Myelodysplastic Syndrome

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.

Key clinical point: Use of the Eastern Cooperative Oncology Group Performance Status (ECOG PS) added to the International Prognostic Scoring System, revised (IPSS-R) could identify low, intermediate, and high-risk groups of patients with patients with higher-risk myelodysplastic syndromes and oligoblastic acute myeloid leukemia.

Major finding: Serum ferritin levels < 520 ng/mL, ECOG PS scores of 0 or 1, and IPSS-R independently predicted stronger response to 5-AZA in patients with myelodysplastic syndromes and oligoblastic acute myeloid leukemia. 

Study details: The data come from a retrospective study of 687 consecutive patients with myelodysplastic syndrome and oligoblastic acute myeloid leukemia who were treated with 5-azacytidine (5-AZA).

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

Source: Papageorgiou SG et al. Ther Adv Hematol. 2020 Dec 8. doi: 10.1177/2040620720966121.

Key clinical point: Use of the Eastern Cooperative Oncology Group Performance Status (ECOG PS) added to the International Prognostic Scoring System, revised (IPSS-R) could identify low, intermediate, and high-risk groups of patients with patients with higher-risk myelodysplastic syndromes and oligoblastic acute myeloid leukemia.

Major finding: Serum ferritin levels < 520 ng/mL, ECOG PS scores of 0 or 1, and IPSS-R independently predicted stronger response to 5-AZA in patients with myelodysplastic syndromes and oligoblastic acute myeloid leukemia. 

Study details: The data come from a retrospective study of 687 consecutive patients with myelodysplastic syndrome and oligoblastic acute myeloid leukemia who were treated with 5-azacytidine (5-AZA).

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

Source: Papageorgiou SG et al. Ther Adv Hematol. 2020 Dec 8. doi: 10.1177/2040620720966121.

Key clinical point: Use of the Eastern Cooperative Oncology Group Performance Status (ECOG PS) added to the International Prognostic Scoring System, revised (IPSS-R) could identify low, intermediate, and high-risk groups of patients with patients with higher-risk myelodysplastic syndromes and oligoblastic acute myeloid leukemia.

Major finding: Serum ferritin levels < 520 ng/mL, ECOG PS scores of 0 or 1, and IPSS-R independently predicted stronger response to 5-AZA in patients with myelodysplastic syndromes and oligoblastic acute myeloid leukemia. 

Study details: The data come from a retrospective study of 687 consecutive patients with myelodysplastic syndrome and oligoblastic acute myeloid leukemia who were treated with 5-azacytidine (5-AZA).

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

Source: Papageorgiou SG et al. Ther Adv Hematol. 2020 Dec 8. doi: 10.1177/2040620720966121.

Key clinical point: Myelodysplastic syndrome patients who responded to treatment with azacytidine showed significantly reduced peripheral blood levels of Wilms’ tumour 1 mRNA (WT-1) compared to nonresponders.

Major finding: A total of 20 patients (63%) showed a response to azacytidine; 7 patients (22%) achieved complete response and 19 patients (59%) achieved hematologic improvement. Responders had an average peripheral blood WT-A mRNA of 2,050 copies per micrograms of RNA vs. 7,550 copies per micrograms of RNA for nonresponders (P = 0.03).

Study details: The data come from 32 adult patients aged 31 to 85 years with myelodysplastic syndrome who were treated with azacytidine for an average of five cycles.

Disclosures: The study was supported in part by the Practical Research for Innovative Cancer Control Program from the Japan Agency for Medical Research and Development, AMED. Lead author Dr. Maeda disclosed relationships with Nippon Shinyaku and Janssen; several coauthors also disclosed relationships with multiple companies.

Source: Maeda T et al. Leukemia Res Rep. 2020 Dec 8. doi: 10.1016/j.lrr.2020.100231.

Key clinical point: Myelodysplastic syndrome patients who responded to treatment with azacytidine showed significantly reduced peripheral blood levels of Wilms’ tumour 1 mRNA (WT-1) compared to nonresponders.

Major finding: A total of 20 patients (63%) showed a response to azacytidine; 7 patients (22%) achieved complete response and 19 patients (59%) achieved hematologic improvement. Responders had an average peripheral blood WT-A mRNA of 2,050 copies per micrograms of RNA vs. 7,550 copies per micrograms of RNA for nonresponders (P = 0.03).

Study details: The data come from 32 adult patients aged 31 to 85 years with myelodysplastic syndrome who were treated with azacytidine for an average of five cycles.

Disclosures: The study was supported in part by the Practical Research for Innovative Cancer Control Program from the Japan Agency for Medical Research and Development, AMED. Lead author Dr. Maeda disclosed relationships with Nippon Shinyaku and Janssen; several coauthors also disclosed relationships with multiple companies.

Source: Maeda T et al. Leukemia Res Rep. 2020 Dec 8. doi: 10.1016/j.lrr.2020.100231.

Key clinical point: Myelodysplastic syndrome patients who responded to treatment with azacytidine showed significantly reduced peripheral blood levels of Wilms’ tumour 1 mRNA (WT-1) compared to nonresponders.

Major finding: A total of 20 patients (63%) showed a response to azacytidine; 7 patients (22%) achieved complete response and 19 patients (59%) achieved hematologic improvement. Responders had an average peripheral blood WT-A mRNA of 2,050 copies per micrograms of RNA vs. 7,550 copies per micrograms of RNA for nonresponders (P = 0.03).

Study details: The data come from 32 adult patients aged 31 to 85 years with myelodysplastic syndrome who were treated with azacytidine for an average of five cycles.

Disclosures: The study was supported in part by the Practical Research for Innovative Cancer Control Program from the Japan Agency for Medical Research and Development, AMED. Lead author Dr. Maeda disclosed relationships with Nippon Shinyaku and Janssen; several coauthors also disclosed relationships with multiple companies.

Source: Maeda T et al. Leukemia Res Rep. 2020 Dec 8. doi: 10.1016/j.lrr.2020.100231.

Key clinical point: A simplified system based on four clinical parameters of the flow cytometric score (MFCM-Score) was positively correlated with the Revised International Prognostic Scoring System (IPSS-R) for myelodysplastic syndrome.

Major finding: No significant difference appeared between the MFCM-score and FCM-score in diagnosing myelodysplastic syndrome (P > 0.05).

Study details: The data come from 118 adults with suspected myelodysplastic syndrome. Patients were compared using the FCM and MFCM. Four parameters were used in the standard FCM scoring: myeloblast-related cluster size (myeloblast-related cells/all nucleated cell), B-progenitor-related cluster size (B-progenitor-related cells/all CD34⁺ cells), CD45 mean fluorescence intensity (MFI) ratio (lymphocytes/myeloid blast cells), and SSC peak channel ratio (granulocyte/lymphocyte). The MFCM simplified the scoring further by using CD19 and CD33 to separate B lymphocyte progenitor cells and myeloblasts within the CD34⁺CD45^dimm population.

Disclosures: The study was funded by the National Natural Science Foundation of China and the Natural Science Research Project of Anhui Medical University. The researchers had no financial conflicts to disclose.

Source: Guo J et al. Am J Transl Res. 2020 Nov 15. 12(11):7449–7458.

Key clinical point: A simplified system based on four clinical parameters of the flow cytometric score (MFCM-Score) was positively correlated with the Revised International Prognostic Scoring System (IPSS-R) for myelodysplastic syndrome.

Major finding: No significant difference appeared between the MFCM-score and FCM-score in diagnosing myelodysplastic syndrome (P > 0.05).

Study details: The data come from 118 adults with suspected myelodysplastic syndrome. Patients were compared using the FCM and MFCM. Four parameters were used in the standard FCM scoring: myeloblast-related cluster size (myeloblast-related cells/all nucleated cell), B-progenitor-related cluster size (B-progenitor-related cells/all CD34⁺ cells), CD45 mean fluorescence intensity (MFI) ratio (lymphocytes/myeloid blast cells), and SSC peak channel ratio (granulocyte/lymphocyte). The MFCM simplified the scoring further by using CD19 and CD33 to separate B lymphocyte progenitor cells and myeloblasts within the CD34⁺CD45^dimm population.

Disclosures: The study was funded by the National Natural Science Foundation of China and the Natural Science Research Project of Anhui Medical University. The researchers had no financial conflicts to disclose.

Source: Guo J et al. Am J Transl Res. 2020 Nov 15. 12(11):7449–7458.

Key clinical point: A simplified system based on four clinical parameters of the flow cytometric score (MFCM-Score) was positively correlated with the Revised International Prognostic Scoring System (IPSS-R) for myelodysplastic syndrome.

Major finding: No significant difference appeared between the MFCM-score and FCM-score in diagnosing myelodysplastic syndrome (P > 0.05).

Study details: The data come from 118 adults with suspected myelodysplastic syndrome. Patients were compared using the FCM and MFCM. Four parameters were used in the standard FCM scoring: myeloblast-related cluster size (myeloblast-related cells/all nucleated cell), B-progenitor-related cluster size (B-progenitor-related cells/all CD34⁺ cells), CD45 mean fluorescence intensity (MFI) ratio (lymphocytes/myeloid blast cells), and SSC peak channel ratio (granulocyte/lymphocyte). The MFCM simplified the scoring further by using CD19 and CD33 to separate B lymphocyte progenitor cells and myeloblasts within the CD34⁺CD45^dimm population.

Disclosures: The study was funded by the National Natural Science Foundation of China and the Natural Science Research Project of Anhui Medical University. The researchers had no financial conflicts to disclose.

Source: Guo J et al. Am J Transl Res. 2020 Nov 15. 12(11):7449–7458.

Key clinical point: Overall survival improved by more than 20% in older adults with myelodysplastic syndrome who received allogeneic stem cell transplantation.

Major finding: Overall survival at 3 years was 47.9% for patients who received allogeneic hematopoietic cell transplantation compared to those who did not.

Study details: The data come from myelodysplastic syndrome patients with a median age of 66 years who were part of the prospective Blood and Marrow Transplant Clinical Trials Network (BMT CTN) Study 1102 (NCT02016781) presented at the American Society of Hematology (ASH) 2020 virtual meeting.

Disclosures: Lead author Dr. Cutler disclosed serving as a consultant for Mesoblast, Generon, Medsenic, Jazz, Kadmon, and Incyte.

Source: Cutler C et al. ASH 2020.

Key clinical point: Overall survival improved by more than 20% in older adults with myelodysplastic syndrome who received allogeneic stem cell transplantation.

Major finding: Overall survival at 3 years was 47.9% for patients who received allogeneic hematopoietic cell transplantation compared to those who did not.

Study details: The data come from myelodysplastic syndrome patients with a median age of 66 years who were part of the prospective Blood and Marrow Transplant Clinical Trials Network (BMT CTN) Study 1102 (NCT02016781) presented at the American Society of Hematology (ASH) 2020 virtual meeting.

Disclosures: Lead author Dr. Cutler disclosed serving as a consultant for Mesoblast, Generon, Medsenic, Jazz, Kadmon, and Incyte.

Source: Cutler C et al. ASH 2020.

Key clinical point: Overall survival improved by more than 20% in older adults with myelodysplastic syndrome who received allogeneic stem cell transplantation.

Major finding: Overall survival at 3 years was 47.9% for patients who received allogeneic hematopoietic cell transplantation compared to those who did not.

Study details: The data come from myelodysplastic syndrome patients with a median age of 66 years who were part of the prospective Blood and Marrow Transplant Clinical Trials Network (BMT CTN) Study 1102 (NCT02016781) presented at the American Society of Hematology (ASH) 2020 virtual meeting.

Disclosures: Lead author Dr. Cutler disclosed serving as a consultant for Mesoblast, Generon, Medsenic, Jazz, Kadmon, and Incyte.

Source: Cutler C et al. ASH 2020.

Key clinical point: Incidence of graft vs. host disease was significantly lower in patients undergoing matched sibling donor stem cell transplants who received low-dose rabbit antitymoctye globulin (rATG).

Major finding: The 2-year cumulative incidences of chronic GVHD (cGVHD) were 35.4% and 60.4%, respectively, for patients in the rATG and non-rATG groups (P=0.039).

Study details: The data come from a retrospective study of 79 patients aged 16 years and older with hematologic malignancies who were treated with matched sibling donor hematopoietic stem cell transplantation (MSD-HSCT); all received standard prophylaxis and 38 received 5 mg/kg of rATG in addition.

Disclosures: The study was supported in part by the Scientific Research Seed Fund of Peking University First Hospital. The researchers had no financial conflicts to disclose.

Source: Song ZY et al. Cancer Manag Res. 2020 Nov 30. doi: 10.2147/CMAR.S283855.

Key clinical point: Incidence of graft vs. host disease was significantly lower in patients undergoing matched sibling donor stem cell transplants who received low-dose rabbit antitymoctye globulin (rATG).

Major finding: The 2-year cumulative incidences of chronic GVHD (cGVHD) were 35.4% and 60.4%, respectively, for patients in the rATG and non-rATG groups (P=0.039).

Study details: The data come from a retrospective study of 79 patients aged 16 years and older with hematologic malignancies who were treated with matched sibling donor hematopoietic stem cell transplantation (MSD-HSCT); all received standard prophylaxis and 38 received 5 mg/kg of rATG in addition.

Disclosures: The study was supported in part by the Scientific Research Seed Fund of Peking University First Hospital. The researchers had no financial conflicts to disclose.

Source: Song ZY et al. Cancer Manag Res. 2020 Nov 30. doi: 10.2147/CMAR.S283855.

Key clinical point: Incidence of graft vs. host disease was significantly lower in patients undergoing matched sibling donor stem cell transplants who received low-dose rabbit antitymoctye globulin (rATG).

Major finding: The 2-year cumulative incidences of chronic GVHD (cGVHD) were 35.4% and 60.4%, respectively, for patients in the rATG and non-rATG groups (P=0.039).

Study details: The data come from a retrospective study of 79 patients aged 16 years and older with hematologic malignancies who were treated with matched sibling donor hematopoietic stem cell transplantation (MSD-HSCT); all received standard prophylaxis and 38 received 5 mg/kg of rATG in addition.

Disclosures: The study was supported in part by the Scientific Research Seed Fund of Peking University First Hospital. The researchers had no financial conflicts to disclose.

Source: Song ZY et al. Cancer Manag Res. 2020 Nov 30. doi: 10.2147/CMAR.S283855.

Key clinical point: The compound APR‐246 (PRIMA‐1Met/Eprenetapopt) caused synergistic tumor death in myelodysplastic syndrome with combined with inhibitors of efflux pump MRP1/ABCC1.

Major finding: A combination of combination of APR‐246 with the MRP1 inhibitor MK‐571 significantly reduced IC₅₀ values in 21 cell lines (P < 0.0001).

Study details: The data come from a combination of in vitro, ex vivo, and in vivo models, using combined treatment of APR‐246 and inhibitors of efflux pump MRP1/ABCC1. 

Disclosures: The study was funded by multiple organizations including Vetenskapsrådet, Cancerfonden (Swedish Cancer Society), Barncancerfonden (Swedish Childhood Cancer Foundation), Radiumhemmets Forskningsfonder (Cancer Research Foundations of Radiumhemmet, Knut och Alice Wallenbergs Stiftelse (Knut and Alice Wallenberg Foundation), Aprea Therapeutics, Karolinska Institutet (KI), Department of Health, Australian Government/National Health and Medical Research Council (NHMRC), Department of Health and Human Services, State Government of Victoria (DHHS), Tour de Cure Foundation, UKRI/Medical Research Council (MRC), Australian Cancer Research Foundation (ACRF), Australian Government’s National Collaborative Research Infrastructure Strategy (NCRIS) program, Peter MacCallum Cancer Centre Foundation, University of Melbourne Research Collaborative Infrastructure Program (MCRIP), and Cancer Research UK.

Source: Ceder S et al. EMBO Mol Med. 2020 Dec 14. doi: 10.15252/emmm.201910852.

Key clinical point: The compound APR‐246 (PRIMA‐1Met/Eprenetapopt) caused synergistic tumor death in myelodysplastic syndrome with combined with inhibitors of efflux pump MRP1/ABCC1.

Major finding: A combination of combination of APR‐246 with the MRP1 inhibitor MK‐571 significantly reduced IC₅₀ values in 21 cell lines (P < 0.0001).

Study details: The data come from a combination of in vitro, ex vivo, and in vivo models, using combined treatment of APR‐246 and inhibitors of efflux pump MRP1/ABCC1. 

Disclosures: The study was funded by multiple organizations including Vetenskapsrådet, Cancerfonden (Swedish Cancer Society), Barncancerfonden (Swedish Childhood Cancer Foundation), Radiumhemmets Forskningsfonder (Cancer Research Foundations of Radiumhemmet, Knut och Alice Wallenbergs Stiftelse (Knut and Alice Wallenberg Foundation), Aprea Therapeutics, Karolinska Institutet (KI), Department of Health, Australian Government/National Health and Medical Research Council (NHMRC), Department of Health and Human Services, State Government of Victoria (DHHS), Tour de Cure Foundation, UKRI/Medical Research Council (MRC), Australian Cancer Research Foundation (ACRF), Australian Government’s National Collaborative Research Infrastructure Strategy (NCRIS) program, Peter MacCallum Cancer Centre Foundation, University of Melbourne Research Collaborative Infrastructure Program (MCRIP), and Cancer Research UK.

Source: Ceder S et al. EMBO Mol Med. 2020 Dec 14. doi: 10.15252/emmm.201910852.

Key clinical point: The compound APR‐246 (PRIMA‐1Met/Eprenetapopt) caused synergistic tumor death in myelodysplastic syndrome with combined with inhibitors of efflux pump MRP1/ABCC1.

Major finding: A combination of combination of APR‐246 with the MRP1 inhibitor MK‐571 significantly reduced IC₅₀ values in 21 cell lines (P < 0.0001).

Study details: The data come from a combination of in vitro, ex vivo, and in vivo models, using combined treatment of APR‐246 and inhibitors of efflux pump MRP1/ABCC1. 

Disclosures: The study was funded by multiple organizations including Vetenskapsrådet, Cancerfonden (Swedish Cancer Society), Barncancerfonden (Swedish Childhood Cancer Foundation), Radiumhemmets Forskningsfonder (Cancer Research Foundations of Radiumhemmet, Knut och Alice Wallenbergs Stiftelse (Knut and Alice Wallenberg Foundation), Aprea Therapeutics, Karolinska Institutet (KI), Department of Health, Australian Government/National Health and Medical Research Council (NHMRC), Department of Health and Human Services, State Government of Victoria (DHHS), Tour de Cure Foundation, UKRI/Medical Research Council (MRC), Australian Cancer Research Foundation (ACRF), Australian Government’s National Collaborative Research Infrastructure Strategy (NCRIS) program, Peter MacCallum Cancer Centre Foundation, University of Melbourne Research Collaborative Infrastructure Program (MCRIP), and Cancer Research UK.

Source: Ceder S et al. EMBO Mol Med. 2020 Dec 14. doi: 10.15252/emmm.201910852.

Key clinical point: Researchers developed a flow score based on three variables: developed a “flow score” with the three variables percentage of myeloid CD34⁺ cells > 2%; percentage of B-cell progenitors < 0.05%; and CD16⁺ monocytes/TNCs > 1.0%.

Major finding: Of the 95 patients in the study, 23 remained alive after the end of the study period. A high percentage of CD16⁺ monocytes/TNCs > 1.0% (in the highest quartile) was associated with significantly worse survival.

Study details: The data come from 95 adult patients with newly diagnosed myelodysplastic syndrome seen at a single center and followed for an average of 42 months.

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

Source: Vido-Marques JR et al. Sci Rep. 2020 Nov 20. doi: 10.1038/s41598-020-77158-z.

Key clinical point: Researchers developed a flow score based on three variables: developed a “flow score” with the three variables percentage of myeloid CD34⁺ cells > 2%; percentage of B-cell progenitors < 0.05%; and CD16⁺ monocytes/TNCs > 1.0%.

Major finding: Of the 95 patients in the study, 23 remained alive after the end of the study period. A high percentage of CD16⁺ monocytes/TNCs > 1.0% (in the highest quartile) was associated with significantly worse survival.

Study details: The data come from 95 adult patients with newly diagnosed myelodysplastic syndrome seen at a single center and followed for an average of 42 months.

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

Source: Vido-Marques JR et al. Sci Rep. 2020 Nov 20. doi: 10.1038/s41598-020-77158-z.

Key clinical point: Researchers developed a flow score based on three variables: developed a “flow score” with the three variables percentage of myeloid CD34⁺ cells > 2%; percentage of B-cell progenitors < 0.05%; and CD16⁺ monocytes/TNCs > 1.0%.

Major finding: Of the 95 patients in the study, 23 remained alive after the end of the study period. A high percentage of CD16⁺ monocytes/TNCs > 1.0% (in the highest quartile) was associated with significantly worse survival.

Study details: The data come from 95 adult patients with newly diagnosed myelodysplastic syndrome seen at a single center and followed for an average of 42 months.

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

Source: Vido-Marques JR et al. Sci Rep. 2020 Nov 20. doi: 10.1038/s41598-020-77158-z.