Article Type
Changed
Fri, 05/06/2022 - 16:22
Dr. Lee scans the journals, so you don’t have to!

Sangmin Lee, MD
Current upfront standard therapy for patients with higher risk myelodysplastic syndromes (MDS) is hypomethylating agents (HMA), either azacitidine or decitabine, while allogeneic stem cell transplant can be considered in eligible patients as a potentially curative therapy. While several studies have shown potential benefit of achieving complete remission with azacitidine prior to allogeneic stem cell transplant; a recent meta-analysis examined the role of HMA as a bridge prior to allogeneic stem cell transplant in MDS patients. From seven retrospective studies that were included in the meta-analysis, administration of HMA prior to allogeneic stem cell transplantation did not improve overall survival (OS) compared to no HMA prior to transplant (HR=0.86, p=0.32). The limitation of this meta-analysis was small study size, heterogeneity of the cohorts, retrospective nature of studies included, and disease status prior to transplantation was not factored in the analysis. HMA as a bridge to allogeneic stem cell transplant in MDS patients with persistent disease warrants further prospective investigation.

 


Human leukocyte antigen (HLA)-mismatched hematopoetic stem cell microtransplantation (MST) has previously been evaluated in AML in combination with chemotherapy and suggests potential improvement in outcomes. Li et al evaluated MST combined with decitabine in patients with intermediate or high risk MDS compared to decitabine alone.  Out of 22 patients in the study, the cohort that received MST with decitabine had higher median OS (24 vs 14.2 months, p=0.04), although there was no statistical significant difference in overall response rate. There was no reported graft vs host disease, and adverse events were similar between the two groups. The main limitation of the study was the very small sample size; further prospective studies utilizing MST in MDS are needed to demonstrate benefit.

 

MDS patients often present with neutropenia and develop worsening neutropenia due to myelosuppression from HMA therapy, resulting in increased risk of infections including invasive fungal infection (IFI). Tey et al reported a retrospective analysis of the rate of IFI in patients with MDS or low blast count AML receiving azacitidine. Out of 117 patients, 61% received antifungal prophylaxis, either with posaconazole (n=70) or voriconazole (n=1). The IFI rate was 7.7% in the cohort with median time of onset of 74 days from start of azacitidine treatment (range 1-226); the IFI rate did not differ statistically between those receiving prophylaxis vs not (5.6% vs 10.9%, p=0.30). However, presence of neutropenia at three months of treatment was associated with increased IFI risk (HR 8.29, p=0.01), and IFI was associated with increased mortality in a multivariate analysis (HR 8.37, p<0.0001). Anti-fungal prophylaxis is currently standard practice for MDS patients who present or develop neutropenia; however, HMA treatment is associated with prolonged neutropenia due to myelosuppression and time to response. A more effective therapy with less myelosuppression is needed for treatment of 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

Publications
Topics
Sections
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

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, MD
Current upfront standard therapy for patients with higher risk myelodysplastic syndromes (MDS) is hypomethylating agents (HMA), either azacitidine or decitabine, while allogeneic stem cell transplant can be considered in eligible patients as a potentially curative therapy. While several studies have shown potential benefit of achieving complete remission with azacitidine prior to allogeneic stem cell transplant; a recent meta-analysis examined the role of HMA as a bridge prior to allogeneic stem cell transplant in MDS patients. From seven retrospective studies that were included in the meta-analysis, administration of HMA prior to allogeneic stem cell transplantation did not improve overall survival (OS) compared to no HMA prior to transplant (HR=0.86, p=0.32). The limitation of this meta-analysis was small study size, heterogeneity of the cohorts, retrospective nature of studies included, and disease status prior to transplantation was not factored in the analysis. HMA as a bridge to allogeneic stem cell transplant in MDS patients with persistent disease warrants further prospective investigation.

 


Human leukocyte antigen (HLA)-mismatched hematopoetic stem cell microtransplantation (MST) has previously been evaluated in AML in combination with chemotherapy and suggests potential improvement in outcomes. Li et al evaluated MST combined with decitabine in patients with intermediate or high risk MDS compared to decitabine alone.  Out of 22 patients in the study, the cohort that received MST with decitabine had higher median OS (24 vs 14.2 months, p=0.04), although there was no statistical significant difference in overall response rate. There was no reported graft vs host disease, and adverse events were similar between the two groups. The main limitation of the study was the very small sample size; further prospective studies utilizing MST in MDS are needed to demonstrate benefit.

 

MDS patients often present with neutropenia and develop worsening neutropenia due to myelosuppression from HMA therapy, resulting in increased risk of infections including invasive fungal infection (IFI). Tey et al reported a retrospective analysis of the rate of IFI in patients with MDS or low blast count AML receiving azacitidine. Out of 117 patients, 61% received antifungal prophylaxis, either with posaconazole (n=70) or voriconazole (n=1). The IFI rate was 7.7% in the cohort with median time of onset of 74 days from start of azacitidine treatment (range 1-226); the IFI rate did not differ statistically between those receiving prophylaxis vs not (5.6% vs 10.9%, p=0.30). However, presence of neutropenia at three months of treatment was associated with increased IFI risk (HR 8.29, p=0.01), and IFI was associated with increased mortality in a multivariate analysis (HR 8.37, p<0.0001). Anti-fungal prophylaxis is currently standard practice for MDS patients who present or develop neutropenia; however, HMA treatment is associated with prolonged neutropenia due to myelosuppression and time to response. A more effective therapy with less myelosuppression is needed for treatment of MDS.

Sangmin Lee, MD
Current upfront standard therapy for patients with higher risk myelodysplastic syndromes (MDS) is hypomethylating agents (HMA), either azacitidine or decitabine, while allogeneic stem cell transplant can be considered in eligible patients as a potentially curative therapy. While several studies have shown potential benefit of achieving complete remission with azacitidine prior to allogeneic stem cell transplant; a recent meta-analysis examined the role of HMA as a bridge prior to allogeneic stem cell transplant in MDS patients. From seven retrospective studies that were included in the meta-analysis, administration of HMA prior to allogeneic stem cell transplantation did not improve overall survival (OS) compared to no HMA prior to transplant (HR=0.86, p=0.32). The limitation of this meta-analysis was small study size, heterogeneity of the cohorts, retrospective nature of studies included, and disease status prior to transplantation was not factored in the analysis. HMA as a bridge to allogeneic stem cell transplant in MDS patients with persistent disease warrants further prospective investigation.

 


Human leukocyte antigen (HLA)-mismatched hematopoetic stem cell microtransplantation (MST) has previously been evaluated in AML in combination with chemotherapy and suggests potential improvement in outcomes. Li et al evaluated MST combined with decitabine in patients with intermediate or high risk MDS compared to decitabine alone.  Out of 22 patients in the study, the cohort that received MST with decitabine had higher median OS (24 vs 14.2 months, p=0.04), although there was no statistical significant difference in overall response rate. There was no reported graft vs host disease, and adverse events were similar between the two groups. The main limitation of the study was the very small sample size; further prospective studies utilizing MST in MDS are needed to demonstrate benefit.

 

MDS patients often present with neutropenia and develop worsening neutropenia due to myelosuppression from HMA therapy, resulting in increased risk of infections including invasive fungal infection (IFI). Tey et al reported a retrospective analysis of the rate of IFI in patients with MDS or low blast count AML receiving azacitidine. Out of 117 patients, 61% received antifungal prophylaxis, either with posaconazole (n=70) or voriconazole (n=1). The IFI rate was 7.7% in the cohort with median time of onset of 74 days from start of azacitidine treatment (range 1-226); the IFI rate did not differ statistically between those receiving prophylaxis vs not (5.6% vs 10.9%, p=0.30). However, presence of neutropenia at three months of treatment was associated with increased IFI risk (HR 8.29, p=0.01), and IFI was associated with increased mortality in a multivariate analysis (HR 8.37, p<0.0001). Anti-fungal prophylaxis is currently standard practice for MDS patients who present or develop neutropenia; however, HMA treatment is associated with prolonged neutropenia due to myelosuppression and time to response. A more effective therapy with less myelosuppression is needed for treatment of MDS.

Publications
Publications
Topics
Article Type
Sections
Disallow All Ads
Content Gating
No Gating (article Unlocked/Free)
Alternative CME
Disqus Comments
Default
Article Series
Clinical Edge Journal Scan: MDS May 2021
Gate On Date
Fri, 04/02/2021 - 10:00
Un-Gate On Date
Fri, 04/02/2021 - 10:00
Use ProPublica
CFC Schedule Remove Status
Fri, 04/02/2021 - 10:00
Hide sidebar & use full width
render the right sidebar.
Conference Recap Checkbox
Not Conference Recap
Clinical Edge
Display the Slideshow in this Article
Medscape Article
Display survey writer
Reuters content
Disable Inline Native ads
WebMD Article