Key clinical point: Over 13 years of observation reveals the presence of comorbidities, including a prior malignancy, in majority of patients with myelodysplastic syndrome (MDS). A combination of comorbidities was significantly associated with worse overall survival (OS).

Major finding: A comorbidity was reported in 67% of patients, of which 24.4% had a prior malignancy. Patients with Charlson Comorbidity Index score of 4 or higher vs. lower score had significantly impaired OS (P less than .01). Both therapy-related (hazard ratio [HR], 1.51) and secondary (HR, 1.58) vs. de novo MDS were associated with worse OS (P = .04).

Study details: Data come from an observational population-based study of 291 patients with newly diagnosed MDS.

Disclosures: No source of funding was declared. The lead author reported receiving financial support from Celgene for attending the MDS Foundation meeting in 2019. The remaining authors declared no competing financial interests.

Source: Rozema J et al. Blood Adv. 2021 Mar 3. doi: 10.1182/bloodadvances.2020003381.

Key clinical point: Over 13 years of observation reveals the presence of comorbidities, including a prior malignancy, in majority of patients with myelodysplastic syndrome (MDS). A combination of comorbidities was significantly associated with worse overall survival (OS).

Major finding: A comorbidity was reported in 67% of patients, of which 24.4% had a prior malignancy. Patients with Charlson Comorbidity Index score of 4 or higher vs. lower score had significantly impaired OS (P less than .01). Both therapy-related (hazard ratio [HR], 1.51) and secondary (HR, 1.58) vs. de novo MDS were associated with worse OS (P = .04).

Study details: Data come from an observational population-based study of 291 patients with newly diagnosed MDS.

Disclosures: No source of funding was declared. The lead author reported receiving financial support from Celgene for attending the MDS Foundation meeting in 2019. The remaining authors declared no competing financial interests.

Source: Rozema J et al. Blood Adv. 2021 Mar 3. doi: 10.1182/bloodadvances.2020003381.

Key clinical point: Over 13 years of observation reveals the presence of comorbidities, including a prior malignancy, in majority of patients with myelodysplastic syndrome (MDS). A combination of comorbidities was significantly associated with worse overall survival (OS).

Major finding: A comorbidity was reported in 67% of patients, of which 24.4% had a prior malignancy. Patients with Charlson Comorbidity Index score of 4 or higher vs. lower score had significantly impaired OS (P less than .01). Both therapy-related (hazard ratio [HR], 1.51) and secondary (HR, 1.58) vs. de novo MDS were associated with worse OS (P = .04).

Study details: Data come from an observational population-based study of 291 patients with newly diagnosed MDS.

Disclosures: No source of funding was declared. The lead author reported receiving financial support from Celgene for attending the MDS Foundation meeting in 2019. The remaining authors declared no competing financial interests.

Source: Rozema J et al. Blood Adv. 2021 Mar 3. doi: 10.1182/bloodadvances.2020003381.

Key clinical point: Evolutionary Action score (EAp53), a mutation-dependent, stable predictive biomarker, can help identify prognostic subsets within TP53-mutated myelodysplastic syndrome (MDS).

Major finding: High (more than 52) vs. low (52 or lesser) EAp53 score predicted worse overall survival (10 vs. 47.8 months; P = .01). Frequency of TP53 mutations (P = .027) and multi-allelic TP53 alterations (P = .0087) was higher in high-EAp53-MDS, whereas cytogenetic abnormalities (P = .019), complex karyotype (P = .0241), and monosomal karyotype (P = .0043) were lower in low-EAp53-MDS.

Study details: Findings are from a retrospective study of 270 patients with newly diagnosed MDS or oligoblastic acute myeloid leukemia (AML; less than 30% blasts) with 1 or more missense TP53 mutation.

Disclosures: This study was partly supported by institutional start-up funds, research grant awarded to the lead author, University of Texas MD Anderson Cancer Center Support grant, and generous philanthropic donations to the University of Texas MD Anderson MDS/AML Moon Shot Program. Some of the authors declared advisory roles with; consultancies with; research support, honoraria, personal fees, and/or equity ownership from various pharmaceutical companies.

Source: Kanagal-Shamanna R et al. Blood Cancer J. 2021 Mar 6. doi: 10.1038/s41408-021-00446-y.

Key clinical point: Evolutionary Action score (EAp53), a mutation-dependent, stable predictive biomarker, can help identify prognostic subsets within TP53-mutated myelodysplastic syndrome (MDS).

Major finding: High (more than 52) vs. low (52 or lesser) EAp53 score predicted worse overall survival (10 vs. 47.8 months; P = .01). Frequency of TP53 mutations (P = .027) and multi-allelic TP53 alterations (P = .0087) was higher in high-EAp53-MDS, whereas cytogenetic abnormalities (P = .019), complex karyotype (P = .0241), and monosomal karyotype (P = .0043) were lower in low-EAp53-MDS.

Study details: Findings are from a retrospective study of 270 patients with newly diagnosed MDS or oligoblastic acute myeloid leukemia (AML; less than 30% blasts) with 1 or more missense TP53 mutation.

Disclosures: This study was partly supported by institutional start-up funds, research grant awarded to the lead author, University of Texas MD Anderson Cancer Center Support grant, and generous philanthropic donations to the University of Texas MD Anderson MDS/AML Moon Shot Program. Some of the authors declared advisory roles with; consultancies with; research support, honoraria, personal fees, and/or equity ownership from various pharmaceutical companies.

Source: Kanagal-Shamanna R et al. Blood Cancer J. 2021 Mar 6. doi: 10.1038/s41408-021-00446-y.

Key clinical point: Evolutionary Action score (EAp53), a mutation-dependent, stable predictive biomarker, can help identify prognostic subsets within TP53-mutated myelodysplastic syndrome (MDS).

Major finding: High (more than 52) vs. low (52 or lesser) EAp53 score predicted worse overall survival (10 vs. 47.8 months; P = .01). Frequency of TP53 mutations (P = .027) and multi-allelic TP53 alterations (P = .0087) was higher in high-EAp53-MDS, whereas cytogenetic abnormalities (P = .019), complex karyotype (P = .0241), and monosomal karyotype (P = .0043) were lower in low-EAp53-MDS.

Study details: Findings are from a retrospective study of 270 patients with newly diagnosed MDS or oligoblastic acute myeloid leukemia (AML; less than 30% blasts) with 1 or more missense TP53 mutation.

Disclosures: This study was partly supported by institutional start-up funds, research grant awarded to the lead author, University of Texas MD Anderson Cancer Center Support grant, and generous philanthropic donations to the University of Texas MD Anderson MDS/AML Moon Shot Program. Some of the authors declared advisory roles with; consultancies with; research support, honoraria, personal fees, and/or equity ownership from various pharmaceutical companies.

Source: Kanagal-Shamanna R et al. Blood Cancer J. 2021 Mar 6. doi: 10.1038/s41408-021-00446-y.

Key clinical point: Single-nucleotide polymorphism array (SNP-A)-based whole genome sequencing capable of detecting uniparental disomy (UPD) offers more diagnostic and prognostic information than conventional metaphase cytogenetic analysis (MC) in patients with myelodysplastic syndrome (MDS).

Major finding: SNP-A had a higher positivity for significant chromosomal aberrations than MC (58.2% vs. 36.9%; P less than .05). SNP-A detected 78 chromosomal alterations including 38 UPDs that were undetected by MC in 40 patients. Additionally, patients with vs. without UPD had a worse prognosis (P = .01).

Study details: Data come from a comparative analysis of SNP-A and MC in 127 patients with MDS (n=110) and related diseases, including myelodysplastic/myeloproliferative neoplasm (n=6) and transformed acute myeloid leukemia (n=11).

Disclosures: This study received experimental research funding from the National Natural Science Foundation of China, the Sichuan Provincial Academic and Technical Leadership Support Funding Project, and Innovation Development Program of Chengdu. The authors declared no conflicts of interest.

Source: Ou Y et al. Int J Lab Hematol. 2021 Mar 2. doi: 10.1111/ijlh.13502.

Key clinical point: Single-nucleotide polymorphism array (SNP-A)-based whole genome sequencing capable of detecting uniparental disomy (UPD) offers more diagnostic and prognostic information than conventional metaphase cytogenetic analysis (MC) in patients with myelodysplastic syndrome (MDS).

Major finding: SNP-A had a higher positivity for significant chromosomal aberrations than MC (58.2% vs. 36.9%; P less than .05). SNP-A detected 78 chromosomal alterations including 38 UPDs that were undetected by MC in 40 patients. Additionally, patients with vs. without UPD had a worse prognosis (P = .01).

Study details: Data come from a comparative analysis of SNP-A and MC in 127 patients with MDS (n=110) and related diseases, including myelodysplastic/myeloproliferative neoplasm (n=6) and transformed acute myeloid leukemia (n=11).

Disclosures: This study received experimental research funding from the National Natural Science Foundation of China, the Sichuan Provincial Academic and Technical Leadership Support Funding Project, and Innovation Development Program of Chengdu. The authors declared no conflicts of interest.

Source: Ou Y et al. Int J Lab Hematol. 2021 Mar 2. doi: 10.1111/ijlh.13502.

Key clinical point: Single-nucleotide polymorphism array (SNP-A)-based whole genome sequencing capable of detecting uniparental disomy (UPD) offers more diagnostic and prognostic information than conventional metaphase cytogenetic analysis (MC) in patients with myelodysplastic syndrome (MDS).

Major finding: SNP-A had a higher positivity for significant chromosomal aberrations than MC (58.2% vs. 36.9%; P less than .05). SNP-A detected 78 chromosomal alterations including 38 UPDs that were undetected by MC in 40 patients. Additionally, patients with vs. without UPD had a worse prognosis (P = .01).

Study details: Data come from a comparative analysis of SNP-A and MC in 127 patients with MDS (n=110) and related diseases, including myelodysplastic/myeloproliferative neoplasm (n=6) and transformed acute myeloid leukemia (n=11).

Disclosures: This study received experimental research funding from the National Natural Science Foundation of China, the Sichuan Provincial Academic and Technical Leadership Support Funding Project, and Innovation Development Program of Chengdu. The authors declared no conflicts of interest.

Source: Ou Y et al. Int J Lab Hematol. 2021 Mar 2. doi: 10.1111/ijlh.13502.

Key clinical point: Real-world evidence suggests that a combination regimen of decitabine, idarubicin, and cytarabine (D-IA) was effective and well tolerated in patients with high-risk myelodysplastic syndrome (MDS) who cannot receive intensive chemotherapy.

Major finding: The overall response rate and complete remission after 2 cycles were 76.6% and 23.4%, respectively. The 2-year estimated overall survival and event-free survival rates were 31% and 18%, respectively. Most patients showed the occurrence of grade 3/4 neutropenia and thrombocytopenia.

Study details: This retrospective study evaluated 154 patients with acute myeloid leukemia or high-risk MDS ineligible for intensive chemotherapy who were prescribed D-IA regimen (decitabine 15-20 mg/m² for 1 to 3-5 days, followed by idarubicin 3 mg/m² for 5-7 days and cytarabine 30 mg/m² for 7-14 days).

Disclosures: The study was supported by the National Natural Science Foundation of China. The authors declared no potential conflicts of interest.

Source: Xu W et al. Leuk Lymphoma. 2021 Mar 7. doi: 10.1080/10428194.2021.1891230.

Key clinical point: Real-world evidence suggests that a combination regimen of decitabine, idarubicin, and cytarabine (D-IA) was effective and well tolerated in patients with high-risk myelodysplastic syndrome (MDS) who cannot receive intensive chemotherapy.

Major finding: The overall response rate and complete remission after 2 cycles were 76.6% and 23.4%, respectively. The 2-year estimated overall survival and event-free survival rates were 31% and 18%, respectively. Most patients showed the occurrence of grade 3/4 neutropenia and thrombocytopenia.

Study details: This retrospective study evaluated 154 patients with acute myeloid leukemia or high-risk MDS ineligible for intensive chemotherapy who were prescribed D-IA regimen (decitabine 15-20 mg/m² for 1 to 3-5 days, followed by idarubicin 3 mg/m² for 5-7 days and cytarabine 30 mg/m² for 7-14 days).

Disclosures: The study was supported by the National Natural Science Foundation of China. The authors declared no potential conflicts of interest.

Source: Xu W et al. Leuk Lymphoma. 2021 Mar 7. doi: 10.1080/10428194.2021.1891230.

Key clinical point: Real-world evidence suggests that a combination regimen of decitabine, idarubicin, and cytarabine (D-IA) was effective and well tolerated in patients with high-risk myelodysplastic syndrome (MDS) who cannot receive intensive chemotherapy.

Major finding: The overall response rate and complete remission after 2 cycles were 76.6% and 23.4%, respectively. The 2-year estimated overall survival and event-free survival rates were 31% and 18%, respectively. Most patients showed the occurrence of grade 3/4 neutropenia and thrombocytopenia.

Study details: This retrospective study evaluated 154 patients with acute myeloid leukemia or high-risk MDS ineligible for intensive chemotherapy who were prescribed D-IA regimen (decitabine 15-20 mg/m² for 1 to 3-5 days, followed by idarubicin 3 mg/m² for 5-7 days and cytarabine 30 mg/m² for 7-14 days).

Disclosures: The study was supported by the National Natural Science Foundation of China. The authors declared no potential conflicts of interest.

Source: Xu W et al. Leuk Lymphoma. 2021 Mar 7. doi: 10.1080/10428194.2021.1891230.

Key clinical point: Paroxysmal nocturnal hemoglobinuria (PNH) clones are highly prevalent in myelodysplastic syndrome (MDS). PNH positivity predicted higher response to immunosuppressive therapy (IST) and stem cell transplants along with a favorable impact on overall survival (OS).

Major finding: PNH clones were present in 20.3% of MDS cases. PNH-positive vs. PNH-negative patients showed significantly higher response to IST (84% vs. 44.7%; P = .01) and stem cell transplant (71% vs. 56.6%; P = .09). PNH positivity had a favorable impact on disease progression (P less than .01) and overall survival (P less than .0001).

Study details: Data come from a large single-center study involving 3,085 patients with suspected underlying myeloid disorders, cytopenia, or unexplained thrombosis who underwent a first-time PNH test. The cohort had 869 cases of MDS.

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

Source: Fattizzo B et al. Leukemia. 2021 Mar 4. doi: 10.1038/s41375-021-01190-9.

Key clinical point: Paroxysmal nocturnal hemoglobinuria (PNH) clones are highly prevalent in myelodysplastic syndrome (MDS). PNH positivity predicted higher response to immunosuppressive therapy (IST) and stem cell transplants along with a favorable impact on overall survival (OS).

Major finding: PNH clones were present in 20.3% of MDS cases. PNH-positive vs. PNH-negative patients showed significantly higher response to IST (84% vs. 44.7%; P = .01) and stem cell transplant (71% vs. 56.6%; P = .09). PNH positivity had a favorable impact on disease progression (P less than .01) and overall survival (P less than .0001).

Study details: Data come from a large single-center study involving 3,085 patients with suspected underlying myeloid disorders, cytopenia, or unexplained thrombosis who underwent a first-time PNH test. The cohort had 869 cases of MDS.

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

Source: Fattizzo B et al. Leukemia. 2021 Mar 4. doi: 10.1038/s41375-021-01190-9.

Key clinical point: Paroxysmal nocturnal hemoglobinuria (PNH) clones are highly prevalent in myelodysplastic syndrome (MDS). PNH positivity predicted higher response to immunosuppressive therapy (IST) and stem cell transplants along with a favorable impact on overall survival (OS).

Major finding: PNH clones were present in 20.3% of MDS cases. PNH-positive vs. PNH-negative patients showed significantly higher response to IST (84% vs. 44.7%; P = .01) and stem cell transplant (71% vs. 56.6%; P = .09). PNH positivity had a favorable impact on disease progression (P less than .01) and overall survival (P less than .0001).

Study details: Data come from a large single-center study involving 3,085 patients with suspected underlying myeloid disorders, cytopenia, or unexplained thrombosis who underwent a first-time PNH test. The cohort had 869 cases of MDS.

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

Source: Fattizzo B et al. Leukemia. 2021 Mar 4. doi: 10.1038/s41375-021-01190-9.

Key clinical point: Findings confirm dismal outcomes after azacitidine (AZA) discontinuation in patients with myelodysplastic syndrome (MDS); however, outcomes were best in those who discontinued AZA while being in response to undergo planned hematopoietic stem cell transplantation (HSCT).

Major finding: At discontinuation, 20.3% of the patients were still responding to AZA, 35.4% had primary resistance, and 44.3% developed adaptive resistance. Long-term survival was significantly better in patients who discontinued AZA while in response vs. those with primary or adaptive resistance (P = .004) with best outcomes in patients who discontinued to undergo planned HSCT with the median survival not reached and a 5-year survival rate of 56% (P less than .001).

Study details: This retrospective study evaluated 414 patients with MDS consecutively enrolled in the Italian MDS Registry of the Fondazione Italiana Sindromi Mielodisplastiche (FISiM) and treated with AZA.

Disclosures: FISiM received support from Celgene Corporation to carry on the analysis. Some of the authors declared receiving personal fees, grants, and/or honoraria from various pharmaceutical companies including Celgene/Bristol-Myers Squibb.

Source: Clavio M et al. Cancer. 2021 Mar 19. doi: 10.1002/cncr.33472.

Key clinical point: Findings confirm dismal outcomes after azacitidine (AZA) discontinuation in patients with myelodysplastic syndrome (MDS); however, outcomes were best in those who discontinued AZA while being in response to undergo planned hematopoietic stem cell transplantation (HSCT).

Major finding: At discontinuation, 20.3% of the patients were still responding to AZA, 35.4% had primary resistance, and 44.3% developed adaptive resistance. Long-term survival was significantly better in patients who discontinued AZA while in response vs. those with primary or adaptive resistance (P = .004) with best outcomes in patients who discontinued to undergo planned HSCT with the median survival not reached and a 5-year survival rate of 56% (P less than .001).

Study details: This retrospective study evaluated 414 patients with MDS consecutively enrolled in the Italian MDS Registry of the Fondazione Italiana Sindromi Mielodisplastiche (FISiM) and treated with AZA.

Disclosures: FISiM received support from Celgene Corporation to carry on the analysis. Some of the authors declared receiving personal fees, grants, and/or honoraria from various pharmaceutical companies including Celgene/Bristol-Myers Squibb.

Source: Clavio M et al. Cancer. 2021 Mar 19. doi: 10.1002/cncr.33472.

Key clinical point: Findings confirm dismal outcomes after azacitidine (AZA) discontinuation in patients with myelodysplastic syndrome (MDS); however, outcomes were best in those who discontinued AZA while being in response to undergo planned hematopoietic stem cell transplantation (HSCT).

Major finding: At discontinuation, 20.3% of the patients were still responding to AZA, 35.4% had primary resistance, and 44.3% developed adaptive resistance. Long-term survival was significantly better in patients who discontinued AZA while in response vs. those with primary or adaptive resistance (P = .004) with best outcomes in patients who discontinued to undergo planned HSCT with the median survival not reached and a 5-year survival rate of 56% (P less than .001).

Study details: This retrospective study evaluated 414 patients with MDS consecutively enrolled in the Italian MDS Registry of the Fondazione Italiana Sindromi Mielodisplastiche (FISiM) and treated with AZA.

Disclosures: FISiM received support from Celgene Corporation to carry on the analysis. Some of the authors declared receiving personal fees, grants, and/or honoraria from various pharmaceutical companies including Celgene/Bristol-Myers Squibb.

Source: Clavio M et al. Cancer. 2021 Mar 19. doi: 10.1002/cncr.33472.

Key clinical point: Among patients with a solid tumor, the use of poly(adenosine diphosphate-ribose) polymerase inhibitor (PARPi) was associated with an increased incidence of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) in those receiving a PARPi early in their disease course.

Major finding: Use of PARPi was associated with an increased incidence of MDS/AML in the frontline setting (incidence rate ratio [IRR], 5.43; 95% confidence interval [CI], 1.51–19.60) but not in the recurrent setting.

Study details: Findings are from a meta-analysis of 14 phase 2 and 3 clinical trials that randomly allocated 5,739 patients with solid tumors to either PARPi or control therapy.

Disclosures: This study was supported by the National Institutes of Health, National Cancer Institute, and National Center for Advancing Translational Sciences. Some of the authors declared receiving research funding, grants, and/or personal fees from various pharmaceutical companies.

Source: Nitecki R et al. Gynecol Oncol. 2021 Mar 15. doi: 10.1016/j.ygyno.2021.03.011.

Key clinical point: Among patients with a solid tumor, the use of poly(adenosine diphosphate-ribose) polymerase inhibitor (PARPi) was associated with an increased incidence of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) in those receiving a PARPi early in their disease course.

Major finding: Use of PARPi was associated with an increased incidence of MDS/AML in the frontline setting (incidence rate ratio [IRR], 5.43; 95% confidence interval [CI], 1.51–19.60) but not in the recurrent setting.

Study details: Findings are from a meta-analysis of 14 phase 2 and 3 clinical trials that randomly allocated 5,739 patients with solid tumors to either PARPi or control therapy.

Disclosures: This study was supported by the National Institutes of Health, National Cancer Institute, and National Center for Advancing Translational Sciences. Some of the authors declared receiving research funding, grants, and/or personal fees from various pharmaceutical companies.

Source: Nitecki R et al. Gynecol Oncol. 2021 Mar 15. doi: 10.1016/j.ygyno.2021.03.011.

Key clinical point: Among patients with a solid tumor, the use of poly(adenosine diphosphate-ribose) polymerase inhibitor (PARPi) was associated with an increased incidence of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) in those receiving a PARPi early in their disease course.

Major finding: Use of PARPi was associated with an increased incidence of MDS/AML in the frontline setting (incidence rate ratio [IRR], 5.43; 95% confidence interval [CI], 1.51–19.60) but not in the recurrent setting.

Study details: Findings are from a meta-analysis of 14 phase 2 and 3 clinical trials that randomly allocated 5,739 patients with solid tumors to either PARPi or control therapy.

Disclosures: This study was supported by the National Institutes of Health, National Cancer Institute, and National Center for Advancing Translational Sciences. Some of the authors declared receiving research funding, grants, and/or personal fees from various pharmaceutical companies.

Source: Nitecki R et al. Gynecol Oncol. 2021 Mar 15. doi: 10.1016/j.ygyno.2021.03.011.

Key clinical point: Red blood cell transfusion independence (TI) among patients with myelodysplastic syndrome (MDS) was associated with longer overall survival and lower risk for acute myeloid leukemia (AML) progression.

Major finding: Risk of death was 61.8% (hazard ratio [HR], 0.382; 95% credible interval [CrI], 0.201-0.666) lower in patients with TI vs. transfusion dependence (TD) and 63.4% (HR, 0.366; 95% CrI, 0.217-0.553) lower in patients who acquired TI through treatment vs. those who did not. Patients with TD vs. TI showed a trend toward worse prognosis and higher risk for AML progression (HR, 0.754; 95% CrI, 0.311-1.811).

Study details: Findings are from a meta-analysis of pooled studies that estimated the effect of transfusion sensitivity on clinical outcomes in patients with MDS.

Disclosures: The study was supported by Bristol-Myers Squibb Company. D Tang reported being an employee and equity holder of Bristol-Myers Squibb. T Schroeder reported being a consultant for Celgene International, a Bristol-Myers Squibb Company. The other authors declared no conflicts of interest.

Source: Lemos MB et al. Eur J Haematol. 2021 Mar 14. doi: 10.1111/ejh.13619.

Key clinical point: Red blood cell transfusion independence (TI) among patients with myelodysplastic syndrome (MDS) was associated with longer overall survival and lower risk for acute myeloid leukemia (AML) progression.

Major finding: Risk of death was 61.8% (hazard ratio [HR], 0.382; 95% credible interval [CrI], 0.201-0.666) lower in patients with TI vs. transfusion dependence (TD) and 63.4% (HR, 0.366; 95% CrI, 0.217-0.553) lower in patients who acquired TI through treatment vs. those who did not. Patients with TD vs. TI showed a trend toward worse prognosis and higher risk for AML progression (HR, 0.754; 95% CrI, 0.311-1.811).

Study details: Findings are from a meta-analysis of pooled studies that estimated the effect of transfusion sensitivity on clinical outcomes in patients with MDS.

Disclosures: The study was supported by Bristol-Myers Squibb Company. D Tang reported being an employee and equity holder of Bristol-Myers Squibb. T Schroeder reported being a consultant for Celgene International, a Bristol-Myers Squibb Company. The other authors declared no conflicts of interest.

Source: Lemos MB et al. Eur J Haematol. 2021 Mar 14. doi: 10.1111/ejh.13619.

Key clinical point: Red blood cell transfusion independence (TI) among patients with myelodysplastic syndrome (MDS) was associated with longer overall survival and lower risk for acute myeloid leukemia (AML) progression.

Major finding: Risk of death was 61.8% (hazard ratio [HR], 0.382; 95% credible interval [CrI], 0.201-0.666) lower in patients with TI vs. transfusion dependence (TD) and 63.4% (HR, 0.366; 95% CrI, 0.217-0.553) lower in patients who acquired TI through treatment vs. those who did not. Patients with TD vs. TI showed a trend toward worse prognosis and higher risk for AML progression (HR, 0.754; 95% CrI, 0.311-1.811).

Study details: Findings are from a meta-analysis of pooled studies that estimated the effect of transfusion sensitivity on clinical outcomes in patients with MDS.

Disclosures: The study was supported by Bristol-Myers Squibb Company. D Tang reported being an employee and equity holder of Bristol-Myers Squibb. T Schroeder reported being a consultant for Celgene International, a Bristol-Myers Squibb Company. The other authors declared no conflicts of interest.

Source: Lemos MB et al. Eur J Haematol. 2021 Mar 14. doi: 10.1111/ejh.13619.

More than 10 years after the withdrawal of the weight-loss drug Mediator (benfluorex) from the market in France, the Paris Court issued its judgment on March 29, 2021, against Servier Laboratories and the French National Agency for the Safety of Medicines and Health Products (ANSM).

Servier Laboratories was convicted of “aggravated deception” and fined 2.7 million euros (approximately $3.2 million) but were found not guilty of fraud. ANSM will also have to pay a fine.

Mediator was brought to the market in 1976 for the treatment of hyperlipidemia and for overweight patients with type 2 diabetes but was used off label as an appetite suppressant. It was taken by 5 million people and was only removed from the market in France in 2009 because of its toxic effects.

Mediator was taken off the market in Spain 6 years earlier, and in Switzerland 12 years earlier, and more than 30 years before in Belgium. It was never marketed in the United States.

The number of deaths because of heart valve damage related to the drug in France has been estimated at 220-300 in the short term (2.5 years) and 1,300-1,800 in the long term. In addition, the drug has been responsible for 3,100-4,200 hospital admissions for valvular insufficiency and pulmonary arterial hypertension.

“Despite knowing the risks for very many years ... [Servier Laboratories] never took the necessary measures and thus deceived” consumers of Mediator, declared the president of the criminal court, Sylvie Daunois.

Servier has “weakened confidence in the health system,” she added.

“I am very happy that ‘aggravated deception,’ the heart of the case, has been recognized and condemned,” Irène Frachon, MD, a pulmonologist at Brest (France) University Hospital and whistleblower on the Mediator scandal, said in an interview.

However, Dr. Frachon continued: “The major problem, putting a toxic agent on the market for years, is a given. But the weakness of the sentences gives a mixed message.

“The judgment is too cautious in its punishments,” she added, pointing out that, “in the case of contaminated blood, there were prison sentences.”
 

Servier deceived doctors and patients

The French trial in September 2019 was extraordinary, with about 100 witnesses, nearly 400 lawyers, and 5,000 victims.

On June 23, 2020, the prosecutor, Aude Le Guilcher, requested at the end of her indictment that the six companies of the Servier group be fined, notably for “deception, homicide, involuntary injuries, and fraud,” to the tune of 20.3 million euros (approximately $23.8 million).

Against the former No. 2 of Servier, Jean-Philippe Seta, Ms. Le Guilcher requested 5 years in prison, with 2 years suspended, and a 200,000 euro (approximately $235,000) fine.

The same sum was requested against ANSM for homicide and unintentional injuries.

In the end, Mr. Seta, the former right hand of Jacques Servier, who died in 2004, was sentenced to 4 years in prison, suspended. For their part, ANSM was fined 303,000 euros(approximately $350,000).

It is now clearly established that Servier Laboratories knowingly concealed the similarity of Mediator to the fenfluramine family of compounds, which was banned in 1990 because of adverse effects.

The group also deceived doctors who prescribed the drug and patients who took it by hiding its toxicity.
 

Mediator should never have been authorized for use

In terms of the fraud charges, the prosecutor estimated that the losses incurred by the primary health insurance industry were in the region of several hundred million euros.

She argued that Mediator should never have been reimbursed, as “it should never have benefited from market authorization, which it received solely due to the fraudulent actions of the company.”

But because of the statute of limitations, this argument was not heard, explained Dr. Frachon, “and the same is true of conflicts of interest, where limitations led to them being discharged.

“We understand the legal difficulties, but it’s a shame in terms of the signal sent.”

“I hope the medical world will learn the lesson and not continue with ‘business as usual’ with people who are delinquents. I think it will be essential to restore public confidence,” concluded Dr. Frachon.

No conflicts of interest or funding were declared.

A version of this article first appeared on Medscape.com.

More than 10 years after the withdrawal of the weight-loss drug Mediator (benfluorex) from the market in France, the Paris Court issued its judgment on March 29, 2021, against Servier Laboratories and the French National Agency for the Safety of Medicines and Health Products (ANSM).

Servier Laboratories was convicted of “aggravated deception” and fined 2.7 million euros (approximately $3.2 million) but were found not guilty of fraud. ANSM will also have to pay a fine.

Mediator was brought to the market in 1976 for the treatment of hyperlipidemia and for overweight patients with type 2 diabetes but was used off label as an appetite suppressant. It was taken by 5 million people and was only removed from the market in France in 2009 because of its toxic effects.

Mediator was taken off the market in Spain 6 years earlier, and in Switzerland 12 years earlier, and more than 30 years before in Belgium. It was never marketed in the United States.

The number of deaths because of heart valve damage related to the drug in France has been estimated at 220-300 in the short term (2.5 years) and 1,300-1,800 in the long term. In addition, the drug has been responsible for 3,100-4,200 hospital admissions for valvular insufficiency and pulmonary arterial hypertension.

“Despite knowing the risks for very many years ... [Servier Laboratories] never took the necessary measures and thus deceived” consumers of Mediator, declared the president of the criminal court, Sylvie Daunois.

Servier has “weakened confidence in the health system,” she added.

“I am very happy that ‘aggravated deception,’ the heart of the case, has been recognized and condemned,” Irène Frachon, MD, a pulmonologist at Brest (France) University Hospital and whistleblower on the Mediator scandal, said in an interview.

However, Dr. Frachon continued: “The major problem, putting a toxic agent on the market for years, is a given. But the weakness of the sentences gives a mixed message.

“The judgment is too cautious in its punishments,” she added, pointing out that, “in the case of contaminated blood, there were prison sentences.”
 

Servier deceived doctors and patients

The French trial in September 2019 was extraordinary, with about 100 witnesses, nearly 400 lawyers, and 5,000 victims.

On June 23, 2020, the prosecutor, Aude Le Guilcher, requested at the end of her indictment that the six companies of the Servier group be fined, notably for “deception, homicide, involuntary injuries, and fraud,” to the tune of 20.3 million euros (approximately $23.8 million).

Against the former No. 2 of Servier, Jean-Philippe Seta, Ms. Le Guilcher requested 5 years in prison, with 2 years suspended, and a 200,000 euro (approximately $235,000) fine.

The same sum was requested against ANSM for homicide and unintentional injuries.

In the end, Mr. Seta, the former right hand of Jacques Servier, who died in 2004, was sentenced to 4 years in prison, suspended. For their part, ANSM was fined 303,000 euros(approximately $350,000).

It is now clearly established that Servier Laboratories knowingly concealed the similarity of Mediator to the fenfluramine family of compounds, which was banned in 1990 because of adverse effects.

The group also deceived doctors who prescribed the drug and patients who took it by hiding its toxicity.
 

Mediator should never have been authorized for use

In terms of the fraud charges, the prosecutor estimated that the losses incurred by the primary health insurance industry were in the region of several hundred million euros.

She argued that Mediator should never have been reimbursed, as “it should never have benefited from market authorization, which it received solely due to the fraudulent actions of the company.”

But because of the statute of limitations, this argument was not heard, explained Dr. Frachon, “and the same is true of conflicts of interest, where limitations led to them being discharged.

“We understand the legal difficulties, but it’s a shame in terms of the signal sent.”

“I hope the medical world will learn the lesson and not continue with ‘business as usual’ with people who are delinquents. I think it will be essential to restore public confidence,” concluded Dr. Frachon.

No conflicts of interest or funding were declared.

A version of this article first appeared on Medscape.com.

More than 10 years after the withdrawal of the weight-loss drug Mediator (benfluorex) from the market in France, the Paris Court issued its judgment on March 29, 2021, against Servier Laboratories and the French National Agency for the Safety of Medicines and Health Products (ANSM).

Servier Laboratories was convicted of “aggravated deception” and fined 2.7 million euros (approximately $3.2 million) but were found not guilty of fraud. ANSM will also have to pay a fine.

Mediator was brought to the market in 1976 for the treatment of hyperlipidemia and for overweight patients with type 2 diabetes but was used off label as an appetite suppressant. It was taken by 5 million people and was only removed from the market in France in 2009 because of its toxic effects.

Mediator was taken off the market in Spain 6 years earlier, and in Switzerland 12 years earlier, and more than 30 years before in Belgium. It was never marketed in the United States.

The number of deaths because of heart valve damage related to the drug in France has been estimated at 220-300 in the short term (2.5 years) and 1,300-1,800 in the long term. In addition, the drug has been responsible for 3,100-4,200 hospital admissions for valvular insufficiency and pulmonary arterial hypertension.

“Despite knowing the risks for very many years ... [Servier Laboratories] never took the necessary measures and thus deceived” consumers of Mediator, declared the president of the criminal court, Sylvie Daunois.

Servier has “weakened confidence in the health system,” she added.

“I am very happy that ‘aggravated deception,’ the heart of the case, has been recognized and condemned,” Irène Frachon, MD, a pulmonologist at Brest (France) University Hospital and whistleblower on the Mediator scandal, said in an interview.

However, Dr. Frachon continued: “The major problem, putting a toxic agent on the market for years, is a given. But the weakness of the sentences gives a mixed message.

“The judgment is too cautious in its punishments,” she added, pointing out that, “in the case of contaminated blood, there were prison sentences.”
 

Servier deceived doctors and patients

The French trial in September 2019 was extraordinary, with about 100 witnesses, nearly 400 lawyers, and 5,000 victims.

On June 23, 2020, the prosecutor, Aude Le Guilcher, requested at the end of her indictment that the six companies of the Servier group be fined, notably for “deception, homicide, involuntary injuries, and fraud,” to the tune of 20.3 million euros (approximately $23.8 million).

Against the former No. 2 of Servier, Jean-Philippe Seta, Ms. Le Guilcher requested 5 years in prison, with 2 years suspended, and a 200,000 euro (approximately $235,000) fine.

The same sum was requested against ANSM for homicide and unintentional injuries.

In the end, Mr. Seta, the former right hand of Jacques Servier, who died in 2004, was sentenced to 4 years in prison, suspended. For their part, ANSM was fined 303,000 euros(approximately $350,000).

It is now clearly established that Servier Laboratories knowingly concealed the similarity of Mediator to the fenfluramine family of compounds, which was banned in 1990 because of adverse effects.

The group also deceived doctors who prescribed the drug and patients who took it by hiding its toxicity.
 

Mediator should never have been authorized for use

In terms of the fraud charges, the prosecutor estimated that the losses incurred by the primary health insurance industry were in the region of several hundred million euros.

She argued that Mediator should never have been reimbursed, as “it should never have benefited from market authorization, which it received solely due to the fraudulent actions of the company.”

But because of the statute of limitations, this argument was not heard, explained Dr. Frachon, “and the same is true of conflicts of interest, where limitations led to them being discharged.

“We understand the legal difficulties, but it’s a shame in terms of the signal sent.”

“I hope the medical world will learn the lesson and not continue with ‘business as usual’ with people who are delinquents. I think it will be essential to restore public confidence,” concluded Dr. Frachon.

No conflicts of interest or funding were declared.

A version of this article first appeared on Medscape.com.

Patients at very high risk for melanoma, including those with a family history or with inherited pathogenic variants of genes that increase the risk, likely benefit from routine whole-body screening for melanoma and education about UV protection.

Those are key findings from the first prospective cohort study to quantify the benefit of screening in melanoma-prone families, which was published online April 2 in Cancer Epidemiology, Biomarkers & Prevention.

“Whole-body screening for melanoma is currently routine for individuals at high risk for melanoma, which includes people from melanoma-prone families (at least two relatives who have had melanoma) and those with inherited pathogenic gene variants of the CDKN2A or CDK4 genes, which increase risk for melanoma,” lead author Michael R. Sargen, MD, said in an interview. “In our study, we investigated whether screening and educational interventions, including education about the appearance of melanoma and strategies for protecting skin from ultraviolet damage, contributed to early diagnosis of melanoma in individuals from melanoma-prone families.”

Of the 293 individuals who enrolled in the study between 1976 and 2014, 246 were diagnosed with melanoma before enrollment (the prestudy cohort) and 47 were diagnosed after enrollment (the prospective cohort). The researchers compared differences in melanoma thickness and tumor stage between participants in the prestudy and prospective cohorts, and compared tumor-thickness trends between participants in their study and cases in the general population using data from Surveillance, Epidemiology, and End Results (SEER) registries between 1973 and 2016. Because information on melanoma thickness was missing for 24% of melanoma cases in the NCI Familial Melanoma Study and 8.7% of melanoma cases found in the SEER registry, the researchers imputed the missing data.

After adjusting for gender and age, Dr. Sargen and his colleagues found that participants in the prospective cohort had significantly thinner melanomas, compared with those in the prestudy cohort (0.6 mm vs. 1.1 mm, respectively; P < .001). In addition, 83% of those in the prospective cohort were significantly more likely to be diagnosed at the early T1 stage, compared with 40% of those in the prestudy cohort (P < .001).

In their analysis, they also determined that after adjusting for gender and age, “all NCI family cases had systematically lower thickness than SEER cases during the study period.” The reductions in melanoma thickness and tumor stage, they concluded, “were not fully explained by calendar period effects of decreasing thickness in the general population and point to the potential benefit of skin cancer screening for patients with a family history of melanoma and those with pathogenic germline variants of melanoma-susceptibility genes.”

“Our data provide reassuring evidence that screening, alongside education about proper UV protection and the appearance of melanoma, is likely benefiting patients with a significantly elevated risk for melanoma,” Dr. Sargen said in the interview “Further studies are needed to determine whether individuals without a family history of melanoma may benefit from whole-body screening, and whether the benefits vary by ethnicity.”

He acknowledged certain limitations of the study, including the relatively small sample size of melanoma cases in the NCI Familial Melanoma Study and the imputation of missing melanoma-thickness data. “Additionally, since this was a prospective cohort study, we were not able to distinguish the independent effect of each intervention,” he said. “Randomized controlled studies are needed to understand the impact of each aspect of the intervention, such as whole-body screening, melanoma education, or strategies for skin protection.”

In an interview, Maryam M. Asgari, MD, professor of dermatology at Harvard University, Boston, called the analysis “well done,” but commented on the potential role of selection bias impacting the findings. “People who have a strong family history of melanoma and who are opting to engage in an NCI study and come in for full-body skin checks and go through that education process may have very different health-seeking behaviors than individuals in the general population that would be reported to SEER,” she said.

She also raised the question of whether the results were driven by the early detection through the NCI’s program of provider screening or through the educational component that enables earlier self-detection. “If you’re an individual involved in a study and that brings attention to your moles and you have a strong family history of melanoma to begin with, it is not surprising that you are going to have heightened awareness of any changing mole and therefore are more likely to have melanoma detected at an earlier stage,” Dr. Asgari said.

The study was supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics at the National Cancer Institute. Dr. Sargen reported having no financial disclosures.
Dr. Asgari disclosed that she has received research support from the Melanoma Research Alliance.
 

[email protected]

Patients at very high risk for melanoma, including those with a family history or with inherited pathogenic variants of genes that increase the risk, likely benefit from routine whole-body screening for melanoma and education about UV protection.

Those are key findings from the first prospective cohort study to quantify the benefit of screening in melanoma-prone families, which was published online April 2 in Cancer Epidemiology, Biomarkers & Prevention.

“Whole-body screening for melanoma is currently routine for individuals at high risk for melanoma, which includes people from melanoma-prone families (at least two relatives who have had melanoma) and those with inherited pathogenic gene variants of the CDKN2A or CDK4 genes, which increase risk for melanoma,” lead author Michael R. Sargen, MD, said in an interview. “In our study, we investigated whether screening and educational interventions, including education about the appearance of melanoma and strategies for protecting skin from ultraviolet damage, contributed to early diagnosis of melanoma in individuals from melanoma-prone families.”

Of the 293 individuals who enrolled in the study between 1976 and 2014, 246 were diagnosed with melanoma before enrollment (the prestudy cohort) and 47 were diagnosed after enrollment (the prospective cohort). The researchers compared differences in melanoma thickness and tumor stage between participants in the prestudy and prospective cohorts, and compared tumor-thickness trends between participants in their study and cases in the general population using data from Surveillance, Epidemiology, and End Results (SEER) registries between 1973 and 2016. Because information on melanoma thickness was missing for 24% of melanoma cases in the NCI Familial Melanoma Study and 8.7% of melanoma cases found in the SEER registry, the researchers imputed the missing data.

After adjusting for gender and age, Dr. Sargen and his colleagues found that participants in the prospective cohort had significantly thinner melanomas, compared with those in the prestudy cohort (0.6 mm vs. 1.1 mm, respectively; P < .001). In addition, 83% of those in the prospective cohort were significantly more likely to be diagnosed at the early T1 stage, compared with 40% of those in the prestudy cohort (P < .001).

In their analysis, they also determined that after adjusting for gender and age, “all NCI family cases had systematically lower thickness than SEER cases during the study period.” The reductions in melanoma thickness and tumor stage, they concluded, “were not fully explained by calendar period effects of decreasing thickness in the general population and point to the potential benefit of skin cancer screening for patients with a family history of melanoma and those with pathogenic germline variants of melanoma-susceptibility genes.”

“Our data provide reassuring evidence that screening, alongside education about proper UV protection and the appearance of melanoma, is likely benefiting patients with a significantly elevated risk for melanoma,” Dr. Sargen said in the interview “Further studies are needed to determine whether individuals without a family history of melanoma may benefit from whole-body screening, and whether the benefits vary by ethnicity.”

He acknowledged certain limitations of the study, including the relatively small sample size of melanoma cases in the NCI Familial Melanoma Study and the imputation of missing melanoma-thickness data. “Additionally, since this was a prospective cohort study, we were not able to distinguish the independent effect of each intervention,” he said. “Randomized controlled studies are needed to understand the impact of each aspect of the intervention, such as whole-body screening, melanoma education, or strategies for skin protection.”

In an interview, Maryam M. Asgari, MD, professor of dermatology at Harvard University, Boston, called the analysis “well done,” but commented on the potential role of selection bias impacting the findings. “People who have a strong family history of melanoma and who are opting to engage in an NCI study and come in for full-body skin checks and go through that education process may have very different health-seeking behaviors than individuals in the general population that would be reported to SEER,” she said.

She also raised the question of whether the results were driven by the early detection through the NCI’s program of provider screening or through the educational component that enables earlier self-detection. “If you’re an individual involved in a study and that brings attention to your moles and you have a strong family history of melanoma to begin with, it is not surprising that you are going to have heightened awareness of any changing mole and therefore are more likely to have melanoma detected at an earlier stage,” Dr. Asgari said.

The study was supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics at the National Cancer Institute. Dr. Sargen reported having no financial disclosures.
Dr. Asgari disclosed that she has received research support from the Melanoma Research Alliance.
 

[email protected]

Patients at very high risk for melanoma, including those with a family history or with inherited pathogenic variants of genes that increase the risk, likely benefit from routine whole-body screening for melanoma and education about UV protection.

Those are key findings from the first prospective cohort study to quantify the benefit of screening in melanoma-prone families, which was published online April 2 in Cancer Epidemiology, Biomarkers & Prevention.

“Whole-body screening for melanoma is currently routine for individuals at high risk for melanoma, which includes people from melanoma-prone families (at least two relatives who have had melanoma) and those with inherited pathogenic gene variants of the CDKN2A or CDK4 genes, which increase risk for melanoma,” lead author Michael R. Sargen, MD, said in an interview. “In our study, we investigated whether screening and educational interventions, including education about the appearance of melanoma and strategies for protecting skin from ultraviolet damage, contributed to early diagnosis of melanoma in individuals from melanoma-prone families.”

Of the 293 individuals who enrolled in the study between 1976 and 2014, 246 were diagnosed with melanoma before enrollment (the prestudy cohort) and 47 were diagnosed after enrollment (the prospective cohort). The researchers compared differences in melanoma thickness and tumor stage between participants in the prestudy and prospective cohorts, and compared tumor-thickness trends between participants in their study and cases in the general population using data from Surveillance, Epidemiology, and End Results (SEER) registries between 1973 and 2016. Because information on melanoma thickness was missing for 24% of melanoma cases in the NCI Familial Melanoma Study and 8.7% of melanoma cases found in the SEER registry, the researchers imputed the missing data.

After adjusting for gender and age, Dr. Sargen and his colleagues found that participants in the prospective cohort had significantly thinner melanomas, compared with those in the prestudy cohort (0.6 mm vs. 1.1 mm, respectively; P < .001). In addition, 83% of those in the prospective cohort were significantly more likely to be diagnosed at the early T1 stage, compared with 40% of those in the prestudy cohort (P < .001).

In their analysis, they also determined that after adjusting for gender and age, “all NCI family cases had systematically lower thickness than SEER cases during the study period.” The reductions in melanoma thickness and tumor stage, they concluded, “were not fully explained by calendar period effects of decreasing thickness in the general population and point to the potential benefit of skin cancer screening for patients with a family history of melanoma and those with pathogenic germline variants of melanoma-susceptibility genes.”

“Our data provide reassuring evidence that screening, alongside education about proper UV protection and the appearance of melanoma, is likely benefiting patients with a significantly elevated risk for melanoma,” Dr. Sargen said in the interview “Further studies are needed to determine whether individuals without a family history of melanoma may benefit from whole-body screening, and whether the benefits vary by ethnicity.”

He acknowledged certain limitations of the study, including the relatively small sample size of melanoma cases in the NCI Familial Melanoma Study and the imputation of missing melanoma-thickness data. “Additionally, since this was a prospective cohort study, we were not able to distinguish the independent effect of each intervention,” he said. “Randomized controlled studies are needed to understand the impact of each aspect of the intervention, such as whole-body screening, melanoma education, or strategies for skin protection.”

In an interview, Maryam M. Asgari, MD, professor of dermatology at Harvard University, Boston, called the analysis “well done,” but commented on the potential role of selection bias impacting the findings. “People who have a strong family history of melanoma and who are opting to engage in an NCI study and come in for full-body skin checks and go through that education process may have very different health-seeking behaviors than individuals in the general population that would be reported to SEER,” she said.

She also raised the question of whether the results were driven by the early detection through the NCI’s program of provider screening or through the educational component that enables earlier self-detection. “If you’re an individual involved in a study and that brings attention to your moles and you have a strong family history of melanoma to begin with, it is not surprising that you are going to have heightened awareness of any changing mole and therefore are more likely to have melanoma detected at an earlier stage,” Dr. Asgari said.

The study was supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics at the National Cancer Institute. Dr. Sargen reported having no financial disclosures.
Dr. Asgari disclosed that she has received research support from the Melanoma Research Alliance.
 

[email protected]