2020 ASH Annual Meeting
NEWS
The 62nd American Society of Hematology ( ASH ) Annual Meeting & Exposition , which was held virtually December 5-8 , 2020 , featured practice-changing research from across the spectrum of blood diseases .
In this issue , ASH Clinical News concludes its coverage of the meeting . For more reporting from the annual meeting , see the “ Focus on Lymphoid & Plasma Cell Malignancies ” supplement .
Researchers Recommend New Processes for Bone Marrow Screening for HLH
For patients suspected of having hemophagocytic lymphohistiocytosis ( HLH ), bone marrow biopsy is often used to identify the presence of hemophagocytosis and assess for underlying malignancy . However , while bone marrow biopsy is an easily accessible test , there currently are no evidence-based guidelines on the reporting of hemophagocytosis on bone marrow biopsy , noted Caroline Wilson , MBBS , from Canberra Hospital in Australia . There also are no reports of a correlation between hemophagocytosis with the clinical diagnostic criteria for HLH ( HLH-2004 ).
In this study , Dr . Wilson and colleagues aimed to determine if the amount of hemophagocytosis identified in the bone marrow biopsy correlated with HLH-2004 diagnostic criteria and to determine the extent of interobserver variability in reporting hemophagocytosis . Two hematopathologists independently reviewed bone marrow biopsies from adults who were under investigation for HLH . Hematopathologists were blinded to the original biopsy report . Specimens were categorized according to the average number of actively hemophagocytic cells in each slide ( 0 , 1 , 2-4 , or ≥5 ). If there was discordance pertaining to the degree of hemophagocytosis in a given sample , the sample was reviewed by both assessors to reach a consensus .
A total of 62 specimens from 59 patients were available for assessment . An underlying hematologic condition was identified in 34 cases ( 58 %). The most common condition was lymphoma , found in 15 cases ( 25 %).
Dr . Wilson and colleagues found a significant association between the amount of hemophagocytosis identified on the aspirate samples and the number of HLH-2004 criteria met ( p < 0.05 ). Hemophagocytosis was present on 31 samples , and there was a significant correlation between the a- mount of hemophagocytosis and ferritin levels ( p < 0.05 ).
Notably , interobserver variability was present in a substantial portion of cases ( 63 %).
Based on these observations , the authors formulated recommendations for reporting of hemophagocytosis in bone marrow specimens , including :
• Count only macrophages ingesting intact hemopoietic cells .
• Quantify the average number of active histiocytes per aspirate slide .
• Count histiocytes away from particles where the cellular outline is clear .
• Avoid counting conglomerates of histiocytes where the cellular margins are indistinct .
• On the aspirate specimen , assess for hemophagocytosis on both the trail and squash preparations .
• Delineating hemophagocytosis on trephine samples is difficult without the use of a CD68 immunohistochemical stain .
These recommendations , Dr . Wilson and authors noted , could help to reduce interobserver variability on the reporting of hemophagocytosis .
Study authors report no relevant conflicts of interest .
Reference Wilson C , Lee W , Cook M , et al . Correlation of hemophagocytosis with clinical criteria of hemophagocytic lymphohistiocytosis and recommendations for screening bone marrow samples in adult patients . Abstract # 2645 . Presented at the 2020 American Society of Hematology Annual Meeting , December 7 , 2020 .
Roxadustat Superior to Epoetin Alfa in Patients With Anemia and Dialysis-Dependent Chronic Kidney Disease
In patients with anemia and dialysis-dependent chronic kidney disease ( CKD ), treatment with roxadustat led to higher hemoglobin ( Hb ) levels and a reduced need for red blood cell ( RBC ) transfusions , compared with treatment with epoetin alfa ( EPO ), according to research conducted by Steven Fishbane , MD , of the Feinstein Institutes for Medical Research at Northwell Health in New York and presented as part of the 2020 ASH Annual Meeting .
The investigators also found that roxadustat reduced the risk of major adverse cardiovascular events ( MACE ), including death , myocardial infarction , and stroke , in patients who were enrolled within four months of beginning dialysis .
Erythropoiesis-stimulating agents ( ESAs ) such as EPO are the current standards of care for anemia in patients with CKD who are on dialysis , with or without intravenous iron supplementation and RBC transfusion . However , because of potential cardiotoxicity associated with ESAs , patients may receive less-than-optimal doses , leading to increased need for RBC transfusions , researchers explained .
Roxadustat is an oral hypoxia – inducible factor prolyl hydroxylase inhibitor that regulates erythropoiesis and iron metabolism . To compare the efficacy of this newer agent with the EPO standard-of-care , the investigators conducted a pooled analysis of three phase III trials , the global ROCKIES and HIMALAYAS trials and the U . S . -only SIERRAS trial , each of which evaluated the safety and efficacy of roxadustat against EPO .
Across the trials , a total of 3,890 patients requiring dialysis and anemia treatment were randomized to either roxadustat ( n = 1,943 ) or EPO ( n = 1,947 ). Mean ages were 54.3 years in the roxadustat group and 55.2 years in the EPO group . Mean baseline Hb levels were similar in each arm ( 9.6 and 9.7 g / dL ).
In the pooled analysis , the primary endpoint ( defined as the average change in Hb from baseline to weeks 28-52 ) was met in each individual study , with roxadustat either performing as noninferior or superior to EPO . In the pooled analysis , the mean change in Hb from baseline was 1.22 g / dL in patients receiving roxadustat , compared with 0.99 g / dL in patients randomized to EPO ( p < 0.001 ).
Patients who received roxadustat also received fewer transfusions than those in the EPO group : 9.5 % versus 12.8 %, respectively ( hazard ratio [ HR ] = 0.82 ; p = 0.997 ).
Roxadustat also was effective regardless of patients ’ inflammation status ( determined by elevated C-reactive protein levels ). Mean Hb increases in this subset of patients were 1.27 g / dL in the roxadustat group versus 1.05 g / dL in the EPO group ( p < 0.001 ).
To review the cardiovascular safety of roxadustat with EPO , the authors reviewed time to first MACE and MACE plus heart failure or unstable angina requiring hospitalization . Comparing roxadustat with EPO , rates of MACE were similar between the treatment arms ( HR = 0.96 ); a similar relationship was observed for MACE plus other cardiovascular events ( HR = 0.86 ).
The researchers also looked at outcomes in 1,526 patients who had been on dialysis for less than four months and found that patients who received roxadustat had a 30 % lower risk of MACE and a 34 % lower risk of MACE plus other cardiovascular events .
According to these safety and efficacy findings , roxadustat could offer a new oral treatment option for patients living with CKD and anemia , the researchers concluded .
Study authors report relationships with FibroGen and AstraZeneca , which sponsored this trial .
Reference Fishbane S , Provenzano R , Szczech L , et al . Pooled efficacy and cardiovascular safety results of roxadustat compared with epoetin alfa in the treatment of anemia in chronic kidney disease patients on dialysis . Abstract # 749 . Presented at the 2020 American Society of Hematology Annual Meeting , December 5 , 2020 .
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