Literature Scan
• observation only
• tranexamic acid 1 g administered 3 times daily
• DDAVP 0.3 μg / kg ( at a maximum of 27 μg )
• clotting factor concentrate
The DDAVP option was not considered for patients with low VWF who were older than 55 years , per the study ’ s institutional policy .
Seventeen procedures were not covered with any tranexamic acid or DDAVP prophylaxis . While patients in this cohort accounted for only 11 % of the total cohort , they accounted for 33 % of the total bleeding complications observed .
Among the 71 patients with low VWF who completed DDAVP trials , the researchers noted an “ excellent and sustained ” VWF response .
The median plasma VWF : Ag levels at one and four hours after DDAVP infusion were 167 IU / dL and 130 IU / dL , respectively . In addition , the median VWF : RCo levels were 160 IU / dL at one hour and 117 IU / dL at four hours following DDAVP . “ These data confirm that DDAVP administration triggers significant secretion of endogenous VWF stores that effectively corrects plasma VWF antigen and activity levels in patients with low VWF ,” they explained .
The use of DDAVP in these patients was effective for the prevention of bleeding in minor and major elective procedures , Dr . Doherty and coauthors concluded . In addition , treatment with DDAVP was associated with bleeding prevention among patients with significant bleeding histories .
Treatment with tranexamic acid monotherapy was also effective for the prevention of bleeding in patients with low VWF who underwent non-dental minor procedures . The authors noted that these patients often received tranexamic acid because they were considered too old to receive DDAVP . Bleeding complications were reported in three of the 40 elective procedures covered with tranexamic acid alone . All bleeding complications that occurred with tranexamic acid monotherapy occurred in patients who underwent the dental intervention , the authors added .
“ Cumulatively , these findings highlight the fact that adult patients who satisfy clinicopathological criteria for a low VWF diagnosis may still have a bleeding risk even if basal VWF levels have risen above 50 IU / dL ,” Dr . Doherty and coauthors concluded . However , limitations of this study included its retrospective nature , as well as the small sample size , which may limit the generalizability of the results . According to the investigators , the small sample size warrants future adequately powered studies that can offer more robust evidence to guide optimal treatment strategies for patients with low VWF levels .
Study authors report no relevant conflicts of interest .
Reference Doherty D , Lavin M , O ’ Sullivan JM , et al . Management of elective procedures in low von Willebrand factor patients in the LoVIC study . J Thromb Haemost . 2020 December 21 . [ Epub ahead of print ]
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Can Adding Lenalidomide to Rituximab-MiniCHOP Improve Survival in Older Patients With Diffuse Large B-Cell Lymphoma ?
In a phase III trial of patients age 80 or older with diffuse large B-cell lymphoma ( DLBCL ), attempts to improve on the standard approach of rituximab plus an attenuated dose of chemotherapy ( R-miniCHOP ; cyclophosphamide , doxorubicin , vincristine , prednisone ) by adding lenalidomide were unsuccessful . However , the authors were able to find risk factors that identified patients who would have poorer overall survival ( OS ), independent of the International Prognostic Index ( IPI ) or other scoring systems .
The findings were published in the Journal of Clinical Oncology by Lucie Oberic , MD , from the Institut Universitaire du Cancer of Toulouse-Oncopole in France .
“ To the best of our knowledge , [ the SENIOR trial is ] the first randomized phase III study dedicated to patients with DLBCL ... over [ age ] 80 ,” the authors wrote . “ In this challenging setting , we have proven that a larger prospective study is possible .”
The SENIOR trial randomized 249 older patients with untreated DLBCL to receive either :
• R-miniCHOP ( n = 127 )
• lenalidomide plus R-miniCHOP ( R2-miniCHOP ; n = 122 )
Following a pre-phase treatment of vincristine and prednisone , treatment was administered in 21-day cycles for six cycles . In the R2-miniCHOP group , lenalidomide was given at a dose of 10 mg once daily on days one to 14 every three weeks .
The median age across the entire population was 83 years ( range = 80-96 ). Of patients who were classified according to immunohistochemistry , 45 % had a germinal center B-cell – like subtype ( 40 % in the R-miniCHOP group and 50 % in the R2-miniCHOP group ).
During just over 25 months of follow-up , approximately 80 % and 86 % of patients received all six planned cycles of R-miniCHOP and R2-miniCHOP arms , respectively . In the R2-miniCHOP group , 20 patients ( 17 %) required a lenalidomide dose reduction ; the majority of these instances ( n = 17 ; 85 %) were due to adverse events ( AEs ).
Overall , the primary endpoint of OS was not significantly different between the two treatment arms , with a 2-year OS of 66 % in the R-miniCHOP group and 65.7 % in the R2-miniCHOP group ( hazard ratio [ HR ] = 0.99 ; p = 0.98 ).
Rates of two-year progression-free survival were also similar with each regimen : 56.2 % and 54.8 % ( HR = 1.027 ; p = 0.89 ). There also were no significant differences in survival when looking specifically at DLBCL subtype , the investigators added .
“ In this trial , we failed to reject the null hypothesis ,” the researchers reported , offering several potential explanations . “ The proposed treatment regimen might not be adequate and brings insufficient doses of lenalidomide to the patient ,” they wrote . “ In this category of very elderly patients the dose of 10 mg once daily [ on days 1-14 , or 140 mg / cycle ] has been proposed and is accompanied by significant additional toxicity , suggesting that a higher dose would probably not have been properly tolerated .”
In the safety population , which included 241 participants , 70 % of those who received R-miniCHOP and 86 % of those who received additional lenalidomide experienced an AE . Lenalidomide treatment also was associated with a higher incidence of grade 3 / 4 AEs ( 83 %) compared with R-miniCHOP ( 74 %). The most common grade 3-4 AEs included neutropenia ( 18 % with R-miniCHOP and 35 % with R2-miniCHOP ), infections ( 8 % and 13.5 %), and anemia ( 5 % and 9 %).
When the researchers conducted a multivariate analysis to detect factors that could predict clinical outcome , they identified albuminemia < 35 g / L as the only component predictive of OS . Identification of these potential factors “ makes it possible to identify the most fragile patients for whom standard chemotherapy based on immunochemotherapy does not seem to be adequate , even after a pre-phase has been performed in all patients ,” they concluded . Along with staging , albuminemia is the most significant factor , independent of the IPI , MNA score , or IADL scale .
However , the researchers cautioned that “ the very high number of toxicities and comorbidities inherent to this population may lead to negating the beneficial effect of this experimental drug even if the dose intensity of R-miniCHOP received was equivalent in both arms .” ●
Study authors report relationships with Celgene and Roche , which supported this trial .
Reference Oberic L , Peyrade F , Puyade M , et al . Subcutaneous rituximab-miniCHOP compared with subcutaneous rituximab-miniCHOP plus lenalidomide in diffuse large B-cell lymphoma for patients age 80 years or older . J Clin Oncol . 2021 January 14 . [ Epub ahead of print ]
34 ASH Clinical News March 2021