Sangmin Lee, MDMyelodysplastic syndromes (MDS) is risk stratified using the International Prognostic Scoring System (IPSS) and the revised IPSS (IPSS-R). Hypomethylating agents (HMA) are standard of care for higher risk MDS patients as well as select lower risk MDS patients. While IPSS and IPSS-R are tools used to stratify outcomes, there is no scoring system or biomarker that is utilized to predict the response to HMA. Two recent studies explore possible predictive factors for response to azacitidine. In a retrospective analysis of MDS patients treated with azacitidine in the Hellenic MDS Study Group, Eastern Cooperative Oncology Group Performance Status (ECOG) ≥2 and baseline serum ferritin (>520 ng/ml) were shown to predict response to azacitidine, independent of IPSS-R (OR 0.33, p=1.1x10-4, OR 0.54, p=0.0.013, respectively). Responders were defined by either achieving complete remission (CR), partial remission, or hematologic improvement (HI). Worse ECOG status and elevated ferritin were also associated with worse overall survival independent of IPSS-R (HR 2.03, p=2.1x10-6, HR 1.46, p=0.0005). Based on this, a modified IPSS and IPSS-R system incorporating ECOG status and serum ferritin level was developed to correlate with overall survival and leukemia free survival in patients undergoing treatment with azacitidine. The limitation of this analysis is that it is retrospective and lack of a validation cohort. Utility of incorporation of serum ferritin and ECOG status to IPSS and IPSS-R should be further investigated in a prospective study.
Higher expression of Wilms’ tumor 1 (WT-1) has been associated with poor survival in MDS. To further characterize the prognostic value of WT-1 expression level, peripheral WT-1 mRNA expression level at baseline was measured in MDS patients undergoing treatment with azacitidine. Lower WT-1 mRNA level was associated with higher overall response, as defined by CR, marrow CR, partial response, or HI (p=0.03), although WT-1 mRNA level did not show difference in overall survival. This was a small retrospective, single center study; role of WT-1 mRNA level as a biomarker for response to azacitidine should be further investigated.
Results of a multi-center trial comparing reduced intensity allogeneic stem cell transplant (SCT) to hypomethylating agents or best supportive care in higher risk MDS patients aged 50-75 was reported in the annual meeting of the American Society of Hematology in 2020. Patients with intermediate-2 or higher risk by IPSS were assigned based on SCT or no SCT arm based on donor status, and patients who had donor proceeded to reduced intensity SCT within 6 months of enrolment. In an intent-to-treat analysis, the study showed different in 3-year overall survival, which was the primary endpoint between SCT vs non-SCT arms (47.9% vs 26.6%, p=0.0001). Leukemia-free survival at 3 years was also greater for the SCT arm (35.8% vs 20.6%, p=0.003). Allogenic stem cell transplant is currently offered to patients with higher risk MDS given this is the only potential curable approach for MDS patients. This study further supports allogeneic stem cell transplant for older patients with higher risk MDS.
Author and Disclosure Information
Sangmin Lee, MD, Assistant Professor of Medicine, Division of Hematology/Oncology, Weill Cornell Medicine, New York, NY
Dr. Lee has disclosed the following relevant financial relationships: Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Helsinn; AstraZeneca; Innate Pharma; Bristol-Myers Squibb; Pin Therapeutics Received income in an amount equal to or greater than $250 from: Helsinn; AstraZeneca; Innate Pharma; Bristol-Myers Squibb; Pin Therapeutics
Sangmin Lee, MD, Assistant Professor of Medicine, Division of Hematology/Oncology, Weill Cornell Medicine, New York, NY
Dr. Lee has disclosed the following relevant financial relationships: Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Helsinn; AstraZeneca; Innate Pharma; Bristol-Myers Squibb; Pin Therapeutics Received income in an amount equal to or greater than $250 from: Helsinn; AstraZeneca; Innate Pharma; Bristol-Myers Squibb; Pin Therapeutics
Author and Disclosure Information
Sangmin Lee, MD, Assistant Professor of Medicine, Division of Hematology/Oncology, Weill Cornell Medicine, New York, NY
Dr. Lee has disclosed the following relevant financial relationships: Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Helsinn; AstraZeneca; Innate Pharma; Bristol-Myers Squibb; Pin Therapeutics Received income in an amount equal to or greater than $250 from: Helsinn; AstraZeneca; Innate Pharma; Bristol-Myers Squibb; Pin Therapeutics
Dr. Lee scans the journals, so you don't have to!
Dr. Lee scans the journals, so you don't have to!
Sangmin Lee, MDMyelodysplastic syndromes (MDS) is risk stratified using the International Prognostic Scoring System (IPSS) and the revised IPSS (IPSS-R). Hypomethylating agents (HMA) are standard of care for higher risk MDS patients as well as select lower risk MDS patients. While IPSS and IPSS-R are tools used to stratify outcomes, there is no scoring system or biomarker that is utilized to predict the response to HMA. Two recent studies explore possible predictive factors for response to azacitidine. In a retrospective analysis of MDS patients treated with azacitidine in the Hellenic MDS Study Group, Eastern Cooperative Oncology Group Performance Status (ECOG) ≥2 and baseline serum ferritin (>520 ng/ml) were shown to predict response to azacitidine, independent of IPSS-R (OR 0.33, p=1.1x10-4, OR 0.54, p=0.0.013, respectively). Responders were defined by either achieving complete remission (CR), partial remission, or hematologic improvement (HI). Worse ECOG status and elevated ferritin were also associated with worse overall survival independent of IPSS-R (HR 2.03, p=2.1x10-6, HR 1.46, p=0.0005). Based on this, a modified IPSS and IPSS-R system incorporating ECOG status and serum ferritin level was developed to correlate with overall survival and leukemia free survival in patients undergoing treatment with azacitidine. The limitation of this analysis is that it is retrospective and lack of a validation cohort. Utility of incorporation of serum ferritin and ECOG status to IPSS and IPSS-R should be further investigated in a prospective study.
Higher expression of Wilms’ tumor 1 (WT-1) has been associated with poor survival in MDS. To further characterize the prognostic value of WT-1 expression level, peripheral WT-1 mRNA expression level at baseline was measured in MDS patients undergoing treatment with azacitidine. Lower WT-1 mRNA level was associated with higher overall response, as defined by CR, marrow CR, partial response, or HI (p=0.03), although WT-1 mRNA level did not show difference in overall survival. This was a small retrospective, single center study; role of WT-1 mRNA level as a biomarker for response to azacitidine should be further investigated.
Results of a multi-center trial comparing reduced intensity allogeneic stem cell transplant (SCT) to hypomethylating agents or best supportive care in higher risk MDS patients aged 50-75 was reported in the annual meeting of the American Society of Hematology in 2020. Patients with intermediate-2 or higher risk by IPSS were assigned based on SCT or no SCT arm based on donor status, and patients who had donor proceeded to reduced intensity SCT within 6 months of enrolment. In an intent-to-treat analysis, the study showed different in 3-year overall survival, which was the primary endpoint between SCT vs non-SCT arms (47.9% vs 26.6%, p=0.0001). Leukemia-free survival at 3 years was also greater for the SCT arm (35.8% vs 20.6%, p=0.003). Allogenic stem cell transplant is currently offered to patients with higher risk MDS given this is the only potential curable approach for MDS patients. This study further supports allogeneic stem cell transplant for older patients with higher risk MDS.
Sangmin Lee, MDMyelodysplastic syndromes (MDS) is risk stratified using the International Prognostic Scoring System (IPSS) and the revised IPSS (IPSS-R). Hypomethylating agents (HMA) are standard of care for higher risk MDS patients as well as select lower risk MDS patients. While IPSS and IPSS-R are tools used to stratify outcomes, there is no scoring system or biomarker that is utilized to predict the response to HMA. Two recent studies explore possible predictive factors for response to azacitidine. In a retrospective analysis of MDS patients treated with azacitidine in the Hellenic MDS Study Group, Eastern Cooperative Oncology Group Performance Status (ECOG) ≥2 and baseline serum ferritin (>520 ng/ml) were shown to predict response to azacitidine, independent of IPSS-R (OR 0.33, p=1.1x10-4, OR 0.54, p=0.0.013, respectively). Responders were defined by either achieving complete remission (CR), partial remission, or hematologic improvement (HI). Worse ECOG status and elevated ferritin were also associated with worse overall survival independent of IPSS-R (HR 2.03, p=2.1x10-6, HR 1.46, p=0.0005). Based on this, a modified IPSS and IPSS-R system incorporating ECOG status and serum ferritin level was developed to correlate with overall survival and leukemia free survival in patients undergoing treatment with azacitidine. The limitation of this analysis is that it is retrospective and lack of a validation cohort. Utility of incorporation of serum ferritin and ECOG status to IPSS and IPSS-R should be further investigated in a prospective study.
Higher expression of Wilms’ tumor 1 (WT-1) has been associated with poor survival in MDS. To further characterize the prognostic value of WT-1 expression level, peripheral WT-1 mRNA expression level at baseline was measured in MDS patients undergoing treatment with azacitidine. Lower WT-1 mRNA level was associated with higher overall response, as defined by CR, marrow CR, partial response, or HI (p=0.03), although WT-1 mRNA level did not show difference in overall survival. This was a small retrospective, single center study; role of WT-1 mRNA level as a biomarker for response to azacitidine should be further investigated.
Results of a multi-center trial comparing reduced intensity allogeneic stem cell transplant (SCT) to hypomethylating agents or best supportive care in higher risk MDS patients aged 50-75 was reported in the annual meeting of the American Society of Hematology in 2020. Patients with intermediate-2 or higher risk by IPSS were assigned based on SCT or no SCT arm based on donor status, and patients who had donor proceeded to reduced intensity SCT within 6 months of enrolment. In an intent-to-treat analysis, the study showed different in 3-year overall survival, which was the primary endpoint between SCT vs non-SCT arms (47.9% vs 26.6%, p=0.0001). Leukemia-free survival at 3 years was also greater for the SCT arm (35.8% vs 20.6%, p=0.003). Allogenic stem cell transplant is currently offered to patients with higher risk MDS given this is the only potential curable approach for MDS patients. This study further supports allogeneic stem cell transplant for older patients with higher risk MDS.
