Key clinical point: This study found no evidence of an association between nonsteroidal anti-inflammatory drug (NSAID) use and myelodysplastic syndromes (MDS).

Major finding: No significant association was seen between MDS and use of any NSAID (adjusted odds ratio [aOR], 0.92; 95% confidence interval [CI], 0.68-1.23), aspirin (aOR, 0.87; 95% CI, 0.67-1.14), ibuprofen (aOR, 0.91; 95% CI, 0.64-1.30), or acetaminophen (aOR, 1.29; 95% CI, 0.90-1.84). No association was observed in analyses stratified by sex; however, the direction of the effect between NSAID use and MDS varied by MDS subtype.

Study details: This population-based case-control study included 399 MDS cases and 698 controls using data from the Adults in Minnesota with Myelodysplastic Syndromes Study.

Disclosures: The study was funded by a National Institutes of Health grant. The authors declared no conflicts of interest.

Source: Hubbard AK et al. Leuk Lymphoma. 2021 Jan 8. doi: 10.1080/10428194.2020.

Key clinical point: This study found no evidence of an association between nonsteroidal anti-inflammatory drug (NSAID) use and myelodysplastic syndromes (MDS).

Major finding: No significant association was seen between MDS and use of any NSAID (adjusted odds ratio [aOR], 0.92; 95% confidence interval [CI], 0.68-1.23), aspirin (aOR, 0.87; 95% CI, 0.67-1.14), ibuprofen (aOR, 0.91; 95% CI, 0.64-1.30), or acetaminophen (aOR, 1.29; 95% CI, 0.90-1.84). No association was observed in analyses stratified by sex; however, the direction of the effect between NSAID use and MDS varied by MDS subtype.

Study details: This population-based case-control study included 399 MDS cases and 698 controls using data from the Adults in Minnesota with Myelodysplastic Syndromes Study.

Disclosures: The study was funded by a National Institutes of Health grant. The authors declared no conflicts of interest.

Source: Hubbard AK et al. Leuk Lymphoma. 2021 Jan 8. doi: 10.1080/10428194.2020.

Key clinical point: This study found no evidence of an association between nonsteroidal anti-inflammatory drug (NSAID) use and myelodysplastic syndromes (MDS).

Major finding: No significant association was seen between MDS and use of any NSAID (adjusted odds ratio [aOR], 0.92; 95% confidence interval [CI], 0.68-1.23), aspirin (aOR, 0.87; 95% CI, 0.67-1.14), ibuprofen (aOR, 0.91; 95% CI, 0.64-1.30), or acetaminophen (aOR, 1.29; 95% CI, 0.90-1.84). No association was observed in analyses stratified by sex; however, the direction of the effect between NSAID use and MDS varied by MDS subtype.

Study details: This population-based case-control study included 399 MDS cases and 698 controls using data from the Adults in Minnesota with Myelodysplastic Syndromes Study.

Disclosures: The study was funded by a National Institutes of Health grant. The authors declared no conflicts of interest.

Source: Hubbard AK et al. Leuk Lymphoma. 2021 Jan 8. doi: 10.1080/10428194.2020.

Key clinical point: A study found smoking, history of autoimmune disease and benzene exposure to significant risk factors for de novo myelodysplastic syndromes (MDS). These factors also had a similar yet non-significant association with therapy-related MDS (tMDS).

Major finding:  After adjusting for confounders, former smoking status (odds ratio [OR], 1.45; 95% confidence interval [CI], 1.10-1.93), history of autoimmune disease (OR, 1.34; 95% CI, 0.99-1.82) and benzene exposure (OR, 1.48; 95% CI, 1.00-2.19) were significantly associated with de novo MDS. The risk estimates for these associations were similar in magnitude for tMDS, but non-significant.

Study details: The data come from a case-control study involving 346 de novo MDS cases, 37 tMDS cases and 682 controls matched by age and sex.

Disclosures: The study was funded by the National Institutes of Health. The authors declared no conflicts of interest.

Source: Yarosh R et al. Cancer Causes Control. 2021 Jan 4. doi: 10.1007/s10552-020-01378-x.

Key clinical point: A study found smoking, history of autoimmune disease and benzene exposure to significant risk factors for de novo myelodysplastic syndromes (MDS). These factors also had a similar yet non-significant association with therapy-related MDS (tMDS).

Major finding:  After adjusting for confounders, former smoking status (odds ratio [OR], 1.45; 95% confidence interval [CI], 1.10-1.93), history of autoimmune disease (OR, 1.34; 95% CI, 0.99-1.82) and benzene exposure (OR, 1.48; 95% CI, 1.00-2.19) were significantly associated with de novo MDS. The risk estimates for these associations were similar in magnitude for tMDS, but non-significant.

Study details: The data come from a case-control study involving 346 de novo MDS cases, 37 tMDS cases and 682 controls matched by age and sex.

Disclosures: The study was funded by the National Institutes of Health. The authors declared no conflicts of interest.

Source: Yarosh R et al. Cancer Causes Control. 2021 Jan 4. doi: 10.1007/s10552-020-01378-x.

Key clinical point: A study found smoking, history of autoimmune disease and benzene exposure to significant risk factors for de novo myelodysplastic syndromes (MDS). These factors also had a similar yet non-significant association with therapy-related MDS (tMDS).

Major finding:  After adjusting for confounders, former smoking status (odds ratio [OR], 1.45; 95% confidence interval [CI], 1.10-1.93), history of autoimmune disease (OR, 1.34; 95% CI, 0.99-1.82) and benzene exposure (OR, 1.48; 95% CI, 1.00-2.19) were significantly associated with de novo MDS. The risk estimates for these associations were similar in magnitude for tMDS, but non-significant.

Study details: The data come from a case-control study involving 346 de novo MDS cases, 37 tMDS cases and 682 controls matched by age and sex.

Disclosures: The study was funded by the National Institutes of Health. The authors declared no conflicts of interest.

Source: Yarosh R et al. Cancer Causes Control. 2021 Jan 4. doi: 10.1007/s10552-020-01378-x.

Key clinical point: Myelodysplastic syndrome (MDS) patients treated with hypomethylating agents (HMA), especially those with higher-risk MDS have unmet clinical needs in real-world setting.

Major finding: Median survival was 11.6 months, 18.4 months, and 19.1 months for the higher-risk, intermediate-risk, and unknown-risk groups, respectively. Corresponding median time-to-AML transformation for the 3 groups were 19.3 months, 50.4 months, and 'not reached', respectively.

Study details: The data come from 3,046 MDS patients treated with HMA from the SEER-Medicare database. The patients were categorized as higher-risk, intermediate-risk, and unknown-risk.

Disclosures: The study was sponsored by Novartis. I Sadek and X Cao are employees and stockholders of Novartis.  G Bonifacio was an employee and stockholder of Novartis at the time of the study. EM Stein provided paid consulting services to Novartis. D Latremouille-Viau, S Shi, A Guerin, and EQ Wu are employees of Analysis Group, Inc. which provided paid consulting services to Novartis.

Source: Stein EM et al. Leuk Lymphoma. 2021 Jan 11. doi: 10.1080/10428194.2020.1869959.

Key clinical point: Myelodysplastic syndrome (MDS) patients treated with hypomethylating agents (HMA), especially those with higher-risk MDS have unmet clinical needs in real-world setting.

Major finding: Median survival was 11.6 months, 18.4 months, and 19.1 months for the higher-risk, intermediate-risk, and unknown-risk groups, respectively. Corresponding median time-to-AML transformation for the 3 groups were 19.3 months, 50.4 months, and 'not reached', respectively.

Study details: The data come from 3,046 MDS patients treated with HMA from the SEER-Medicare database. The patients were categorized as higher-risk, intermediate-risk, and unknown-risk.

Disclosures: The study was sponsored by Novartis. I Sadek and X Cao are employees and stockholders of Novartis.  G Bonifacio was an employee and stockholder of Novartis at the time of the study. EM Stein provided paid consulting services to Novartis. D Latremouille-Viau, S Shi, A Guerin, and EQ Wu are employees of Analysis Group, Inc. which provided paid consulting services to Novartis.

Source: Stein EM et al. Leuk Lymphoma. 2021 Jan 11. doi: 10.1080/10428194.2020.1869959.

Key clinical point: Myelodysplastic syndrome (MDS) patients treated with hypomethylating agents (HMA), especially those with higher-risk MDS have unmet clinical needs in real-world setting.

Major finding: Median survival was 11.6 months, 18.4 months, and 19.1 months for the higher-risk, intermediate-risk, and unknown-risk groups, respectively. Corresponding median time-to-AML transformation for the 3 groups were 19.3 months, 50.4 months, and 'not reached', respectively.

Study details: The data come from 3,046 MDS patients treated with HMA from the SEER-Medicare database. The patients were categorized as higher-risk, intermediate-risk, and unknown-risk.

Disclosures: The study was sponsored by Novartis. I Sadek and X Cao are employees and stockholders of Novartis.  G Bonifacio was an employee and stockholder of Novartis at the time of the study. EM Stein provided paid consulting services to Novartis. D Latremouille-Viau, S Shi, A Guerin, and EQ Wu are employees of Analysis Group, Inc. which provided paid consulting services to Novartis.

Source: Stein EM et al. Leuk Lymphoma. 2021 Jan 11. doi: 10.1080/10428194.2020.1869959.

Key clinical point: Preliminary data of a phase 2 study found that the combination of azacitidine and pembrolizumab was well-tolerated and demonstrated antitumor activity in treatment-naïve patients with higher-Risk myelodysplastic syndrome (MDS)

Major finding: The overall response rate was 80%, with 3 patients reaching complete remission, 4 patients achieving marrow CR (mCR), 4 patients achieving mCR with hematologic improvement (HI), and 1 patient demonstrating HI. Treatment was well-tolerated, the most common treatment-related adverse events being arthralgia, pneumonia, nausea, and skin rash.

Study details: The preliminary phase 2 trial data come from 17 treatment-naïve patients treated with frontline combination of azacitidine and pembrolizumab, with a median follow-up time of 13.8 months and 5 patients continuing on treatment in cycles 4-28.

Disclosures: The study is sponsored by M.D. Anderson Cancer Center. The authors reported relationships with various pharmaceutical companies and/or research organizations.

Source: Chien KS et al. ASH 2020. 2020 Dec 5. Abstract 1288.

Key clinical point: Preliminary data of a phase 2 study found that the combination of azacitidine and pembrolizumab was well-tolerated and demonstrated antitumor activity in treatment-naïve patients with higher-Risk myelodysplastic syndrome (MDS)

Major finding: The overall response rate was 80%, with 3 patients reaching complete remission, 4 patients achieving marrow CR (mCR), 4 patients achieving mCR with hematologic improvement (HI), and 1 patient demonstrating HI. Treatment was well-tolerated, the most common treatment-related adverse events being arthralgia, pneumonia, nausea, and skin rash.

Study details: The preliminary phase 2 trial data come from 17 treatment-naïve patients treated with frontline combination of azacitidine and pembrolizumab, with a median follow-up time of 13.8 months and 5 patients continuing on treatment in cycles 4-28.

Disclosures: The study is sponsored by M.D. Anderson Cancer Center. The authors reported relationships with various pharmaceutical companies and/or research organizations.

Source: Chien KS et al. ASH 2020. 2020 Dec 5. Abstract 1288.

Key clinical point: Preliminary data of a phase 2 study found that the combination of azacitidine and pembrolizumab was well-tolerated and demonstrated antitumor activity in treatment-naïve patients with higher-Risk myelodysplastic syndrome (MDS)

Major finding: The overall response rate was 80%, with 3 patients reaching complete remission, 4 patients achieving marrow CR (mCR), 4 patients achieving mCR with hematologic improvement (HI), and 1 patient demonstrating HI. Treatment was well-tolerated, the most common treatment-related adverse events being arthralgia, pneumonia, nausea, and skin rash.

Study details: The preliminary phase 2 trial data come from 17 treatment-naïve patients treated with frontline combination of azacitidine and pembrolizumab, with a median follow-up time of 13.8 months and 5 patients continuing on treatment in cycles 4-28.

Disclosures: The study is sponsored by M.D. Anderson Cancer Center. The authors reported relationships with various pharmaceutical companies and/or research organizations.

Source: Chien KS et al. ASH 2020. 2020 Dec 5. Abstract 1288.

Key clinical point: Older patients with advanced myelodysplastic syndrome (MDS) may benefit from allogeneic hematopoietic cell transplantation (HCT), which is usually reserved for younger patients.

Major finding: At 3 years, the donor vs no-donor group had a greater improvement in overall survival (absolute difference, 21.3%; P = .0001) and higher leukemia-free survival (35.8% vs 20.6%; P = .003).

Study details: The study included patients aged 50-75 years with newly diagnosed MDS of higher risk and who were eligible for reduced-intensity conditioning (RIC) allogeneic HCT. Patients were initially assigned to the "no-donor" group at enrollment and reassigned to the donor group when a suitable donor was identified.

Disclosures: No specific funding information was available for the study. The authors reported relationships with various pharmaceutical companies and/or research organizations.

Source: Nakamura R et al. ASH 2020. 2020 Dec 5. Abstract 75.

Key clinical point: Older patients with advanced myelodysplastic syndrome (MDS) may benefit from allogeneic hematopoietic cell transplantation (HCT), which is usually reserved for younger patients.

Major finding: At 3 years, the donor vs no-donor group had a greater improvement in overall survival (absolute difference, 21.3%; P = .0001) and higher leukemia-free survival (35.8% vs 20.6%; P = .003).

Study details: The study included patients aged 50-75 years with newly diagnosed MDS of higher risk and who were eligible for reduced-intensity conditioning (RIC) allogeneic HCT. Patients were initially assigned to the "no-donor" group at enrollment and reassigned to the donor group when a suitable donor was identified.

Disclosures: No specific funding information was available for the study. The authors reported relationships with various pharmaceutical companies and/or research organizations.

Source: Nakamura R et al. ASH 2020. 2020 Dec 5. Abstract 75.

Key clinical point: Older patients with advanced myelodysplastic syndrome (MDS) may benefit from allogeneic hematopoietic cell transplantation (HCT), which is usually reserved for younger patients.

Major finding: At 3 years, the donor vs no-donor group had a greater improvement in overall survival (absolute difference, 21.3%; P = .0001) and higher leukemia-free survival (35.8% vs 20.6%; P = .003).

Study details: The study included patients aged 50-75 years with newly diagnosed MDS of higher risk and who were eligible for reduced-intensity conditioning (RIC) allogeneic HCT. Patients were initially assigned to the "no-donor" group at enrollment and reassigned to the donor group when a suitable donor was identified.

Disclosures: No specific funding information was available for the study. The authors reported relationships with various pharmaceutical companies and/or research organizations.

Source: Nakamura R et al. ASH 2020. 2020 Dec 5. Abstract 75.

Key clinical point: Poly (ADP-ribose) polymerase (PARP) inhibitors were associated with an increased risk for myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML).

Major finding: Meta-analysis of 18 placebo randomized clinical trials (n=7,307) revealed an increased risk for MDS and AML with PARP inhibitors vs. placebo (Peto odds ratio, 2.63; P = .026). The incidence of MDS and AML across PARP inhibitor groups was 0.73% vs. 0.47% for placebo groups. In VigiBase, median treatment duration was 9.8 months and median latency period since first exposure to a PARP inhibitor was 17.8 months. Of 104 cases of MDS/AML that reported outcomes, 45% of cases resulted in death.

Study details: This study estimated the risk of MDS and AML related to PARP inhibitors, via a systematic review and safety meta-analysis, and described clinical features of PARP inhibitor-related MDS (n = 99) and AML (n = 79) cases reported in VigiBase, the WHO’s pharmacovigilance database.

Disclosures: The study did not receive any funding. Some study investigators reported receiving grants and personal fees from various pharmaceutical companies outside the submitted work.

Source: Morice PM et al. Lancet Haematol. 2020 Dec 18. doi: 10.1016/S2352-3026(20)30360-4.

Key clinical point: Poly (ADP-ribose) polymerase (PARP) inhibitors were associated with an increased risk for myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML).

Major finding: Meta-analysis of 18 placebo randomized clinical trials (n=7,307) revealed an increased risk for MDS and AML with PARP inhibitors vs. placebo (Peto odds ratio, 2.63; P = .026). The incidence of MDS and AML across PARP inhibitor groups was 0.73% vs. 0.47% for placebo groups. In VigiBase, median treatment duration was 9.8 months and median latency period since first exposure to a PARP inhibitor was 17.8 months. Of 104 cases of MDS/AML that reported outcomes, 45% of cases resulted in death.

Study details: This study estimated the risk of MDS and AML related to PARP inhibitors, via a systematic review and safety meta-analysis, and described clinical features of PARP inhibitor-related MDS (n = 99) and AML (n = 79) cases reported in VigiBase, the WHO’s pharmacovigilance database.

Disclosures: The study did not receive any funding. Some study investigators reported receiving grants and personal fees from various pharmaceutical companies outside the submitted work.

Source: Morice PM et al. Lancet Haematol. 2020 Dec 18. doi: 10.1016/S2352-3026(20)30360-4.

Key clinical point: Poly (ADP-ribose) polymerase (PARP) inhibitors were associated with an increased risk for myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML).

Major finding: Meta-analysis of 18 placebo randomized clinical trials (n=7,307) revealed an increased risk for MDS and AML with PARP inhibitors vs. placebo (Peto odds ratio, 2.63; P = .026). The incidence of MDS and AML across PARP inhibitor groups was 0.73% vs. 0.47% for placebo groups. In VigiBase, median treatment duration was 9.8 months and median latency period since first exposure to a PARP inhibitor was 17.8 months. Of 104 cases of MDS/AML that reported outcomes, 45% of cases resulted in death.

Study details: This study estimated the risk of MDS and AML related to PARP inhibitors, via a systematic review and safety meta-analysis, and described clinical features of PARP inhibitor-related MDS (n = 99) and AML (n = 79) cases reported in VigiBase, the WHO’s pharmacovigilance database.

Disclosures: The study did not receive any funding. Some study investigators reported receiving grants and personal fees from various pharmaceutical companies outside the submitted work.

Source: Morice PM et al. Lancet Haematol. 2020 Dec 18. doi: 10.1016/S2352-3026(20)30360-4.

Currently there are limited therapeutic options for myelodysplastic syndromes (MDS) after failure of standard therapy. Options for patients with lower risk MDS patients without presence of deletion 5q (del5q) or SF3B1 mutation are limited after growth factor support. Lenalidomide has been used as a single agent in patients with low risk non-del5q MDS refractory to erythropoietin stimulating agents (ESA) with limited erythroid response. A phase III US intergroup trial  compared erythroid response in low risk MDS non-del5q MDS patients after ESA to either combination of lenalidomide and epoetin alfa (EPO) versus lenalidomide alone. After four cycles of treatment, major erythroid response was higher in the combination group compared to lenalidomide alone (28.3% vs 11.5%, p=0.004). The response was durable, with median major erythroid response duration of 23.8 months compared to 13 months for lenalidomide alone. In patients with low risk MDS with del5q where lenalidomide is considered, lenalidomide should be considered in combination with epoetin alfa.

For higher risk MDS patients, standard upfront treatment is hypomethylating agents (HMA), either azacitidine or decitabine. Given increased PD-1 and PD-L1 expression in high risk MDS, pembrolizumab, a monoclonal antibody targeting PD-1, is currently being evaluated in MDS. Updated results of a phase II study evaluating combination of pembrolizumab and azacitidine in untreated higher risk MDS patients was reported in ASH 2020. Untreated MDS patients with intermediate-1 and high risk by IPSS were enrolled and treated with standard azacitidine in combination with pembrolizumab 200mg IV on day 1 every 21 days. Out of 17 patients, overall response rate was 80%, with 3 patients achieving complete remission (CR), 4 patients achieving marrow CR, 4 patients achieving marrow CR with hematologic improvement, and one patient demonstrating hematologic improvement of erythrocytes. Median overall survival was not reached with median follow up of 13.8 months. Pembrolizumab with azacitidine should be further investigated in MDS.

Poly(ADP-ribose) polymerase (PARP) inhibitors are utilized in a range of solid tumor cancers. There are emerging concerns of PARP inhibitors with increased risk of developing MDS and acute myeloid leukemia (AML). A meta-analysis of 28 randomized control trials (RCT) with PARP inhibitors was done to evaluate risk of developing MDS and AML. Based on 18 RCTs with placebo control, PARP inhibitors increased risk of MDS and AML compared to placebo (Peto OR 2.63, p=0.026).  There was increased incidence of MDS and AML in the PARP inhibitor group compared to placebo (0.73% vs 0.47%). The median treatment duration was 9.8 months and median latency period since first exposure to a PARP inhibitor was 17.8 months. Use of PARP inhibitors is associated with increased risk of development of MDS and AML, and patients should be monitored accordingly.

Currently there are limited therapeutic options for myelodysplastic syndromes (MDS) after failure of standard therapy. Options for patients with lower risk MDS patients without presence of deletion 5q (del5q) or SF3B1 mutation are limited after growth factor support. Lenalidomide has been used as a single agent in patients with low risk non-del5q MDS refractory to erythropoietin stimulating agents (ESA) with limited erythroid response. A phase III US intergroup trial  compared erythroid response in low risk MDS non-del5q MDS patients after ESA to either combination of lenalidomide and epoetin alfa (EPO) versus lenalidomide alone. After four cycles of treatment, major erythroid response was higher in the combination group compared to lenalidomide alone (28.3% vs 11.5%, p=0.004). The response was durable, with median major erythroid response duration of 23.8 months compared to 13 months for lenalidomide alone. In patients with low risk MDS with del5q where lenalidomide is considered, lenalidomide should be considered in combination with epoetin alfa.

For higher risk MDS patients, standard upfront treatment is hypomethylating agents (HMA), either azacitidine or decitabine. Given increased PD-1 and PD-L1 expression in high risk MDS, pembrolizumab, a monoclonal antibody targeting PD-1, is currently being evaluated in MDS. Updated results of a phase II study evaluating combination of pembrolizumab and azacitidine in untreated higher risk MDS patients was reported in ASH 2020. Untreated MDS patients with intermediate-1 and high risk by IPSS were enrolled and treated with standard azacitidine in combination with pembrolizumab 200mg IV on day 1 every 21 days. Out of 17 patients, overall response rate was 80%, with 3 patients achieving complete remission (CR), 4 patients achieving marrow CR, 4 patients achieving marrow CR with hematologic improvement, and one patient demonstrating hematologic improvement of erythrocytes. Median overall survival was not reached with median follow up of 13.8 months. Pembrolizumab with azacitidine should be further investigated in MDS.

Poly(ADP-ribose) polymerase (PARP) inhibitors are utilized in a range of solid tumor cancers. There are emerging concerns of PARP inhibitors with increased risk of developing MDS and acute myeloid leukemia (AML). A meta-analysis of 28 randomized control trials (RCT) with PARP inhibitors was done to evaluate risk of developing MDS and AML. Based on 18 RCTs with placebo control, PARP inhibitors increased risk of MDS and AML compared to placebo (Peto OR 2.63, p=0.026).  There was increased incidence of MDS and AML in the PARP inhibitor group compared to placebo (0.73% vs 0.47%). The median treatment duration was 9.8 months and median latency period since first exposure to a PARP inhibitor was 17.8 months. Use of PARP inhibitors is associated with increased risk of development of MDS and AML, and patients should be monitored accordingly.

Currently there are limited therapeutic options for myelodysplastic syndromes (MDS) after failure of standard therapy. Options for patients with lower risk MDS patients without presence of deletion 5q (del5q) or SF3B1 mutation are limited after growth factor support. Lenalidomide has been used as a single agent in patients with low risk non-del5q MDS refractory to erythropoietin stimulating agents (ESA) with limited erythroid response. A phase III US intergroup trial  compared erythroid response in low risk MDS non-del5q MDS patients after ESA to either combination of lenalidomide and epoetin alfa (EPO) versus lenalidomide alone. After four cycles of treatment, major erythroid response was higher in the combination group compared to lenalidomide alone (28.3% vs 11.5%, p=0.004). The response was durable, with median major erythroid response duration of 23.8 months compared to 13 months for lenalidomide alone. In patients with low risk MDS with del5q where lenalidomide is considered, lenalidomide should be considered in combination with epoetin alfa.

For higher risk MDS patients, standard upfront treatment is hypomethylating agents (HMA), either azacitidine or decitabine. Given increased PD-1 and PD-L1 expression in high risk MDS, pembrolizumab, a monoclonal antibody targeting PD-1, is currently being evaluated in MDS. Updated results of a phase II study evaluating combination of pembrolizumab and azacitidine in untreated higher risk MDS patients was reported in ASH 2020. Untreated MDS patients with intermediate-1 and high risk by IPSS were enrolled and treated with standard azacitidine in combination with pembrolizumab 200mg IV on day 1 every 21 days. Out of 17 patients, overall response rate was 80%, with 3 patients achieving complete remission (CR), 4 patients achieving marrow CR, 4 patients achieving marrow CR with hematologic improvement, and one patient demonstrating hematologic improvement of erythrocytes. Median overall survival was not reached with median follow up of 13.8 months. Pembrolizumab with azacitidine should be further investigated in MDS.

Poly(ADP-ribose) polymerase (PARP) inhibitors are utilized in a range of solid tumor cancers. There are emerging concerns of PARP inhibitors with increased risk of developing MDS and acute myeloid leukemia (AML). A meta-analysis of 28 randomized control trials (RCT) with PARP inhibitors was done to evaluate risk of developing MDS and AML. Based on 18 RCTs with placebo control, PARP inhibitors increased risk of MDS and AML compared to placebo (Peto OR 2.63, p=0.026).  There was increased incidence of MDS and AML in the PARP inhibitor group compared to placebo (0.73% vs 0.47%). The median treatment duration was 9.8 months and median latency period since first exposure to a PARP inhibitor was 17.8 months. Use of PARP inhibitors is associated with increased risk of development of MDS and AML, and patients should be monitored accordingly.

All patients receiving active cancer treatment should receive a COVID-19 vaccine and should be prioritized for vaccination, according to preliminary recommendations from the National Comprehensive Cancer Network (NCCN).

Vaccination timing considerations vary based on factors such as cancer and treatment type, and reasons for delaying vaccination in the general public also apply to cancer patients (recent COVID-19 exposure, for example).

In general, however, patients with cancer should be assigned to Centers for Disease Control and Prevention priority group 1 b/c and immunized when vaccination is available to them, the guidelines state. Exceptions to this recommendation include:

• Patients undergoing hematopoietic stem cell transplant or receiving engineered cellular therapy such as chimeric antigen receptor T-cell therapy. Vaccination should be delayed for at least 3 months in these patients to maximize vaccine efficacy. Caregivers of these patients, however, should be immunized when possible.
• Patients with hematologic malignancies who are receiving intensive cytotoxic chemotherapy, such as cytarabine- or anthracycline-based regimens for acute myeloid leukemia. Vaccination in these patients should be delayed until absolute neutrophil count recovery.
• Patients undergoing major surgery. Vaccination should occur at least a few days before or after surgery.
• Patients who have experienced a severe or immediate adverse reaction to any of the ingredients in the mRNA COVID-19 vaccines.

Conversely, vaccination should occur when available in patients with hematologic malignancies and marrow failure who are expected to have limited or no recovery, patients with hematologic malignancies who are on long-term maintenance therapy, and patients with solid tumors who are receiving cytotoxic chemotherapy, targeted therapy, checkpoint inhibitors and other immunotherapy, or radiotherapy.

Caregivers, household contacts, and other close contacts who are 16 years of age and older should be vaccinated whenever they are eligible.
 

Unique concerns in patients with cancer

The NCCN recommendations were developed to address the unique issues and concerns with respect to patients with cancer, who have an increased risk of severe illness from SARS-CoV-2 infection. But the guidelines come with a caveat: “[t]here are limited safety and efficacy data in these patients,” the NCCN emphasized in a press statement.

“Right now, there is urgent need and limited data,” Steven Pergam, MD, co-leader of the NCCN COVID-19 Vaccination Committee, said in the statement.

“Our number one goal is helping to get the vaccine to as many people as we can,” Dr. Pergam said. “That means following existing national and regional directions for prioritizing people who are more likely to face death or severe illness from COVID-19.”

Dr. Pergam, associate professor at Fred Hutchinson Cancer Research Center in Seattle, further explained that “people receiving active cancer treatment are at greater risk for worse outcomes from COVID-19, particularly if they are older and have additional comorbidities, like immunosuppression.”

NCCN’s recommendations couldn’t have come at a better time for patients with cancer, according to Nora Disis, MD, a professor at the University of Washington in Seattle.

“The NCCN’s recommendations to prioritize COVID vaccinations for cancer patients on active treatment is an important step forward in protecting our patients from the infection,” Dr. Disis said in an interview.

“Cancer patients may be at higher risk for the complications seen with infection. In addition, cancer is a disease of older people, and a good number of our patients have the comorbidities that would predict a poorer outcome if they should become sick,” Dr. Disis added. “With the correct treatment, many patients with cancer will be long-term survivors. It is important that they be protected from infection with COVID to realize their best outcome.”
 

Additional vaccine considerations

The NCCN recommendations also address several other issues of importance for cancer patients, including:

• Deprioritizing other vaccines. COVID-19 vaccines should take precedence over other vaccines because data on dual vaccination are lacking. The NCCN recommends waiting 14 days after COVID-19 vaccination to deliver other vaccines.
• Vaccinating clinical trial participants. Trial leads should be consulted to prevent protocol violations or exclusions.
• Decision-making in the setting of limited vaccine availability. The NCCN noted that decisions on allocation must be made in accordance with state and local vaccine guidance but suggests prioritizing appropriate patients on active treatment, those planning to start treatment, and those who have just completed treatment. Additional risk factors for these patients, as well as other factors associated with risk for adverse COVID-19 outcomes, should also be considered. These include advanced age, comorbidities, and adverse social and demographic factors such as poverty and limited health care access.
• The need for ongoing prevention measures. Vaccines have been shown to decrease the incidence of COVID-19 and related complications, but it remains unclear whether vaccines prevent infection and subsequent transmission. This means everyone should continue following prevention recommendations, such as wearing masks and avoiding crowds.

The NCCN stressed that these recommendations are “intended to be a living document that is constantly evolving – it will be updated rapidly whenever new data comes out, as well as any potential new vaccines that may get approved in the future.” The NCCN also noted that the advisory committee will meet regularly to refine the recommendations as needed.

Dr. Pergam disclosed relationships with Chimerix Inc., Merck & Co., Global Life Technologies Inc., and Sanofi-Aventis. Dr. Disis disclosed grants from Pfizer, Bavarian Nordisk, Janssen, and Precigen. She is the founder of EpiThany and editor-in-chief of JAMA Oncology.

[email protected]

All patients receiving active cancer treatment should receive a COVID-19 vaccine and should be prioritized for vaccination, according to preliminary recommendations from the National Comprehensive Cancer Network (NCCN).

Vaccination timing considerations vary based on factors such as cancer and treatment type, and reasons for delaying vaccination in the general public also apply to cancer patients (recent COVID-19 exposure, for example).

In general, however, patients with cancer should be assigned to Centers for Disease Control and Prevention priority group 1 b/c and immunized when vaccination is available to them, the guidelines state. Exceptions to this recommendation include:

• Patients undergoing hematopoietic stem cell transplant or receiving engineered cellular therapy such as chimeric antigen receptor T-cell therapy. Vaccination should be delayed for at least 3 months in these patients to maximize vaccine efficacy. Caregivers of these patients, however, should be immunized when possible.
• Patients with hematologic malignancies who are receiving intensive cytotoxic chemotherapy, such as cytarabine- or anthracycline-based regimens for acute myeloid leukemia. Vaccination in these patients should be delayed until absolute neutrophil count recovery.
• Patients undergoing major surgery. Vaccination should occur at least a few days before or after surgery.
• Patients who have experienced a severe or immediate adverse reaction to any of the ingredients in the mRNA COVID-19 vaccines.

Conversely, vaccination should occur when available in patients with hematologic malignancies and marrow failure who are expected to have limited or no recovery, patients with hematologic malignancies who are on long-term maintenance therapy, and patients with solid tumors who are receiving cytotoxic chemotherapy, targeted therapy, checkpoint inhibitors and other immunotherapy, or radiotherapy.

Caregivers, household contacts, and other close contacts who are 16 years of age and older should be vaccinated whenever they are eligible.
 

Unique concerns in patients with cancer

The NCCN recommendations were developed to address the unique issues and concerns with respect to patients with cancer, who have an increased risk of severe illness from SARS-CoV-2 infection. But the guidelines come with a caveat: “[t]here are limited safety and efficacy data in these patients,” the NCCN emphasized in a press statement.

“Right now, there is urgent need and limited data,” Steven Pergam, MD, co-leader of the NCCN COVID-19 Vaccination Committee, said in the statement.

“Our number one goal is helping to get the vaccine to as many people as we can,” Dr. Pergam said. “That means following existing national and regional directions for prioritizing people who are more likely to face death or severe illness from COVID-19.”

Dr. Pergam, associate professor at Fred Hutchinson Cancer Research Center in Seattle, further explained that “people receiving active cancer treatment are at greater risk for worse outcomes from COVID-19, particularly if they are older and have additional comorbidities, like immunosuppression.”

NCCN’s recommendations couldn’t have come at a better time for patients with cancer, according to Nora Disis, MD, a professor at the University of Washington in Seattle.

“The NCCN’s recommendations to prioritize COVID vaccinations for cancer patients on active treatment is an important step forward in protecting our patients from the infection,” Dr. Disis said in an interview.

“Cancer patients may be at higher risk for the complications seen with infection. In addition, cancer is a disease of older people, and a good number of our patients have the comorbidities that would predict a poorer outcome if they should become sick,” Dr. Disis added. “With the correct treatment, many patients with cancer will be long-term survivors. It is important that they be protected from infection with COVID to realize their best outcome.”
 

Additional vaccine considerations

The NCCN recommendations also address several other issues of importance for cancer patients, including:

• Deprioritizing other vaccines. COVID-19 vaccines should take precedence over other vaccines because data on dual vaccination are lacking. The NCCN recommends waiting 14 days after COVID-19 vaccination to deliver other vaccines.
• Vaccinating clinical trial participants. Trial leads should be consulted to prevent protocol violations or exclusions.
• Decision-making in the setting of limited vaccine availability. The NCCN noted that decisions on allocation must be made in accordance with state and local vaccine guidance but suggests prioritizing appropriate patients on active treatment, those planning to start treatment, and those who have just completed treatment. Additional risk factors for these patients, as well as other factors associated with risk for adverse COVID-19 outcomes, should also be considered. These include advanced age, comorbidities, and adverse social and demographic factors such as poverty and limited health care access.
• The need for ongoing prevention measures. Vaccines have been shown to decrease the incidence of COVID-19 and related complications, but it remains unclear whether vaccines prevent infection and subsequent transmission. This means everyone should continue following prevention recommendations, such as wearing masks and avoiding crowds.

The NCCN stressed that these recommendations are “intended to be a living document that is constantly evolving – it will be updated rapidly whenever new data comes out, as well as any potential new vaccines that may get approved in the future.” The NCCN also noted that the advisory committee will meet regularly to refine the recommendations as needed.

Dr. Pergam disclosed relationships with Chimerix Inc., Merck & Co., Global Life Technologies Inc., and Sanofi-Aventis. Dr. Disis disclosed grants from Pfizer, Bavarian Nordisk, Janssen, and Precigen. She is the founder of EpiThany and editor-in-chief of JAMA Oncology.

[email protected]

All patients receiving active cancer treatment should receive a COVID-19 vaccine and should be prioritized for vaccination, according to preliminary recommendations from the National Comprehensive Cancer Network (NCCN).

Vaccination timing considerations vary based on factors such as cancer and treatment type, and reasons for delaying vaccination in the general public also apply to cancer patients (recent COVID-19 exposure, for example).

In general, however, patients with cancer should be assigned to Centers for Disease Control and Prevention priority group 1 b/c and immunized when vaccination is available to them, the guidelines state. Exceptions to this recommendation include:

• Patients undergoing hematopoietic stem cell transplant or receiving engineered cellular therapy such as chimeric antigen receptor T-cell therapy. Vaccination should be delayed for at least 3 months in these patients to maximize vaccine efficacy. Caregivers of these patients, however, should be immunized when possible.
• Patients with hematologic malignancies who are receiving intensive cytotoxic chemotherapy, such as cytarabine- or anthracycline-based regimens for acute myeloid leukemia. Vaccination in these patients should be delayed until absolute neutrophil count recovery.
• Patients undergoing major surgery. Vaccination should occur at least a few days before or after surgery.
• Patients who have experienced a severe or immediate adverse reaction to any of the ingredients in the mRNA COVID-19 vaccines.

Conversely, vaccination should occur when available in patients with hematologic malignancies and marrow failure who are expected to have limited or no recovery, patients with hematologic malignancies who are on long-term maintenance therapy, and patients with solid tumors who are receiving cytotoxic chemotherapy, targeted therapy, checkpoint inhibitors and other immunotherapy, or radiotherapy.

Caregivers, household contacts, and other close contacts who are 16 years of age and older should be vaccinated whenever they are eligible.
 

Unique concerns in patients with cancer

The NCCN recommendations were developed to address the unique issues and concerns with respect to patients with cancer, who have an increased risk of severe illness from SARS-CoV-2 infection. But the guidelines come with a caveat: “[t]here are limited safety and efficacy data in these patients,” the NCCN emphasized in a press statement.

“Right now, there is urgent need and limited data,” Steven Pergam, MD, co-leader of the NCCN COVID-19 Vaccination Committee, said in the statement.

“Our number one goal is helping to get the vaccine to as many people as we can,” Dr. Pergam said. “That means following existing national and regional directions for prioritizing people who are more likely to face death or severe illness from COVID-19.”

Dr. Pergam, associate professor at Fred Hutchinson Cancer Research Center in Seattle, further explained that “people receiving active cancer treatment are at greater risk for worse outcomes from COVID-19, particularly if they are older and have additional comorbidities, like immunosuppression.”

NCCN’s recommendations couldn’t have come at a better time for patients with cancer, according to Nora Disis, MD, a professor at the University of Washington in Seattle.

“The NCCN’s recommendations to prioritize COVID vaccinations for cancer patients on active treatment is an important step forward in protecting our patients from the infection,” Dr. Disis said in an interview.

“Cancer patients may be at higher risk for the complications seen with infection. In addition, cancer is a disease of older people, and a good number of our patients have the comorbidities that would predict a poorer outcome if they should become sick,” Dr. Disis added. “With the correct treatment, many patients with cancer will be long-term survivors. It is important that they be protected from infection with COVID to realize their best outcome.”
 

Additional vaccine considerations

The NCCN recommendations also address several other issues of importance for cancer patients, including:

• Deprioritizing other vaccines. COVID-19 vaccines should take precedence over other vaccines because data on dual vaccination are lacking. The NCCN recommends waiting 14 days after COVID-19 vaccination to deliver other vaccines.
• Vaccinating clinical trial participants. Trial leads should be consulted to prevent protocol violations or exclusions.
• Decision-making in the setting of limited vaccine availability. The NCCN noted that decisions on allocation must be made in accordance with state and local vaccine guidance but suggests prioritizing appropriate patients on active treatment, those planning to start treatment, and those who have just completed treatment. Additional risk factors for these patients, as well as other factors associated with risk for adverse COVID-19 outcomes, should also be considered. These include advanced age, comorbidities, and adverse social and demographic factors such as poverty and limited health care access.
• The need for ongoing prevention measures. Vaccines have been shown to decrease the incidence of COVID-19 and related complications, but it remains unclear whether vaccines prevent infection and subsequent transmission. This means everyone should continue following prevention recommendations, such as wearing masks and avoiding crowds.

The NCCN stressed that these recommendations are “intended to be a living document that is constantly evolving – it will be updated rapidly whenever new data comes out, as well as any potential new vaccines that may get approved in the future.” The NCCN also noted that the advisory committee will meet regularly to refine the recommendations as needed.

Dr. Pergam disclosed relationships with Chimerix Inc., Merck & Co., Global Life Technologies Inc., and Sanofi-Aventis. Dr. Disis disclosed grants from Pfizer, Bavarian Nordisk, Janssen, and Precigen. She is the founder of EpiThany and editor-in-chief of JAMA Oncology.

[email protected]

COVID-19 infection altered the gut microbiota of adult patients and caused depletion of several types of bacteria with known immunomodulatory properties, based on data from a cohort study of 100 patients with confirmed COVID-19 infections from two hospitals.

“As the GI tract is the largest immunological organ in the body and its resident microbiota are known to modulate host immune responses, we hypothesized that the gut microbiota is associated with host inflammatory immune responses in COVID19,” wrote Yun Kit Yeoh, PhD, of the Chinese University of Hong Kong, and colleagues.

In a study published in Gut, the researchers investigated patient microbiota by collecting blood, stool, and patient records between February and May 2020 from 100 confirmed SARS-CoV-2–infected patients in Hong Kong during hospitalization, as well as follow-up stool samples from 27 patients up to 30 days after they cleared the COVID-19 virus; these observations were compared with 78 non–COVID-19 controls.

Overall, 274 stool samples were sequenced. Samples collected from patients during hospitalization for COVID-19 were compared with non–COVID-19 controls. The presence of phylum Bacteroidetes was significantly higher in COVID-19 patients compared with controls (23.9% vs. 12.8%; P < .001), as were Actinobacteria (26.1% vs. 19.0%; P < .001).

After controlling for antibiotics, the investigators found that “differences between cohorts were primarily linked to enrichment of taxa such as Parabacteroides, Sutterella wadsworthensis, and Bacteroides caccae and depletion of Adlercreutzia equolifaciens, Dorea formicigenerans, and Clostridium leptum in COVID-19 relative to non-COVID-19” (P < .05). In addition, Faecalibacterium prausnitzii and Bifidobacterium bifidum were negatively correlated with COVID-19 severity after investigators controlled for patient age and antibiotic use (P < .05).

The researchers also examined bacteria in COVID-19 patients and controls in the context of cytokines and other inflammatory markers. “We hypothesized that these compositional changes play a role in exacerbating disease by contributing to dysregulation of the immune response,” they said.

In fact, species depleted in COVID-19 patients including included B. adolescentis, E. rectale, and F. prausnitzii were negatively correlated with inflammatory markers including CXCL10, IL-10, TNF-alpha, and CCL2.

In addition, 42 stool samples from 27 patients showed significantly distinct gut microbiota from controls up to 30 days (median, 6 days) after virus clearance, regardless of antibiotics use (P < .05), the researchers said.
 

Long-term data needed

The study findings were limited by several factors, including the potential confounding of microbial signatures associated with COVID-19 because of heterogeneous patient management in the clinical setting and the potential that gut microbiota reflects a patient’s health with no impact on disease severity, as well as lack of data on the role of antibiotics for severe and critical patients, the researchers noted. In addition, “gut microbiota composition is highly heterogeneous across human populations and changes in compositions reported here may not necessarily be reflected in patients with COVID-19 from other biogeographies,” they wrote.

The “longer follow-up of patients with COVID-19 (e.g., 3 months to 1 year after clearing the virus) is needed to address questions related to the duration of gut microbiota dysbiosis post recovery, link between microbiota dysbiosis and long-term persistent symptoms, and whether the dysbiosis or enrichment/depletion of specific gut microorganisms predisposes recovered individuals to future health problems,” they wrote.

However, the results suggest a likely role for gut microorganisms in host inflammatory responses to COVID-19 infection, and “underscore an urgent need to understand the specific roles of gut microorganisms in human immune function and systemic inflammation,” they concluded.
 

More than infectious

“A growing body of evidence suggests that severity of illness from COVID-19 is largely determined by the patient’s aberrant immune response to the virus,” Jatin Roper, MD, of Duke University, Durham, N.C., said in an interview. “Therefore, a critical question is: What patient factors determine this immune response? The gut microbiota closely interact with the host immune system and are altered in many immunological diseases,” he said. “Furthermore, the SARS-CoV-2 virus infects enterocytes in the intestine and causes symptomatic gastrointestinal disease in a subset of patients. Therefore, understanding a possible association between gut microbiota and COVID-19 may reveal microbial species involved in disease pathogenesis,” he emphasized.   

In the current study, “I was surprised to find that COVID-19 infection is associated with depletion of immunomodulatory gut bacteria,” said Dr. Roper. “An open question is whether these changes are caused by the SARS-CoV-2 virus and then result in altered immune response. Alternatively, the changes in gut microbiota may be a result of the immune response or other changes associated with the disease,” he said.

“COVID-19 is an immunological disease, not just an infectious disease,” explained Dr. Roper. “The gut microbiota may play an important role in the pathogenesis of the disease. Thus, specific gut microbes could one day be analyzed to risk stratify patients, or even modified to treat the disease,” he noted.
 

Beyond COVID-19

“Given the impact of the gut microbiota on health and disease, as well as the impact of diseases on the microbiota, I am not at all surprised to find that there were significant changes in the microbiota of COVID-19 patients and that these changes are associated with inflammatory cytokines, chemokines, and blood markers of tissue damage,” said Anthony Sung, MD, also of Duke University.

According to Dr. Sung, researchers have already been investigating possible connections between gut microbiota and other conditions such as Alzheimer’s disease, and it’s been hypothesized that these connections are mediated by interactions between the gut microbiota and the immune system.

“While this is an important paper in our understanding of COVID-19, and highlights the microbiome as a potential therapeutic target, we need to conduct clinical trials of microbiota-based interventions before we can fully realize the clinical implications of these findings,” he said.

The study was supported by the Health and Medical Research Fund, the Food and Health Bureau, The Government of the Hong Kong Special Administrative Region, and donations from Hui Hoy & Chow Sin Lan Charity Fund Limited, Pine and Crane Company Limited, Mr. Hui Ming, and The D.H. Chen Foundation. The researchers had no financial conflicts to disclose. Dr. Roper and Dr. Sung had no financial conflicts to disclose.

For the latest clinical guidance, education, research and physician resources about coronavirus, visit the AGA COVID-19 Resource Center at www.gastro.org/COVID.

COVID-19 infection altered the gut microbiota of adult patients and caused depletion of several types of bacteria with known immunomodulatory properties, based on data from a cohort study of 100 patients with confirmed COVID-19 infections from two hospitals.

“As the GI tract is the largest immunological organ in the body and its resident microbiota are known to modulate host immune responses, we hypothesized that the gut microbiota is associated with host inflammatory immune responses in COVID19,” wrote Yun Kit Yeoh, PhD, of the Chinese University of Hong Kong, and colleagues.

In a study published in Gut, the researchers investigated patient microbiota by collecting blood, stool, and patient records between February and May 2020 from 100 confirmed SARS-CoV-2–infected patients in Hong Kong during hospitalization, as well as follow-up stool samples from 27 patients up to 30 days after they cleared the COVID-19 virus; these observations were compared with 78 non–COVID-19 controls.

Overall, 274 stool samples were sequenced. Samples collected from patients during hospitalization for COVID-19 were compared with non–COVID-19 controls. The presence of phylum Bacteroidetes was significantly higher in COVID-19 patients compared with controls (23.9% vs. 12.8%; P < .001), as were Actinobacteria (26.1% vs. 19.0%; P < .001).

After controlling for antibiotics, the investigators found that “differences between cohorts were primarily linked to enrichment of taxa such as Parabacteroides, Sutterella wadsworthensis, and Bacteroides caccae and depletion of Adlercreutzia equolifaciens, Dorea formicigenerans, and Clostridium leptum in COVID-19 relative to non-COVID-19” (P < .05). In addition, Faecalibacterium prausnitzii and Bifidobacterium bifidum were negatively correlated with COVID-19 severity after investigators controlled for patient age and antibiotic use (P < .05).

The researchers also examined bacteria in COVID-19 patients and controls in the context of cytokines and other inflammatory markers. “We hypothesized that these compositional changes play a role in exacerbating disease by contributing to dysregulation of the immune response,” they said.

In fact, species depleted in COVID-19 patients including included B. adolescentis, E. rectale, and F. prausnitzii were negatively correlated with inflammatory markers including CXCL10, IL-10, TNF-alpha, and CCL2.

In addition, 42 stool samples from 27 patients showed significantly distinct gut microbiota from controls up to 30 days (median, 6 days) after virus clearance, regardless of antibiotics use (P < .05), the researchers said.
 

Long-term data needed

The study findings were limited by several factors, including the potential confounding of microbial signatures associated with COVID-19 because of heterogeneous patient management in the clinical setting and the potential that gut microbiota reflects a patient’s health with no impact on disease severity, as well as lack of data on the role of antibiotics for severe and critical patients, the researchers noted. In addition, “gut microbiota composition is highly heterogeneous across human populations and changes in compositions reported here may not necessarily be reflected in patients with COVID-19 from other biogeographies,” they wrote.

The “longer follow-up of patients with COVID-19 (e.g., 3 months to 1 year after clearing the virus) is needed to address questions related to the duration of gut microbiota dysbiosis post recovery, link between microbiota dysbiosis and long-term persistent symptoms, and whether the dysbiosis or enrichment/depletion of specific gut microorganisms predisposes recovered individuals to future health problems,” they wrote.

However, the results suggest a likely role for gut microorganisms in host inflammatory responses to COVID-19 infection, and “underscore an urgent need to understand the specific roles of gut microorganisms in human immune function and systemic inflammation,” they concluded.
 

More than infectious

“A growing body of evidence suggests that severity of illness from COVID-19 is largely determined by the patient’s aberrant immune response to the virus,” Jatin Roper, MD, of Duke University, Durham, N.C., said in an interview. “Therefore, a critical question is: What patient factors determine this immune response? The gut microbiota closely interact with the host immune system and are altered in many immunological diseases,” he said. “Furthermore, the SARS-CoV-2 virus infects enterocytes in the intestine and causes symptomatic gastrointestinal disease in a subset of patients. Therefore, understanding a possible association between gut microbiota and COVID-19 may reveal microbial species involved in disease pathogenesis,” he emphasized.   

In the current study, “I was surprised to find that COVID-19 infection is associated with depletion of immunomodulatory gut bacteria,” said Dr. Roper. “An open question is whether these changes are caused by the SARS-CoV-2 virus and then result in altered immune response. Alternatively, the changes in gut microbiota may be a result of the immune response or other changes associated with the disease,” he said.

“COVID-19 is an immunological disease, not just an infectious disease,” explained Dr. Roper. “The gut microbiota may play an important role in the pathogenesis of the disease. Thus, specific gut microbes could one day be analyzed to risk stratify patients, or even modified to treat the disease,” he noted.
 

Beyond COVID-19

“Given the impact of the gut microbiota on health and disease, as well as the impact of diseases on the microbiota, I am not at all surprised to find that there were significant changes in the microbiota of COVID-19 patients and that these changes are associated with inflammatory cytokines, chemokines, and blood markers of tissue damage,” said Anthony Sung, MD, also of Duke University.

According to Dr. Sung, researchers have already been investigating possible connections between gut microbiota and other conditions such as Alzheimer’s disease, and it’s been hypothesized that these connections are mediated by interactions between the gut microbiota and the immune system.

“While this is an important paper in our understanding of COVID-19, and highlights the microbiome as a potential therapeutic target, we need to conduct clinical trials of microbiota-based interventions before we can fully realize the clinical implications of these findings,” he said.

The study was supported by the Health and Medical Research Fund, the Food and Health Bureau, The Government of the Hong Kong Special Administrative Region, and donations from Hui Hoy & Chow Sin Lan Charity Fund Limited, Pine and Crane Company Limited, Mr. Hui Ming, and The D.H. Chen Foundation. The researchers had no financial conflicts to disclose. Dr. Roper and Dr. Sung had no financial conflicts to disclose.

For the latest clinical guidance, education, research and physician resources about coronavirus, visit the AGA COVID-19 Resource Center at www.gastro.org/COVID.

COVID-19 infection altered the gut microbiota of adult patients and caused depletion of several types of bacteria with known immunomodulatory properties, based on data from a cohort study of 100 patients with confirmed COVID-19 infections from two hospitals.

“As the GI tract is the largest immunological organ in the body and its resident microbiota are known to modulate host immune responses, we hypothesized that the gut microbiota is associated with host inflammatory immune responses in COVID19,” wrote Yun Kit Yeoh, PhD, of the Chinese University of Hong Kong, and colleagues.

In a study published in Gut, the researchers investigated patient microbiota by collecting blood, stool, and patient records between February and May 2020 from 100 confirmed SARS-CoV-2–infected patients in Hong Kong during hospitalization, as well as follow-up stool samples from 27 patients up to 30 days after they cleared the COVID-19 virus; these observations were compared with 78 non–COVID-19 controls.

Overall, 274 stool samples were sequenced. Samples collected from patients during hospitalization for COVID-19 were compared with non–COVID-19 controls. The presence of phylum Bacteroidetes was significantly higher in COVID-19 patients compared with controls (23.9% vs. 12.8%; P < .001), as were Actinobacteria (26.1% vs. 19.0%; P < .001).

After controlling for antibiotics, the investigators found that “differences between cohorts were primarily linked to enrichment of taxa such as Parabacteroides, Sutterella wadsworthensis, and Bacteroides caccae and depletion of Adlercreutzia equolifaciens, Dorea formicigenerans, and Clostridium leptum in COVID-19 relative to non-COVID-19” (P < .05). In addition, Faecalibacterium prausnitzii and Bifidobacterium bifidum were negatively correlated with COVID-19 severity after investigators controlled for patient age and antibiotic use (P < .05).

The researchers also examined bacteria in COVID-19 patients and controls in the context of cytokines and other inflammatory markers. “We hypothesized that these compositional changes play a role in exacerbating disease by contributing to dysregulation of the immune response,” they said.

In fact, species depleted in COVID-19 patients including included B. adolescentis, E. rectale, and F. prausnitzii were negatively correlated with inflammatory markers including CXCL10, IL-10, TNF-alpha, and CCL2.

In addition, 42 stool samples from 27 patients showed significantly distinct gut microbiota from controls up to 30 days (median, 6 days) after virus clearance, regardless of antibiotics use (P < .05), the researchers said.
 

Long-term data needed

The study findings were limited by several factors, including the potential confounding of microbial signatures associated with COVID-19 because of heterogeneous patient management in the clinical setting and the potential that gut microbiota reflects a patient’s health with no impact on disease severity, as well as lack of data on the role of antibiotics for severe and critical patients, the researchers noted. In addition, “gut microbiota composition is highly heterogeneous across human populations and changes in compositions reported here may not necessarily be reflected in patients with COVID-19 from other biogeographies,” they wrote.

The “longer follow-up of patients with COVID-19 (e.g., 3 months to 1 year after clearing the virus) is needed to address questions related to the duration of gut microbiota dysbiosis post recovery, link between microbiota dysbiosis and long-term persistent symptoms, and whether the dysbiosis or enrichment/depletion of specific gut microorganisms predisposes recovered individuals to future health problems,” they wrote.

However, the results suggest a likely role for gut microorganisms in host inflammatory responses to COVID-19 infection, and “underscore an urgent need to understand the specific roles of gut microorganisms in human immune function and systemic inflammation,” they concluded.
 

More than infectious

“A growing body of evidence suggests that severity of illness from COVID-19 is largely determined by the patient’s aberrant immune response to the virus,” Jatin Roper, MD, of Duke University, Durham, N.C., said in an interview. “Therefore, a critical question is: What patient factors determine this immune response? The gut microbiota closely interact with the host immune system and are altered in many immunological diseases,” he said. “Furthermore, the SARS-CoV-2 virus infects enterocytes in the intestine and causes symptomatic gastrointestinal disease in a subset of patients. Therefore, understanding a possible association between gut microbiota and COVID-19 may reveal microbial species involved in disease pathogenesis,” he emphasized.   

In the current study, “I was surprised to find that COVID-19 infection is associated with depletion of immunomodulatory gut bacteria,” said Dr. Roper. “An open question is whether these changes are caused by the SARS-CoV-2 virus and then result in altered immune response. Alternatively, the changes in gut microbiota may be a result of the immune response or other changes associated with the disease,” he said.

“COVID-19 is an immunological disease, not just an infectious disease,” explained Dr. Roper. “The gut microbiota may play an important role in the pathogenesis of the disease. Thus, specific gut microbes could one day be analyzed to risk stratify patients, or even modified to treat the disease,” he noted.
 

Beyond COVID-19

“Given the impact of the gut microbiota on health and disease, as well as the impact of diseases on the microbiota, I am not at all surprised to find that there were significant changes in the microbiota of COVID-19 patients and that these changes are associated with inflammatory cytokines, chemokines, and blood markers of tissue damage,” said Anthony Sung, MD, also of Duke University.

According to Dr. Sung, researchers have already been investigating possible connections between gut microbiota and other conditions such as Alzheimer’s disease, and it’s been hypothesized that these connections are mediated by interactions between the gut microbiota and the immune system.

“While this is an important paper in our understanding of COVID-19, and highlights the microbiome as a potential therapeutic target, we need to conduct clinical trials of microbiota-based interventions before we can fully realize the clinical implications of these findings,” he said.

The study was supported by the Health and Medical Research Fund, the Food and Health Bureau, The Government of the Hong Kong Special Administrative Region, and donations from Hui Hoy & Chow Sin Lan Charity Fund Limited, Pine and Crane Company Limited, Mr. Hui Ming, and The D.H. Chen Foundation. The researchers had no financial conflicts to disclose. Dr. Roper and Dr. Sung had no financial conflicts to disclose.

For the latest clinical guidance, education, research and physician resources about coronavirus, visit the AGA COVID-19 Resource Center at www.gastro.org/COVID.

Patients with an implantable cardioverter defibrillator (ICD) should be warned that some newer models of smartphones equipped with magnets, such as the iPhone 12, can disable their device, inhibiting its lifesaving functions, according to investigators who tested and confirmed this effect.

SL/Getty Images

“Once the iPhone was brought close to the ICD over the left chest area, immediate suspension of ICD therapies was noted which persisted for the duration of the test,” reported the investigating team led by Joshua C. Greenberg, MD, who is an electrophysiology fellow at Henry Ford Hospital, Detroit. The results were published in Heart Rhythm.

The American Heart Association has already cautioned that magnetic fields can inhibit the pulse generators for ICDs and pacemakers. On the AHA website, there is a list of devices and their potential for functional interference, but cell phones and other common devices are identified as posing a low risk.

The most recent iPhone and perhaps other advanced smartphones appear to be different. According to the authors of a study that tested the iPhone 12, this model has a circular array of magnets around a central charging coil. This array interacts with Apple’s proprietary MagSafe technology, which accelerates charging. The magnets also serve to orient the phone on the charger and enable other MagSafe accessories.

The authors of the new study were concerned that this array of magnets might be sufficiently strong to interfere with ICDs or other devices at risk. In a previously published study, the strength of a magnetic field sufficient to interfere with implantable cardiac devices was estimated to be at least 10 gauss.

Tests were performed on a patient wearing a Medtronic ICD.

“Once the iPhone was brought close to the ICD over the left chest area, immediate suspension of ICD therapies was noted,” according to the authors of the study. The functional loss of the ICS persisted for the duration of proximity. It was reproduced multiple times and with multiple phone positions.

Previous studies have provided evidence that earlier models do not share this risk. In a study testing the iPhone 6 and an Apple Watch in 148 patients with various types of implantable electronic devices, including pacemakers, cardioverter defibrillators, resynchronization defibrillators, and resynchronization pacemakers, only one instance of interference was observed in 1,352 tests.

With wand telemetry, iPhone-induced interferences could be detected with the iPhone 6 in 14% of the patients, but these did not appear to be clinically meaningful, and this type of interference could not be detected with the Apple Watch, according to the report. The single observed interaction, which was between an iPhone 6 and a dual-chamber pacemaker, suggested device-device interactions are uncommon.

More recently, a woman with a single-chamber Medtronic ICD who went to sleep wearing an Apple Watch was awoken by warning beeps from her cardiac device, according to a case report published online. The Apple watch became the prime suspect in causing the ICD warning when proximity of the watch reproduced the warning during clinical examination. However, the magnetic interference was ultimately found to be emanating from the wristband, not the watch.

This case prompted additional studies with Fitbit and other Apple Watch wristbands. Both wristbands contain magnets used to track heart rate. Both were found capable of deactivating ICDs at distances of approximately 2 cm. On the basis of these results, the authors concluded that patients should be counseled about the risk posed by wristbands used in fitness tracking, concluding that they should be kept at least 6 inches away from ICDs and not worn while sleeping.

On their website, Apple maintains a page that specifically warns about the potential for interactions between iPhone 12s and medical devices . Although there is an acknowledgment that the iPhone12 contains more magnets than prior iPhone models, it is stated that iPhone 12 models are “not expected to pose a greater risk of magnetic interference to medical devices than prior iPhone models.” Nevertheless, the Apple instructions advise keeping the iPhone and MagSafe accessories more than 6 inches away from medical devices.

Dr. Greenberg and coinvestigators concluded that the iPhone 12 does pose a greater risk to the dysfunction of ICDs and other medical devices because of the more powerful magnets. As a result, the study brings forward “an important public health issue concerning the newer generation iPhone 12.”

Well aware of this issue and this study, Bruce L. Wilkoff, MD, director of cardiac pacing and tachyarrhythmia devices, Cleveland Clinic, agreed. He said the focus should not be restricted to the iPhone 12 series but other wearable devices as alluded to in the study.

“Pacemakers and implantable defibrillators are designed to respond to magnets for important reasons, but magnets have many common uses,” he said. These can change the function of the implantable cardiac devise, but “it is temporary and only when placed in close proximity.”

The solution is simple. “Patients should be careful to avoid locating these objects near these devices,” Dr. Wilkoff said.

However, the first step is awareness. According to the study authors, devices with magnets powerful enough to impair function of implantable devices, such as the iPhone 12 “can potentially inhibit lifesaving therapy.”

Patients should be counseled and provided with practical steps, according to the authors. This includes keeping these devices out of pockets near implantable devices. They called for more noise from makers of smartphones and other devices with strong enough magnets to alter pacemaker and ICD function, and they advised physicians to draw awareness to this issue.

Dr. Greenberg reported no potential conflicts of interest.

Patients with an implantable cardioverter defibrillator (ICD) should be warned that some newer models of smartphones equipped with magnets, such as the iPhone 12, can disable their device, inhibiting its lifesaving functions, according to investigators who tested and confirmed this effect.

SL/Getty Images

“Once the iPhone was brought close to the ICD over the left chest area, immediate suspension of ICD therapies was noted which persisted for the duration of the test,” reported the investigating team led by Joshua C. Greenberg, MD, who is an electrophysiology fellow at Henry Ford Hospital, Detroit. The results were published in Heart Rhythm.

The American Heart Association has already cautioned that magnetic fields can inhibit the pulse generators for ICDs and pacemakers. On the AHA website, there is a list of devices and their potential for functional interference, but cell phones and other common devices are identified as posing a low risk.

The most recent iPhone and perhaps other advanced smartphones appear to be different. According to the authors of a study that tested the iPhone 12, this model has a circular array of magnets around a central charging coil. This array interacts with Apple’s proprietary MagSafe technology, which accelerates charging. The magnets also serve to orient the phone on the charger and enable other MagSafe accessories.

The authors of the new study were concerned that this array of magnets might be sufficiently strong to interfere with ICDs or other devices at risk. In a previously published study, the strength of a magnetic field sufficient to interfere with implantable cardiac devices was estimated to be at least 10 gauss.

Tests were performed on a patient wearing a Medtronic ICD.

“Once the iPhone was brought close to the ICD over the left chest area, immediate suspension of ICD therapies was noted,” according to the authors of the study. The functional loss of the ICS persisted for the duration of proximity. It was reproduced multiple times and with multiple phone positions.

Previous studies have provided evidence that earlier models do not share this risk. In a study testing the iPhone 6 and an Apple Watch in 148 patients with various types of implantable electronic devices, including pacemakers, cardioverter defibrillators, resynchronization defibrillators, and resynchronization pacemakers, only one instance of interference was observed in 1,352 tests.

With wand telemetry, iPhone-induced interferences could be detected with the iPhone 6 in 14% of the patients, but these did not appear to be clinically meaningful, and this type of interference could not be detected with the Apple Watch, according to the report. The single observed interaction, which was between an iPhone 6 and a dual-chamber pacemaker, suggested device-device interactions are uncommon.

More recently, a woman with a single-chamber Medtronic ICD who went to sleep wearing an Apple Watch was awoken by warning beeps from her cardiac device, according to a case report published online. The Apple watch became the prime suspect in causing the ICD warning when proximity of the watch reproduced the warning during clinical examination. However, the magnetic interference was ultimately found to be emanating from the wristband, not the watch.

This case prompted additional studies with Fitbit and other Apple Watch wristbands. Both wristbands contain magnets used to track heart rate. Both were found capable of deactivating ICDs at distances of approximately 2 cm. On the basis of these results, the authors concluded that patients should be counseled about the risk posed by wristbands used in fitness tracking, concluding that they should be kept at least 6 inches away from ICDs and not worn while sleeping.

On their website, Apple maintains a page that specifically warns about the potential for interactions between iPhone 12s and medical devices . Although there is an acknowledgment that the iPhone12 contains more magnets than prior iPhone models, it is stated that iPhone 12 models are “not expected to pose a greater risk of magnetic interference to medical devices than prior iPhone models.” Nevertheless, the Apple instructions advise keeping the iPhone and MagSafe accessories more than 6 inches away from medical devices.

Dr. Greenberg and coinvestigators concluded that the iPhone 12 does pose a greater risk to the dysfunction of ICDs and other medical devices because of the more powerful magnets. As a result, the study brings forward “an important public health issue concerning the newer generation iPhone 12.”

Well aware of this issue and this study, Bruce L. Wilkoff, MD, director of cardiac pacing and tachyarrhythmia devices, Cleveland Clinic, agreed. He said the focus should not be restricted to the iPhone 12 series but other wearable devices as alluded to in the study.

“Pacemakers and implantable defibrillators are designed to respond to magnets for important reasons, but magnets have many common uses,” he said. These can change the function of the implantable cardiac devise, but “it is temporary and only when placed in close proximity.”

The solution is simple. “Patients should be careful to avoid locating these objects near these devices,” Dr. Wilkoff said.

However, the first step is awareness. According to the study authors, devices with magnets powerful enough to impair function of implantable devices, such as the iPhone 12 “can potentially inhibit lifesaving therapy.”

Patients should be counseled and provided with practical steps, according to the authors. This includes keeping these devices out of pockets near implantable devices. They called for more noise from makers of smartphones and other devices with strong enough magnets to alter pacemaker and ICD function, and they advised physicians to draw awareness to this issue.

Dr. Greenberg reported no potential conflicts of interest.

Patients with an implantable cardioverter defibrillator (ICD) should be warned that some newer models of smartphones equipped with magnets, such as the iPhone 12, can disable their device, inhibiting its lifesaving functions, according to investigators who tested and confirmed this effect.

SL/Getty Images

“Once the iPhone was brought close to the ICD over the left chest area, immediate suspension of ICD therapies was noted which persisted for the duration of the test,” reported the investigating team led by Joshua C. Greenberg, MD, who is an electrophysiology fellow at Henry Ford Hospital, Detroit. The results were published in Heart Rhythm.

The American Heart Association has already cautioned that magnetic fields can inhibit the pulse generators for ICDs and pacemakers. On the AHA website, there is a list of devices and their potential for functional interference, but cell phones and other common devices are identified as posing a low risk.

The most recent iPhone and perhaps other advanced smartphones appear to be different. According to the authors of a study that tested the iPhone 12, this model has a circular array of magnets around a central charging coil. This array interacts with Apple’s proprietary MagSafe technology, which accelerates charging. The magnets also serve to orient the phone on the charger and enable other MagSafe accessories.

The authors of the new study were concerned that this array of magnets might be sufficiently strong to interfere with ICDs or other devices at risk. In a previously published study, the strength of a magnetic field sufficient to interfere with implantable cardiac devices was estimated to be at least 10 gauss.

Tests were performed on a patient wearing a Medtronic ICD.

“Once the iPhone was brought close to the ICD over the left chest area, immediate suspension of ICD therapies was noted,” according to the authors of the study. The functional loss of the ICS persisted for the duration of proximity. It was reproduced multiple times and with multiple phone positions.

Previous studies have provided evidence that earlier models do not share this risk. In a study testing the iPhone 6 and an Apple Watch in 148 patients with various types of implantable electronic devices, including pacemakers, cardioverter defibrillators, resynchronization defibrillators, and resynchronization pacemakers, only one instance of interference was observed in 1,352 tests.

With wand telemetry, iPhone-induced interferences could be detected with the iPhone 6 in 14% of the patients, but these did not appear to be clinically meaningful, and this type of interference could not be detected with the Apple Watch, according to the report. The single observed interaction, which was between an iPhone 6 and a dual-chamber pacemaker, suggested device-device interactions are uncommon.

More recently, a woman with a single-chamber Medtronic ICD who went to sleep wearing an Apple Watch was awoken by warning beeps from her cardiac device, according to a case report published online. The Apple watch became the prime suspect in causing the ICD warning when proximity of the watch reproduced the warning during clinical examination. However, the magnetic interference was ultimately found to be emanating from the wristband, not the watch.

This case prompted additional studies with Fitbit and other Apple Watch wristbands. Both wristbands contain magnets used to track heart rate. Both were found capable of deactivating ICDs at distances of approximately 2 cm. On the basis of these results, the authors concluded that patients should be counseled about the risk posed by wristbands used in fitness tracking, concluding that they should be kept at least 6 inches away from ICDs and not worn while sleeping.

On their website, Apple maintains a page that specifically warns about the potential for interactions between iPhone 12s and medical devices . Although there is an acknowledgment that the iPhone12 contains more magnets than prior iPhone models, it is stated that iPhone 12 models are “not expected to pose a greater risk of magnetic interference to medical devices than prior iPhone models.” Nevertheless, the Apple instructions advise keeping the iPhone and MagSafe accessories more than 6 inches away from medical devices.

Dr. Greenberg and coinvestigators concluded that the iPhone 12 does pose a greater risk to the dysfunction of ICDs and other medical devices because of the more powerful magnets. As a result, the study brings forward “an important public health issue concerning the newer generation iPhone 12.”

Well aware of this issue and this study, Bruce L. Wilkoff, MD, director of cardiac pacing and tachyarrhythmia devices, Cleveland Clinic, agreed. He said the focus should not be restricted to the iPhone 12 series but other wearable devices as alluded to in the study.

“Pacemakers and implantable defibrillators are designed to respond to magnets for important reasons, but magnets have many common uses,” he said. These can change the function of the implantable cardiac devise, but “it is temporary and only when placed in close proximity.”

The solution is simple. “Patients should be careful to avoid locating these objects near these devices,” Dr. Wilkoff said.

However, the first step is awareness. According to the study authors, devices with magnets powerful enough to impair function of implantable devices, such as the iPhone 12 “can potentially inhibit lifesaving therapy.”

Patients should be counseled and provided with practical steps, according to the authors. This includes keeping these devices out of pockets near implantable devices. They called for more noise from makers of smartphones and other devices with strong enough magnets to alter pacemaker and ICD function, and they advised physicians to draw awareness to this issue.

Dr. Greenberg reported no potential conflicts of interest.