mutations), and others. For now, “clinical trial participation should be the best way to manage these patients.”

Dr. Zeidan disclosed multiple disclosures, including relationships with Pfizer, Novartis, Abbvie, Pfizer, Medimmune/AstraZeneca and Boehringer Ingelheim, among others.

The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.