Myelodysplastic Syndrome

Key clinical point: The addition of lenalidomide (LEN) to epoetin (EPO) alfa offers a superior probability of clinically meaningful and highly durable erythroid response vs. LEN alone in patients with lower-risk, non-del (5q) myelodysplastic syndromes (MDS) who have anemia that is refractory to recombinant erythropoietin.

Major finding: After 4 cycles of treatment, major erythroid response was significantly higher with the combination of LEN and erythropoietin vs. LEN alone (28.3% vs. 11.5%; P = .004). Responses to the combined treatment were highly durable with a median major erythroid response duration of 23.8 months in the combined therapy cohort vs. 13 months in the LEN cohort.

Study details: In this phase 3 US intergroup trial, 195 patients with MDS and anemia were randomly assigned to receive LEN and EPO alfa (n = 99) or LEN alone (n = 96) following stratification by serum erythropoietin concentration and prior erythropoietin treatment.

Disclosures: The study was supported by the ECOG-ACRIN Cancer Research Group Study, the National Cancer Institute (NCI) of the National Institutes of Health, and NCI. The authors reported ties with various pharmaceutical companies.

Source: List AF et al. J Clin Oncol. 2021 Jan 13. doi: 10.1200/JCO.20.01691.

Key clinical point: The addition of lenalidomide (LEN) to epoetin (EPO) alfa offers a superior probability of clinically meaningful and highly durable erythroid response vs. LEN alone in patients with lower-risk, non-del (5q) myelodysplastic syndromes (MDS) who have anemia that is refractory to recombinant erythropoietin.

Major finding: After 4 cycles of treatment, major erythroid response was significantly higher with the combination of LEN and erythropoietin vs. LEN alone (28.3% vs. 11.5%; P = .004). Responses to the combined treatment were highly durable with a median major erythroid response duration of 23.8 months in the combined therapy cohort vs. 13 months in the LEN cohort.

Study details: In this phase 3 US intergroup trial, 195 patients with MDS and anemia were randomly assigned to receive LEN and EPO alfa (n = 99) or LEN alone (n = 96) following stratification by serum erythropoietin concentration and prior erythropoietin treatment.

Disclosures: The study was supported by the ECOG-ACRIN Cancer Research Group Study, the National Cancer Institute (NCI) of the National Institutes of Health, and NCI. The authors reported ties with various pharmaceutical companies.

Source: List AF et al. J Clin Oncol. 2021 Jan 13. doi: 10.1200/JCO.20.01691.

Key clinical point: The addition of lenalidomide (LEN) to epoetin (EPO) alfa offers a superior probability of clinically meaningful and highly durable erythroid response vs. LEN alone in patients with lower-risk, non-del (5q) myelodysplastic syndromes (MDS) who have anemia that is refractory to recombinant erythropoietin.

Major finding: After 4 cycles of treatment, major erythroid response was significantly higher with the combination of LEN and erythropoietin vs. LEN alone (28.3% vs. 11.5%; P = .004). Responses to the combined treatment were highly durable with a median major erythroid response duration of 23.8 months in the combined therapy cohort vs. 13 months in the LEN cohort.

Study details: In this phase 3 US intergroup trial, 195 patients with MDS and anemia were randomly assigned to receive LEN and EPO alfa (n = 99) or LEN alone (n = 96) following stratification by serum erythropoietin concentration and prior erythropoietin treatment.

Disclosures: The study was supported by the ECOG-ACRIN Cancer Research Group Study, the National Cancer Institute (NCI) of the National Institutes of Health, and NCI. The authors reported ties with various pharmaceutical companies.

Source: List AF et al. J Clin Oncol. 2021 Jan 13. doi: 10.1200/JCO.20.01691.

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.

Key clinical point: Researchers used flow cytometry and genomic assessment to identify a shared DNMT3A mutation in a rare case of angioimmunoblastic T-cell lymphoma and myelodysplastic syndrome.

Major finding: DNMT3A N612Rfs*36 was identified as the common mutation for AITL and myeloid neoplasm using both cytogenetic analysis (karyotype), which showed deletion of the long arm of chromosome 20 in 14 of 20 metaphases and also fluorescent in situ hybridization (FISH), which showed the same deletion in 36.3% of cells. 

Study details: The data come from a case report of a 75-year-old man with a history of lung adenocarcinoma who was diagnosed with angioimmunoblastic T-cell lymphoma (AITL) and concomitant myelodysplastic syndrome.

Disclosures: The study received no outside funding. Lead author Dr. Naganuma had no financial conflicts to disclose.

Source: Naganuma K et al. J Hematol. 2020 Nov 6. doi: 10.14740/jh760.

Key clinical point: Researchers used flow cytometry and genomic assessment to identify a shared DNMT3A mutation in a rare case of angioimmunoblastic T-cell lymphoma and myelodysplastic syndrome.

Major finding: DNMT3A N612Rfs*36 was identified as the common mutation for AITL and myeloid neoplasm using both cytogenetic analysis (karyotype), which showed deletion of the long arm of chromosome 20 in 14 of 20 metaphases and also fluorescent in situ hybridization (FISH), which showed the same deletion in 36.3% of cells. 

Study details: The data come from a case report of a 75-year-old man with a history of lung adenocarcinoma who was diagnosed with angioimmunoblastic T-cell lymphoma (AITL) and concomitant myelodysplastic syndrome.

Disclosures: The study received no outside funding. Lead author Dr. Naganuma had no financial conflicts to disclose.

Source: Naganuma K et al. J Hematol. 2020 Nov 6. doi: 10.14740/jh760.

Key clinical point: Researchers used flow cytometry and genomic assessment to identify a shared DNMT3A mutation in a rare case of angioimmunoblastic T-cell lymphoma and myelodysplastic syndrome.

Major finding: DNMT3A N612Rfs*36 was identified as the common mutation for AITL and myeloid neoplasm using both cytogenetic analysis (karyotype), which showed deletion of the long arm of chromosome 20 in 14 of 20 metaphases and also fluorescent in situ hybridization (FISH), which showed the same deletion in 36.3% of cells. 

Study details: The data come from a case report of a 75-year-old man with a history of lung adenocarcinoma who was diagnosed with angioimmunoblastic T-cell lymphoma (AITL) and concomitant myelodysplastic syndrome.

Disclosures: The study received no outside funding. Lead author Dr. Naganuma had no financial conflicts to disclose.

Source: Naganuma K et al. J Hematol. 2020 Nov 6. doi: 10.14740/jh760.

Key clinical point: Outcomes remain poor for patients with acute lymphocytic leukemia, acute myeloid leukemia, and myelodysplastic syndrome who suffer relapse after allogeneic hematopoietic cell transplantation; factors associated with mortality included acute graft vs. host disease grade II-IV.

Major finding: The cumulative incidence of morphologic relapse in patients with acute lymphocytic leukemia, acute myeloid leukemia, and myelodysplastic syndrome after allogeneic hematopoietic cell transplantation was 19%, 24%, and 26%, respectively at 12 months; the estimated median survival after relapse across all diseases was 2.9 months.

Study details: The data come from 420 adults with acute lymphocytic leukemia, acute myeloid leukemia, and myelodysplastic syndrome.

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

Source: Hong S et al. Hematol Oncol Stem Cell Ther. 2020 Dec 5. doi: 10.1016/j.hemonc.2020.11.006.

Key clinical point: Outcomes remain poor for patients with acute lymphocytic leukemia, acute myeloid leukemia, and myelodysplastic syndrome who suffer relapse after allogeneic hematopoietic cell transplantation; factors associated with mortality included acute graft vs. host disease grade II-IV.

Major finding: The cumulative incidence of morphologic relapse in patients with acute lymphocytic leukemia, acute myeloid leukemia, and myelodysplastic syndrome after allogeneic hematopoietic cell transplantation was 19%, 24%, and 26%, respectively at 12 months; the estimated median survival after relapse across all diseases was 2.9 months.

Study details: The data come from 420 adults with acute lymphocytic leukemia, acute myeloid leukemia, and myelodysplastic syndrome.

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

Source: Hong S et al. Hematol Oncol Stem Cell Ther. 2020 Dec 5. doi: 10.1016/j.hemonc.2020.11.006.

Key clinical point: Outcomes remain poor for patients with acute lymphocytic leukemia, acute myeloid leukemia, and myelodysplastic syndrome who suffer relapse after allogeneic hematopoietic cell transplantation; factors associated with mortality included acute graft vs. host disease grade II-IV.

Major finding: The cumulative incidence of morphologic relapse in patients with acute lymphocytic leukemia, acute myeloid leukemia, and myelodysplastic syndrome after allogeneic hematopoietic cell transplantation was 19%, 24%, and 26%, respectively at 12 months; the estimated median survival after relapse across all diseases was 2.9 months.

Study details: The data come from 420 adults with acute lymphocytic leukemia, acute myeloid leukemia, and myelodysplastic syndrome.

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

Source: Hong S et al. Hematol Oncol Stem Cell Ther. 2020 Dec 5. doi: 10.1016/j.hemonc.2020.11.006.