Myelodysplastic Syndrome

Key clinical point: High fibrinogen-albumin ratio index (FARI) is associated with shorter overall survival (OS) in patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) treated with azacitidine.

Major finding: One-year OS was significantly shorter in patients with high (at or above 0.079) vs. low (less than 0.079) FARI (35.6% vs. 77.5%; P less than .001).

Study details: Findings are from a retrospective study of 99 patients with de novo MDS (n=86) and AML-MRC (n=13) treated with azacitidine between May 2011 and June 2019.

Disclosures: The authors did not report any source of funding. The authors declared no potential competing interests.

Source: Akimoto M et al. Ann Hematol. 2021 Feb 1. doi: 10.1007/s00277-021-04440-z.

Key clinical point: High fibrinogen-albumin ratio index (FARI) is associated with shorter overall survival (OS) in patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) treated with azacitidine.

Major finding: One-year OS was significantly shorter in patients with high (at or above 0.079) vs. low (less than 0.079) FARI (35.6% vs. 77.5%; P less than .001).

Study details: Findings are from a retrospective study of 99 patients with de novo MDS (n=86) and AML-MRC (n=13) treated with azacitidine between May 2011 and June 2019.

Disclosures: The authors did not report any source of funding. The authors declared no potential competing interests.

Source: Akimoto M et al. Ann Hematol. 2021 Feb 1. doi: 10.1007/s00277-021-04440-z.

Key clinical point: High fibrinogen-albumin ratio index (FARI) is associated with shorter overall survival (OS) in patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) treated with azacitidine.

Major finding: One-year OS was significantly shorter in patients with high (at or above 0.079) vs. low (less than 0.079) FARI (35.6% vs. 77.5%; P less than .001).

Study details: Findings are from a retrospective study of 99 patients with de novo MDS (n=86) and AML-MRC (n=13) treated with azacitidine between May 2011 and June 2019.

Disclosures: The authors did not report any source of funding. The authors declared no potential competing interests.

Source: Akimoto M et al. Ann Hematol. 2021 Feb 1. doi: 10.1007/s00277-021-04440-z.

Key clinical point: Reduced-dose decitabine (DAC) could have a better response than reduced-dose azacitidine (AZA) in patients with myelodysplastic syndromes (MDS) with different prognostic risks.

Major finding: Overall response rate (ORR) was higher in the DAC (62.5%) than AZA (42.1%) group (P = .007). Incidences of neutropenia (P = .016) and infections (P = .032) were higher in the DAC vs. AZA group.

Study details: Findings are from a retrospective study of 158 patients with MDS with varied prognostic risks who were administered reduced-dose of AZA (n=38) or DAC (n=120). Included patients received these hypomethylating agents for the first time between May 2006 and February 2020 and could not tolerate the standard doses.

Disclosures: The study was funded by the National Science and Technology Major Project of China. The authors declared no competing interests.

Source: Hu N et al. Med Sci Monit. 2021 Jan 30. doi: 10.12659/MSM.928454.

Key clinical point: Reduced-dose decitabine (DAC) could have a better response than reduced-dose azacitidine (AZA) in patients with myelodysplastic syndromes (MDS) with different prognostic risks.

Major finding: Overall response rate (ORR) was higher in the DAC (62.5%) than AZA (42.1%) group (P = .007). Incidences of neutropenia (P = .016) and infections (P = .032) were higher in the DAC vs. AZA group.

Study details: Findings are from a retrospective study of 158 patients with MDS with varied prognostic risks who were administered reduced-dose of AZA (n=38) or DAC (n=120). Included patients received these hypomethylating agents for the first time between May 2006 and February 2020 and could not tolerate the standard doses.

Disclosures: The study was funded by the National Science and Technology Major Project of China. The authors declared no competing interests.

Source: Hu N et al. Med Sci Monit. 2021 Jan 30. doi: 10.12659/MSM.928454.

Key clinical point: Reduced-dose decitabine (DAC) could have a better response than reduced-dose azacitidine (AZA) in patients with myelodysplastic syndromes (MDS) with different prognostic risks.

Major finding: Overall response rate (ORR) was higher in the DAC (62.5%) than AZA (42.1%) group (P = .007). Incidences of neutropenia (P = .016) and infections (P = .032) were higher in the DAC vs. AZA group.

Study details: Findings are from a retrospective study of 158 patients with MDS with varied prognostic risks who were administered reduced-dose of AZA (n=38) or DAC (n=120). Included patients received these hypomethylating agents for the first time between May 2006 and February 2020 and could not tolerate the standard doses.

Disclosures: The study was funded by the National Science and Technology Major Project of China. The authors declared no competing interests.

Source: Hu N et al. Med Sci Monit. 2021 Jan 30. doi: 10.12659/MSM.928454.

Key clinical point: Daratumumab provided some clinical activity in patients with low- to intermediate-risk myelodysplastic syndromes (MDS), who relapsed or were refractory to erythropoiesis-stimulating agents (ESA) treatment. No new safety signals were identified.

Major finding: Eight-week transfusion independence (TI) was achieved by 6.1% (95% confidence interval, 0.7%-20.2%) of patients. Time to 8-week TI was 4–5 weeks after the first daratumumab infusion. Daratumumab-related adverse events were reported by 54.5% of patients, of whom 3 patients experienced 4 serious adverse events. Infusion-related reaction was observed, but none led to treatment discontinuation.

Study details: Findings are from a phase 2, randomized, open-label study involving 34 patients with low- or intermediate-1-risk MDS, who were transfusion dependent and who relapsed or were refractory to ESA treatment. Patients received either daratumumab (n=33) or talacotuzumab (n=1); however, recruitment to talacotuzumab arm was closed after the occurrence of a serious adverse event in the first patient.

Disclosures: This study was supported by Janssen Research & Development. The lead author reported receiving research support from Johnson & Johnson. Some of the coinvestigators reported owning stocks, being an employee, serving on an advisory board, receiving support, and consulting for various pharmaceutical companies including Janssen Research & Development. Six of the coinvestigators declared no potential competing interests.

Source: Garcia‐Manero G et al. Am J Hematol. 2021 Jan 15. doi: 10.1002/ajh.26095.

Key clinical point: Daratumumab provided some clinical activity in patients with low- to intermediate-risk myelodysplastic syndromes (MDS), who relapsed or were refractory to erythropoiesis-stimulating agents (ESA) treatment. No new safety signals were identified.

Major finding: Eight-week transfusion independence (TI) was achieved by 6.1% (95% confidence interval, 0.7%-20.2%) of patients. Time to 8-week TI was 4–5 weeks after the first daratumumab infusion. Daratumumab-related adverse events were reported by 54.5% of patients, of whom 3 patients experienced 4 serious adverse events. Infusion-related reaction was observed, but none led to treatment discontinuation.

Study details: Findings are from a phase 2, randomized, open-label study involving 34 patients with low- or intermediate-1-risk MDS, who were transfusion dependent and who relapsed or were refractory to ESA treatment. Patients received either daratumumab (n=33) or talacotuzumab (n=1); however, recruitment to talacotuzumab arm was closed after the occurrence of a serious adverse event in the first patient.

Disclosures: This study was supported by Janssen Research & Development. The lead author reported receiving research support from Johnson & Johnson. Some of the coinvestigators reported owning stocks, being an employee, serving on an advisory board, receiving support, and consulting for various pharmaceutical companies including Janssen Research & Development. Six of the coinvestigators declared no potential competing interests.

Source: Garcia‐Manero G et al. Am J Hematol. 2021 Jan 15. doi: 10.1002/ajh.26095.

Key clinical point: Daratumumab provided some clinical activity in patients with low- to intermediate-risk myelodysplastic syndromes (MDS), who relapsed or were refractory to erythropoiesis-stimulating agents (ESA) treatment. No new safety signals were identified.

Major finding: Eight-week transfusion independence (TI) was achieved by 6.1% (95% confidence interval, 0.7%-20.2%) of patients. Time to 8-week TI was 4–5 weeks after the first daratumumab infusion. Daratumumab-related adverse events were reported by 54.5% of patients, of whom 3 patients experienced 4 serious adverse events. Infusion-related reaction was observed, but none led to treatment discontinuation.

Study details: Findings are from a phase 2, randomized, open-label study involving 34 patients with low- or intermediate-1-risk MDS, who were transfusion dependent and who relapsed or were refractory to ESA treatment. Patients received either daratumumab (n=33) or talacotuzumab (n=1); however, recruitment to talacotuzumab arm was closed after the occurrence of a serious adverse event in the first patient.

Disclosures: This study was supported by Janssen Research & Development. The lead author reported receiving research support from Johnson & Johnson. Some of the coinvestigators reported owning stocks, being an employee, serving on an advisory board, receiving support, and consulting for various pharmaceutical companies including Janssen Research & Development. Six of the coinvestigators declared no potential competing interests.

Source: Garcia‐Manero G et al. Am J Hematol. 2021 Jan 15. doi: 10.1002/ajh.26095.

Key clinical point: A myeloablative, fractionated busulfan (f-Bu) regimen reduces relapse and boosts survival without increasing nonrelapse mortality (NRM) in older patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS).

Major finding: At 2 years, the f-Bu group had a significantly better progression-free survival than the nonfractionated, lower dose busalfan (Bu) group (45% vs 24%; hazard ratio [HR], 0.6; P = .004), attributed to a significant reduction in progression (34% vs 59%; HR, 0.5; P = .003) without an increase in NRM (21% vs 15%; HR, 1.4; P = .3). Overall survival also improved in the f-Bu group vs the Bu group (51% vs 31%, HR, 0.6; P = .01).

Study details: In an open-label, phase 2 trial, patients with AML or MDS were randomly assigned to either myeloablative f-Bu over 2 weeks (n = 84; median age, 65 years) or a standard Bu regimen over 4 days (n = 78; median age, 66 years).

Disclosures: This study was supported in part by a grant from the National Cancer Institute. Q Bashir, C Hosing, K Rezvani and UR Popat reported relationships with various pharmaceutical companies and/or research organizations. The remaining authors declared no conflicts of interest.

Source: Oran B et al. Cancer. 2021 Jan 20. doi: 10.1002/cncr.33383

Key clinical point: A myeloablative, fractionated busulfan (f-Bu) regimen reduces relapse and boosts survival without increasing nonrelapse mortality (NRM) in older patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS).

Major finding: At 2 years, the f-Bu group had a significantly better progression-free survival than the nonfractionated, lower dose busalfan (Bu) group (45% vs 24%; hazard ratio [HR], 0.6; P = .004), attributed to a significant reduction in progression (34% vs 59%; HR, 0.5; P = .003) without an increase in NRM (21% vs 15%; HR, 1.4; P = .3). Overall survival also improved in the f-Bu group vs the Bu group (51% vs 31%, HR, 0.6; P = .01).

Study details: In an open-label, phase 2 trial, patients with AML or MDS were randomly assigned to either myeloablative f-Bu over 2 weeks (n = 84; median age, 65 years) or a standard Bu regimen over 4 days (n = 78; median age, 66 years).

Disclosures: This study was supported in part by a grant from the National Cancer Institute. Q Bashir, C Hosing, K Rezvani and UR Popat reported relationships with various pharmaceutical companies and/or research organizations. The remaining authors declared no conflicts of interest.

Source: Oran B et al. Cancer. 2021 Jan 20. doi: 10.1002/cncr.33383

Key clinical point: A myeloablative, fractionated busulfan (f-Bu) regimen reduces relapse and boosts survival without increasing nonrelapse mortality (NRM) in older patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS).

Major finding: At 2 years, the f-Bu group had a significantly better progression-free survival than the nonfractionated, lower dose busalfan (Bu) group (45% vs 24%; hazard ratio [HR], 0.6; P = .004), attributed to a significant reduction in progression (34% vs 59%; HR, 0.5; P = .003) without an increase in NRM (21% vs 15%; HR, 1.4; P = .3). Overall survival also improved in the f-Bu group vs the Bu group (51% vs 31%, HR, 0.6; P = .01).

Study details: In an open-label, phase 2 trial, patients with AML or MDS were randomly assigned to either myeloablative f-Bu over 2 weeks (n = 84; median age, 65 years) or a standard Bu regimen over 4 days (n = 78; median age, 66 years).

Disclosures: This study was supported in part by a grant from the National Cancer Institute. Q Bashir, C Hosing, K Rezvani and UR Popat reported relationships with various pharmaceutical companies and/or research organizations. The remaining authors declared no conflicts of interest.

Source: Oran B et al. Cancer. 2021 Jan 20. doi: 10.1002/cncr.33383

Key clinical point: Baseline and serial molecular profiling by next-generation sequencing (NGS) can predict outcomes with hypomethylating agents (HMAs) in myelodysplastic syndromes (MDS). Serial molecular profiling during therapy of patients with mutant TP53 can identify patients who may benefit from allogeneic transplantation.

Major finding: Mutations in TET2 and ASXL1 genes emerged as the most informative variables associated with response to HMA therapy (overall response rate, 62.1%; complete remission rate, 34.5%). The number of mutations detected by NGS (hazard ratio [HR], 1.22; P = .02) and mutations in TP53 (HR, 2.33; P = .001) and EZH2 (HR, 2.41; P = .04) were independent covariates associated with inferior overall survival (OS). Serial molecular profiling demonstrated that clearance of TP53 mutations during HMA therapy was associated with superior OS (HR, 0.28; P = .001) and improved outcome in patients proceeding to allogeneic transplantation.

Study details: This study evaluated response and OS in 247 patients molecularly profiled by NGS before first-line HMA therapy; a subset of 108 patients were sequenced serially during treatment.

Disclosures: This study was supported in part by the S Foundation Young Investigator Grant, the Early Career Award of the Dresner Foundation, and the Edward P. Evans Foundation Award. DA Sallman, E Padron, and AF List received research funding from Celgene. The remaining authors declared no conflicts of interest.

Source: Hunter AM et al. Blood Adv. 2021 Feb 23. doi: 10.1182/bloodadvances.2020003508.

Key clinical point: Baseline and serial molecular profiling by next-generation sequencing (NGS) can predict outcomes with hypomethylating agents (HMAs) in myelodysplastic syndromes (MDS). Serial molecular profiling during therapy of patients with mutant TP53 can identify patients who may benefit from allogeneic transplantation.

Major finding: Mutations in TET2 and ASXL1 genes emerged as the most informative variables associated with response to HMA therapy (overall response rate, 62.1%; complete remission rate, 34.5%). The number of mutations detected by NGS (hazard ratio [HR], 1.22; P = .02) and mutations in TP53 (HR, 2.33; P = .001) and EZH2 (HR, 2.41; P = .04) were independent covariates associated with inferior overall survival (OS). Serial molecular profiling demonstrated that clearance of TP53 mutations during HMA therapy was associated with superior OS (HR, 0.28; P = .001) and improved outcome in patients proceeding to allogeneic transplantation.

Study details: This study evaluated response and OS in 247 patients molecularly profiled by NGS before first-line HMA therapy; a subset of 108 patients were sequenced serially during treatment.

Disclosures: This study was supported in part by the S Foundation Young Investigator Grant, the Early Career Award of the Dresner Foundation, and the Edward P. Evans Foundation Award. DA Sallman, E Padron, and AF List received research funding from Celgene. The remaining authors declared no conflicts of interest.

Source: Hunter AM et al. Blood Adv. 2021 Feb 23. doi: 10.1182/bloodadvances.2020003508.

Key clinical point: Baseline and serial molecular profiling by next-generation sequencing (NGS) can predict outcomes with hypomethylating agents (HMAs) in myelodysplastic syndromes (MDS). Serial molecular profiling during therapy of patients with mutant TP53 can identify patients who may benefit from allogeneic transplantation.

Major finding: Mutations in TET2 and ASXL1 genes emerged as the most informative variables associated with response to HMA therapy (overall response rate, 62.1%; complete remission rate, 34.5%). The number of mutations detected by NGS (hazard ratio [HR], 1.22; P = .02) and mutations in TP53 (HR, 2.33; P = .001) and EZH2 (HR, 2.41; P = .04) were independent covariates associated with inferior overall survival (OS). Serial molecular profiling demonstrated that clearance of TP53 mutations during HMA therapy was associated with superior OS (HR, 0.28; P = .001) and improved outcome in patients proceeding to allogeneic transplantation.

Study details: This study evaluated response and OS in 247 patients molecularly profiled by NGS before first-line HMA therapy; a subset of 108 patients were sequenced serially during treatment.

Disclosures: This study was supported in part by the S Foundation Young Investigator Grant, the Early Career Award of the Dresner Foundation, and the Edward P. Evans Foundation Award. DA Sallman, E Padron, and AF List received research funding from Celgene. The remaining authors declared no conflicts of interest.

Source: Hunter AM et al. Blood Adv. 2021 Feb 23. doi: 10.1182/bloodadvances.2020003508.

Key clinical point: Dysregulated erythroferrone (ERFE) expression in CD71⁺ erythroid progenitors is associated with myelodysplastic syndromes (MDS) outcome and predicts patient survival independently of International Prognostic Scoring System (IPSS) stratification.

Major finding: The expression of ERFE was significantly higher in CD71⁺ cells of MDS patients vs. healthy donors group (median normalized mean fold change, 2.42 vs. 0.78). Elevated expression of ERFE in erythroid progenitors was associated with superior survival (hazard ratio, 0.35; P = .0017) independently of IPSS stratification. For growth/differentiation factor 15, the result was similar, but not statistically significant (P = .0543).

Study details: The data come from a study of 111 patients with MDS (median age, 73 years; 66.7% males).

Disclosures: This study was supported by funds of the Deutsche Forschungsgemeinschaft. The authors declared no conflicts of interest.

Source: Riabov V et al. Br J Haematol. 2021 Jan 24. doi: 10.1111/bjh.17314.

Key clinical point: Dysregulated erythroferrone (ERFE) expression in CD71⁺ erythroid progenitors is associated with myelodysplastic syndromes (MDS) outcome and predicts patient survival independently of International Prognostic Scoring System (IPSS) stratification.

Major finding: The expression of ERFE was significantly higher in CD71⁺ cells of MDS patients vs. healthy donors group (median normalized mean fold change, 2.42 vs. 0.78). Elevated expression of ERFE in erythroid progenitors was associated with superior survival (hazard ratio, 0.35; P = .0017) independently of IPSS stratification. For growth/differentiation factor 15, the result was similar, but not statistically significant (P = .0543).

Study details: The data come from a study of 111 patients with MDS (median age, 73 years; 66.7% males).

Disclosures: This study was supported by funds of the Deutsche Forschungsgemeinschaft. The authors declared no conflicts of interest.

Source: Riabov V et al. Br J Haematol. 2021 Jan 24. doi: 10.1111/bjh.17314.

Key clinical point: Dysregulated erythroferrone (ERFE) expression in CD71⁺ erythroid progenitors is associated with myelodysplastic syndromes (MDS) outcome and predicts patient survival independently of International Prognostic Scoring System (IPSS) stratification.

Major finding: The expression of ERFE was significantly higher in CD71⁺ cells of MDS patients vs. healthy donors group (median normalized mean fold change, 2.42 vs. 0.78). Elevated expression of ERFE in erythroid progenitors was associated with superior survival (hazard ratio, 0.35; P = .0017) independently of IPSS stratification. For growth/differentiation factor 15, the result was similar, but not statistically significant (P = .0543).

Study details: The data come from a study of 111 patients with MDS (median age, 73 years; 66.7% males).

Disclosures: This study was supported by funds of the Deutsche Forschungsgemeinschaft. The authors declared no conflicts of interest.

Source: Riabov V et al. Br J Haematol. 2021 Jan 24. doi: 10.1111/bjh.17314.

Key clinical point: A novel risk scoring system termed 'mutation combined with revised international prognostic scoring system (MIPSS-R)' was more effective in predicting prognosis and guiding treatment in patients with myelodysplastic syndromes (MDS) than the revised international prognostic scoring system (IPSS-R).

Major finding: Kaplan-Meier survival curves demonstrated superiority of MIPSS-R over IPSS-R in separating patients from different groups in the training cohort (P = 1.71e-08 vs P = 1.363e-04) and in the validation cohort (P = 1.788e-04 vs P = 2.757e-03). Area under the receiver operating characteristic of MIPSS-R was 0.79 in the training cohort and 0.62 in the validation cohort.

Study details: MIPSS-R was developed by integrating IPSS-R and the mutation scores. MIPSS-R was further compared with IPSS-R in a training cohort of 63 MDS patients and a validation cohort of 141 MDS patients. 

Disclosures: The study was supported in part by The National Natural Science Foundation of China, Jiangsu Provincial Special Program of Medical Science, Jiangsu Province “333” project, The Fundamental Research Funds for the Central Universities, Milstein Medical Asian American Partnership Foundation Research Project Award in Hematology, and Key Medical of Jiangsu Province. The authors declared no conflicts of interest.

Source: Gu S et al. BMC Cancer. 2021 Feb 6. doi: 10.1186/s12885-021-07864-y.

Key clinical point: A novel risk scoring system termed 'mutation combined with revised international prognostic scoring system (MIPSS-R)' was more effective in predicting prognosis and guiding treatment in patients with myelodysplastic syndromes (MDS) than the revised international prognostic scoring system (IPSS-R).

Major finding: Kaplan-Meier survival curves demonstrated superiority of MIPSS-R over IPSS-R in separating patients from different groups in the training cohort (P = 1.71e-08 vs P = 1.363e-04) and in the validation cohort (P = 1.788e-04 vs P = 2.757e-03). Area under the receiver operating characteristic of MIPSS-R was 0.79 in the training cohort and 0.62 in the validation cohort.

Study details: MIPSS-R was developed by integrating IPSS-R and the mutation scores. MIPSS-R was further compared with IPSS-R in a training cohort of 63 MDS patients and a validation cohort of 141 MDS patients. 

Disclosures: The study was supported in part by The National Natural Science Foundation of China, Jiangsu Provincial Special Program of Medical Science, Jiangsu Province “333” project, The Fundamental Research Funds for the Central Universities, Milstein Medical Asian American Partnership Foundation Research Project Award in Hematology, and Key Medical of Jiangsu Province. The authors declared no conflicts of interest.

Source: Gu S et al. BMC Cancer. 2021 Feb 6. doi: 10.1186/s12885-021-07864-y.

Key clinical point: A novel risk scoring system termed 'mutation combined with revised international prognostic scoring system (MIPSS-R)' was more effective in predicting prognosis and guiding treatment in patients with myelodysplastic syndromes (MDS) than the revised international prognostic scoring system (IPSS-R).

Major finding: Kaplan-Meier survival curves demonstrated superiority of MIPSS-R over IPSS-R in separating patients from different groups in the training cohort (P = 1.71e-08 vs P = 1.363e-04) and in the validation cohort (P = 1.788e-04 vs P = 2.757e-03). Area under the receiver operating characteristic of MIPSS-R was 0.79 in the training cohort and 0.62 in the validation cohort.

Study details: MIPSS-R was developed by integrating IPSS-R and the mutation scores. MIPSS-R was further compared with IPSS-R in a training cohort of 63 MDS patients and a validation cohort of 141 MDS patients. 

Disclosures: The study was supported in part by The National Natural Science Foundation of China, Jiangsu Provincial Special Program of Medical Science, Jiangsu Province “333” project, The Fundamental Research Funds for the Central Universities, Milstein Medical Asian American Partnership Foundation Research Project Award in Hematology, and Key Medical of Jiangsu Province. The authors declared no conflicts of interest.

Source: Gu S et al. BMC Cancer. 2021 Feb 6. doi: 10.1186/s12885-021-07864-y.

Key clinical point: In patients with myelodysplastic syndrome (MDS) with less than 5% marrow myeloblasts and no leukemic myeloblasts in blood before allogeneic hematopoietic cell transplant (alloHCT), ultra-deep DNA sequencing for mutations in 10 gene regions previously shown to be high risk in acute myeloid leukemia could help identify which patients are likely to relapse after alloHCT.

Major finding: Twenty (42%) patients had mutations detectable before conditioning treatment. The presence of mutations within a previously identified set of 10 gene regions before alloHCT was associated with increased rates of relapse (3-year relapse, 75% vs. 17%; P = .003) and decreased relapse-free survival (RFS; 3-year RFS, 13% vs. 49%; P = .003) in patients with MDS who received reduced intensity conditioning (RIC) vs. myeloablative conditioning (MAC).

Study details: The researchers performed targeted error-corrected DNA sequencing on preconditioning blood samples from patients with MDS (n=48) from the Blood and Marrow Transplant Clinical Trials Network 0901 phase 3 trial before random assignment to MAC (n=25) or RIC (n=23) for alloHCT.

Disclosures: This study was supported by the Intramural Research Program of the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health and by grants to the Blood and Marrow Transplant Clinical Trials Network from the NHLBI and the National Cancer Institute. The authors declared no conflicts of interest.

Source: Dillon LW et al. JCO Precis Oncol. 2021 Jan 25. doi: 10.1200/PO.20.00355.

Key clinical point: In patients with myelodysplastic syndrome (MDS) with less than 5% marrow myeloblasts and no leukemic myeloblasts in blood before allogeneic hematopoietic cell transplant (alloHCT), ultra-deep DNA sequencing for mutations in 10 gene regions previously shown to be high risk in acute myeloid leukemia could help identify which patients are likely to relapse after alloHCT.

Major finding: Twenty (42%) patients had mutations detectable before conditioning treatment. The presence of mutations within a previously identified set of 10 gene regions before alloHCT was associated with increased rates of relapse (3-year relapse, 75% vs. 17%; P = .003) and decreased relapse-free survival (RFS; 3-year RFS, 13% vs. 49%; P = .003) in patients with MDS who received reduced intensity conditioning (RIC) vs. myeloablative conditioning (MAC).

Study details: The researchers performed targeted error-corrected DNA sequencing on preconditioning blood samples from patients with MDS (n=48) from the Blood and Marrow Transplant Clinical Trials Network 0901 phase 3 trial before random assignment to MAC (n=25) or RIC (n=23) for alloHCT.

Disclosures: This study was supported by the Intramural Research Program of the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health and by grants to the Blood and Marrow Transplant Clinical Trials Network from the NHLBI and the National Cancer Institute. The authors declared no conflicts of interest.

Source: Dillon LW et al. JCO Precis Oncol. 2021 Jan 25. doi: 10.1200/PO.20.00355.

Key clinical point: In patients with myelodysplastic syndrome (MDS) with less than 5% marrow myeloblasts and no leukemic myeloblasts in blood before allogeneic hematopoietic cell transplant (alloHCT), ultra-deep DNA sequencing for mutations in 10 gene regions previously shown to be high risk in acute myeloid leukemia could help identify which patients are likely to relapse after alloHCT.

Major finding: Twenty (42%) patients had mutations detectable before conditioning treatment. The presence of mutations within a previously identified set of 10 gene regions before alloHCT was associated with increased rates of relapse (3-year relapse, 75% vs. 17%; P = .003) and decreased relapse-free survival (RFS; 3-year RFS, 13% vs. 49%; P = .003) in patients with MDS who received reduced intensity conditioning (RIC) vs. myeloablative conditioning (MAC).

Study details: The researchers performed targeted error-corrected DNA sequencing on preconditioning blood samples from patients with MDS (n=48) from the Blood and Marrow Transplant Clinical Trials Network 0901 phase 3 trial before random assignment to MAC (n=25) or RIC (n=23) for alloHCT.

Disclosures: This study was supported by the Intramural Research Program of the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health and by grants to the Blood and Marrow Transplant Clinical Trials Network from the NHLBI and the National Cancer Institute. The authors declared no conflicts of interest.

Source: Dillon LW et al. JCO Precis Oncol. 2021 Jan 25. doi: 10.1200/PO.20.00355.

Key clinical point: Eprenetapopt in combination with azacitidine yielded high rates of clinical response and complete remission (CR) and was well tolerated in patients with TP53-mutant myelodysplastic syndromes (MDS).

Major finding: Overall response rate in patients with MDS was 73% (95% confidence, [CI], 56%-85%) with 50% (95% CI, 34%-66%) of patients achieving CR. The median time to first response and CR was 1.9 and 3.1 months, respectively. Adverse events were similar to those reported for azacitidine or eprenetapopt monotherapies.

Study details: Findings come from a phase 1b/2 open-label, dose-escalation/expansion study that assessed safety, recommended dose, and efficacy of eprenetapopt and azacitidine combination in 55 patients with TP53-mutant MDS (n=40) or acute myeloid leukemia with 20%-30% marrow blasts.

Disclosures: The study was supported by the MDS Foundation Young Investigator Grant, the Early Career Award of the Dresner Foundation (DAS), and the Edward P. Evans MDS Clinical Research Consortium. The study was supported in part by the Flow Cytometry and Molecular Genomics Core Facilities at the H. Lee Moffitt Cancer Center & Research Institute. Some of the authors reported relationships with various pharmaceutical companies while some others declared no conflicts of interest.

Source: Sallman DA et al. J Clin Oncol. 2021 Jan 15. doi: 10.1200/JCO.20.02341.

Key clinical point: Eprenetapopt in combination with azacitidine yielded high rates of clinical response and complete remission (CR) and was well tolerated in patients with TP53-mutant myelodysplastic syndromes (MDS).

Major finding: Overall response rate in patients with MDS was 73% (95% confidence, [CI], 56%-85%) with 50% (95% CI, 34%-66%) of patients achieving CR. The median time to first response and CR was 1.9 and 3.1 months, respectively. Adverse events were similar to those reported for azacitidine or eprenetapopt monotherapies.

Study details: Findings come from a phase 1b/2 open-label, dose-escalation/expansion study that assessed safety, recommended dose, and efficacy of eprenetapopt and azacitidine combination in 55 patients with TP53-mutant MDS (n=40) or acute myeloid leukemia with 20%-30% marrow blasts.

Disclosures: The study was supported by the MDS Foundation Young Investigator Grant, the Early Career Award of the Dresner Foundation (DAS), and the Edward P. Evans MDS Clinical Research Consortium. The study was supported in part by the Flow Cytometry and Molecular Genomics Core Facilities at the H. Lee Moffitt Cancer Center & Research Institute. Some of the authors reported relationships with various pharmaceutical companies while some others declared no conflicts of interest.

Source: Sallman DA et al. J Clin Oncol. 2021 Jan 15. doi: 10.1200/JCO.20.02341.

Key clinical point: Eprenetapopt in combination with azacitidine yielded high rates of clinical response and complete remission (CR) and was well tolerated in patients with TP53-mutant myelodysplastic syndromes (MDS).

Major finding: Overall response rate in patients with MDS was 73% (95% confidence, [CI], 56%-85%) with 50% (95% CI, 34%-66%) of patients achieving CR. The median time to first response and CR was 1.9 and 3.1 months, respectively. Adverse events were similar to those reported for azacitidine or eprenetapopt monotherapies.

Study details: Findings come from a phase 1b/2 open-label, dose-escalation/expansion study that assessed safety, recommended dose, and efficacy of eprenetapopt and azacitidine combination in 55 patients with TP53-mutant MDS (n=40) or acute myeloid leukemia with 20%-30% marrow blasts.

Disclosures: The study was supported by the MDS Foundation Young Investigator Grant, the Early Career Award of the Dresner Foundation (DAS), and the Edward P. Evans MDS Clinical Research Consortium. The study was supported in part by the Flow Cytometry and Molecular Genomics Core Facilities at the H. Lee Moffitt Cancer Center & Research Institute. Some of the authors reported relationships with various pharmaceutical companies while some others declared no conflicts of interest.

Source: Sallman DA et al. J Clin Oncol. 2021 Jan 15. doi: 10.1200/JCO.20.02341.

A novel T-cell engineered product, Orca-T (Orca Bio), was associated with lower incidence of both acute and chronic graft-versus-host disease (GVHD) and more than double the rate of GVHD-free and relapse-free survival, compared with the current standard of care for patients undergoing hematopoietic stem cell transplants (HSCT), investigators said.

In both a multicenter phase 1 trial (NCT04013685) and single-center phase 1/2 trial (NCT01660607) with a total of 50 patients, those who received Orca-T with single-agent GVHD prophylaxis had a 1-year GVHD-free and relapse-free survival rate of 75%, compared with 31% for patients who received standard of care with two-agent prophylaxis, reported Everett H. Meyer, MD, PhD, from the Stanford (Calif.) University.

“Orca-T has good evidence for reduced acute graft-versus-host disease, reduced chromic graft-versus-host disease, and a low nonrelapse mortality,” he said at the Transplant & Cellular Therapies Meetings.

The product can be quickly manufactured and delivered to treatment centers across the continental United States, with “vein-to-vein” time of less than 72 hours, he said at the meeting held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research.

Orca-T consists of highly purified, donor-derived T-regulatory (Treg) cells that are sorted and delivered on day 0 with hematopoietic stem cells, without immunosuppressants, followed 2 days later with infusion of a matching dose of conventional T cells.

“The Treg cells are allowed to expand to create the right microenvironment for the [conventional T cells],” he explained.

In preclinical studies, donor-derived, high-purity Tregs delivered prior to adoptive transfer of conventional T cells prevented GVHD while maintaining graft-versus-tumor immunity, he said.
 

Two T-cell infusions

He reported updated results from current studies on a total of 50 adults, with a cohort of 144 patients treated concurrently with standard of care as controls.

The Orca-T–treated patients had a median age of 47 and 52% were male. Indications for transplant included acute myeloid and acute lymphoblastic leukemia, chronic myeloid leukemia, B-cell lymphoma, myelodysplastic syndrome/myelofibrosis, and other unspecified indications.

In both the Orca-T and control cohorts, patients underwent myeloablative conditioning from 10 to 2 days prior to stem cell infusion.

As noted patients in the experimental arm received infusion of hematopoietic stem/progenitor cells and Tregs, followed 2 days later by conventional T-cell infusion, and, on the day after that, tacrolimus at a target dose of 4.6 ng/mL. The conventional T cells were reserved from donor apheresis and were otherwise unmanipulated prior to infusion into the recipient, Dr. Meyer noted.

Patients in the standard-of-care arm received tacrolimus on the day before standard infusion of the apheresis product, followed by methotrexate prophylaxis on days 1, 3, 6 and 11.

Time to neutrophil engraftment, platelet engraftment, and from day 0 to hospital discharge were all significantly shorter in the Orca-T group, at 12 versus 14 days (P < .0001), 11 vs. 17 days (P < .0001), and 15 vs. 17 days (P = .01) respectively.

At 100 days of follow-up, the rate of grade 2 or greater acute GVHD was 30% among standard-of-care patients versus 10% among Orca-T–treated patients. At 1-year follow-up, respective rates of chronic GVHD were 46% vs. 3%.
 

Safety

“In general, the protocol is extremely well tolerated by our patients. We’ve seen no exceptional infectious disease complications, and we’ve seen no other major complications,” Dr. Meyer said.

Cytomegalovirus prophylaxis was used variably, depending on the center and on the attending physician. Epstein-Barr virus reactivation occurred in eight patients, with one requiring therapy, but there was no biopsy or radiographic evidence of posttransplant lymphoproliferative disorder.

In all, 18% of patients had serious adverse events during the reporting period, all of which resolved. There were no treatment-related deaths in the Orca-T arm, compared with 11% of controls.
 

Engraftment differences explored

In the question-and-answer session following the presentation, Christopher J. Gamper, MD, PhD, from the Johns Hopkins Hospital in Baltimore, told Dr. Meyer that “your outcomes from Orca-T look excellent,” and asked about the cost differential, compared with similar, unmanipulated transplants performed with standard GVHD prophylaxis.

“Is this recovered by lower costs for treatment of GVHD?” he asked.

“I have not done an economic cost analysis of course, and I think others may be looking into this,” Dr. Meyer replied. “Graft engineering can be expensive, although it’s an engineering proposition and one could imagine that the costs will go down substantially over time.”

Session moderator Alan Hanash, MD, PhD, from Memorial Sloan Kettering Cancer Center in New York, commented on the differences in engraftment between the experimental controls arms, and asked Dr. Meyer: “Do you think this is due to the difference in prophylaxis? Absence of methotrexate? Do you think that it could be a direct impact of regulatory T cells on hematopoietic engraftment?”

“Certainly not having methotrexate is beneficial for engraftment, and may account for the differences we see, Dr. Meyer said. “However, it is possible that Tregs could be playing a facilitative role. There certainly is good preclinical literature that Tregs, particularly in the bone marrow space, can facilitate bone marrow engraftment.”

The Orca-T trials are sponsored by Orca Bio and Stanford, with support from the National Institutes of Health. Dr. Meyer receives research support from Orca and is a scientific adviser to GigaGen, Triursus, Incyte, and Indee Labs. Dr. Hanash and Dr. Gamper had no relevant disclosures.

A novel T-cell engineered product, Orca-T (Orca Bio), was associated with lower incidence of both acute and chronic graft-versus-host disease (GVHD) and more than double the rate of GVHD-free and relapse-free survival, compared with the current standard of care for patients undergoing hematopoietic stem cell transplants (HSCT), investigators said.

In both a multicenter phase 1 trial (NCT04013685) and single-center phase 1/2 trial (NCT01660607) with a total of 50 patients, those who received Orca-T with single-agent GVHD prophylaxis had a 1-year GVHD-free and relapse-free survival rate of 75%, compared with 31% for patients who received standard of care with two-agent prophylaxis, reported Everett H. Meyer, MD, PhD, from the Stanford (Calif.) University.

“Orca-T has good evidence for reduced acute graft-versus-host disease, reduced chromic graft-versus-host disease, and a low nonrelapse mortality,” he said at the Transplant & Cellular Therapies Meetings.

The product can be quickly manufactured and delivered to treatment centers across the continental United States, with “vein-to-vein” time of less than 72 hours, he said at the meeting held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research.

Orca-T consists of highly purified, donor-derived T-regulatory (Treg) cells that are sorted and delivered on day 0 with hematopoietic stem cells, without immunosuppressants, followed 2 days later with infusion of a matching dose of conventional T cells.

“The Treg cells are allowed to expand to create the right microenvironment for the [conventional T cells],” he explained.

In preclinical studies, donor-derived, high-purity Tregs delivered prior to adoptive transfer of conventional T cells prevented GVHD while maintaining graft-versus-tumor immunity, he said.
 

Two T-cell infusions

He reported updated results from current studies on a total of 50 adults, with a cohort of 144 patients treated concurrently with standard of care as controls.

The Orca-T–treated patients had a median age of 47 and 52% were male. Indications for transplant included acute myeloid and acute lymphoblastic leukemia, chronic myeloid leukemia, B-cell lymphoma, myelodysplastic syndrome/myelofibrosis, and other unspecified indications.

In both the Orca-T and control cohorts, patients underwent myeloablative conditioning from 10 to 2 days prior to stem cell infusion.

As noted patients in the experimental arm received infusion of hematopoietic stem/progenitor cells and Tregs, followed 2 days later by conventional T-cell infusion, and, on the day after that, tacrolimus at a target dose of 4.6 ng/mL. The conventional T cells were reserved from donor apheresis and were otherwise unmanipulated prior to infusion into the recipient, Dr. Meyer noted.

Patients in the standard-of-care arm received tacrolimus on the day before standard infusion of the apheresis product, followed by methotrexate prophylaxis on days 1, 3, 6 and 11.

Time to neutrophil engraftment, platelet engraftment, and from day 0 to hospital discharge were all significantly shorter in the Orca-T group, at 12 versus 14 days (P < .0001), 11 vs. 17 days (P < .0001), and 15 vs. 17 days (P = .01) respectively.

At 100 days of follow-up, the rate of grade 2 or greater acute GVHD was 30% among standard-of-care patients versus 10% among Orca-T–treated patients. At 1-year follow-up, respective rates of chronic GVHD were 46% vs. 3%.
 

Safety

“In general, the protocol is extremely well tolerated by our patients. We’ve seen no exceptional infectious disease complications, and we’ve seen no other major complications,” Dr. Meyer said.

Cytomegalovirus prophylaxis was used variably, depending on the center and on the attending physician. Epstein-Barr virus reactivation occurred in eight patients, with one requiring therapy, but there was no biopsy or radiographic evidence of posttransplant lymphoproliferative disorder.

In all, 18% of patients had serious adverse events during the reporting period, all of which resolved. There were no treatment-related deaths in the Orca-T arm, compared with 11% of controls.
 

Engraftment differences explored

In the question-and-answer session following the presentation, Christopher J. Gamper, MD, PhD, from the Johns Hopkins Hospital in Baltimore, told Dr. Meyer that “your outcomes from Orca-T look excellent,” and asked about the cost differential, compared with similar, unmanipulated transplants performed with standard GVHD prophylaxis.

“Is this recovered by lower costs for treatment of GVHD?” he asked.

“I have not done an economic cost analysis of course, and I think others may be looking into this,” Dr. Meyer replied. “Graft engineering can be expensive, although it’s an engineering proposition and one could imagine that the costs will go down substantially over time.”

Session moderator Alan Hanash, MD, PhD, from Memorial Sloan Kettering Cancer Center in New York, commented on the differences in engraftment between the experimental controls arms, and asked Dr. Meyer: “Do you think this is due to the difference in prophylaxis? Absence of methotrexate? Do you think that it could be a direct impact of regulatory T cells on hematopoietic engraftment?”

“Certainly not having methotrexate is beneficial for engraftment, and may account for the differences we see, Dr. Meyer said. “However, it is possible that Tregs could be playing a facilitative role. There certainly is good preclinical literature that Tregs, particularly in the bone marrow space, can facilitate bone marrow engraftment.”

The Orca-T trials are sponsored by Orca Bio and Stanford, with support from the National Institutes of Health. Dr. Meyer receives research support from Orca and is a scientific adviser to GigaGen, Triursus, Incyte, and Indee Labs. Dr. Hanash and Dr. Gamper had no relevant disclosures.

A novel T-cell engineered product, Orca-T (Orca Bio), was associated with lower incidence of both acute and chronic graft-versus-host disease (GVHD) and more than double the rate of GVHD-free and relapse-free survival, compared with the current standard of care for patients undergoing hematopoietic stem cell transplants (HSCT), investigators said.

In both a multicenter phase 1 trial (NCT04013685) and single-center phase 1/2 trial (NCT01660607) with a total of 50 patients, those who received Orca-T with single-agent GVHD prophylaxis had a 1-year GVHD-free and relapse-free survival rate of 75%, compared with 31% for patients who received standard of care with two-agent prophylaxis, reported Everett H. Meyer, MD, PhD, from the Stanford (Calif.) University.

“Orca-T has good evidence for reduced acute graft-versus-host disease, reduced chromic graft-versus-host disease, and a low nonrelapse mortality,” he said at the Transplant & Cellular Therapies Meetings.

The product can be quickly manufactured and delivered to treatment centers across the continental United States, with “vein-to-vein” time of less than 72 hours, he said at the meeting held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research.

Orca-T consists of highly purified, donor-derived T-regulatory (Treg) cells that are sorted and delivered on day 0 with hematopoietic stem cells, without immunosuppressants, followed 2 days later with infusion of a matching dose of conventional T cells.

“The Treg cells are allowed to expand to create the right microenvironment for the [conventional T cells],” he explained.

In preclinical studies, donor-derived, high-purity Tregs delivered prior to adoptive transfer of conventional T cells prevented GVHD while maintaining graft-versus-tumor immunity, he said.
 

Two T-cell infusions

He reported updated results from current studies on a total of 50 adults, with a cohort of 144 patients treated concurrently with standard of care as controls.

The Orca-T–treated patients had a median age of 47 and 52% were male. Indications for transplant included acute myeloid and acute lymphoblastic leukemia, chronic myeloid leukemia, B-cell lymphoma, myelodysplastic syndrome/myelofibrosis, and other unspecified indications.

In both the Orca-T and control cohorts, patients underwent myeloablative conditioning from 10 to 2 days prior to stem cell infusion.

As noted patients in the experimental arm received infusion of hematopoietic stem/progenitor cells and Tregs, followed 2 days later by conventional T-cell infusion, and, on the day after that, tacrolimus at a target dose of 4.6 ng/mL. The conventional T cells were reserved from donor apheresis and were otherwise unmanipulated prior to infusion into the recipient, Dr. Meyer noted.

Patients in the standard-of-care arm received tacrolimus on the day before standard infusion of the apheresis product, followed by methotrexate prophylaxis on days 1, 3, 6 and 11.

Time to neutrophil engraftment, platelet engraftment, and from day 0 to hospital discharge were all significantly shorter in the Orca-T group, at 12 versus 14 days (P < .0001), 11 vs. 17 days (P < .0001), and 15 vs. 17 days (P = .01) respectively.

At 100 days of follow-up, the rate of grade 2 or greater acute GVHD was 30% among standard-of-care patients versus 10% among Orca-T–treated patients. At 1-year follow-up, respective rates of chronic GVHD were 46% vs. 3%.
 

Safety

“In general, the protocol is extremely well tolerated by our patients. We’ve seen no exceptional infectious disease complications, and we’ve seen no other major complications,” Dr. Meyer said.

Cytomegalovirus prophylaxis was used variably, depending on the center and on the attending physician. Epstein-Barr virus reactivation occurred in eight patients, with one requiring therapy, but there was no biopsy or radiographic evidence of posttransplant lymphoproliferative disorder.

In all, 18% of patients had serious adverse events during the reporting period, all of which resolved. There were no treatment-related deaths in the Orca-T arm, compared with 11% of controls.
 

Engraftment differences explored

In the question-and-answer session following the presentation, Christopher J. Gamper, MD, PhD, from the Johns Hopkins Hospital in Baltimore, told Dr. Meyer that “your outcomes from Orca-T look excellent,” and asked about the cost differential, compared with similar, unmanipulated transplants performed with standard GVHD prophylaxis.

“Is this recovered by lower costs for treatment of GVHD?” he asked.

“I have not done an economic cost analysis of course, and I think others may be looking into this,” Dr. Meyer replied. “Graft engineering can be expensive, although it’s an engineering proposition and one could imagine that the costs will go down substantially over time.”

Session moderator Alan Hanash, MD, PhD, from Memorial Sloan Kettering Cancer Center in New York, commented on the differences in engraftment between the experimental controls arms, and asked Dr. Meyer: “Do you think this is due to the difference in prophylaxis? Absence of methotrexate? Do you think that it could be a direct impact of regulatory T cells on hematopoietic engraftment?”

“Certainly not having methotrexate is beneficial for engraftment, and may account for the differences we see, Dr. Meyer said. “However, it is possible that Tregs could be playing a facilitative role. There certainly is good preclinical literature that Tregs, particularly in the bone marrow space, can facilitate bone marrow engraftment.”

The Orca-T trials are sponsored by Orca Bio and Stanford, with support from the National Institutes of Health. Dr. Meyer receives research support from Orca and is a scientific adviser to GigaGen, Triursus, Incyte, and Indee Labs. Dr. Hanash and Dr. Gamper had no relevant disclosures.