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DLIs were injected in 17 patients : Five patients received one DLI , two patients received two DLIs , and eight patients received all three planned DLIs . Two patients received additional DLIs because of persistent mixed chimerism .
Four months following transplantation , 24 patients ( 80 %) demonstrated full donor chimerism (> 95 %) in CD3 + cells . Nine patients developed grade 1-3 aGVHD ( CI 29.8 ± 9 ), six of whom did not receive DLI and three following DLI . No grade 4 aGVHD was observed . Nine patients developed chronic GVHD , three of whom did not receive DLI and six following DLI .
The median follow-up from alloHCT of 36 months ( range = 12-46 months ). The median time to relapse was 5 months ( range = 2.5-9 months ), and the cumulative incidence of relapse at 3 years was approximately 28 percent .
These results suggest that azacitidine and DLI may have utility as a prophylactic treatment to reduce the risk of post-transplant relapse . The incidence of GVHD following azacitidine plus DLI was not “ overwhelming ,” the authors concluded .
This study is limited by its small patient population and lack of a control group .
Reference
Guillaume T , Yakoub-Agha I , Tabrizi R , et al . Prospective phase II study of prophylactic azacitidine and donor lymphocyte infusions following allogeneic hematopoietic stem cell transplantation for high risk acute myeloid leukemia and myelodysplastic syndrome . Oral abstract presented at the 43rd Annual Meeting of the European Society for Blood and Marrow Transplantation , March 28 , 2017 ; Marseilles , France .
SWOG S1203 : Comparing Standards of Care for Acute Myeloid Leukemia
Investigators from the phase III US Intergroup SWOGled S1203 trial reported that remission induction with 7 + 3 chemotherapy ( cytarabine plus daunorubicin ) should remain the standard of care for younger patients with acute myeloid leukemia ( AML ). In addition , the researchers were able to increase the proportion of patients with high risk acute myeloid leukemia ( AML ) who proceeded to allogeneic hematopoietic cell transplantation ( alloHCT ) in first remission , which may significantly increase the likelihood of relapse-free survival ( RFS ).
7 + 3 Still Standard of Care In the first analysis , Guillermo Garcia-Manero , MD , from the University of Texas MD Anderson Cancer Center in Houston , and cooperative group clinical investigators evaluated whether adding the histone deacetylase ( HDAC ) inhibitor vorinostat to a regimen of idarubicin and high-dose cytarabine , or using high-dose cytarabine during induction instead of standard-dose cytarabine , could improve event-free survival ( EFS ; the study ’ s primary endpoint ) over standard 7 + 3 . 1
“ A phase II study of vorinostat plus idarubicin and HDAC induction demonstrated an overall response rate of 85 percent and a 4 percent induction mortality rate ,” Dr . Garcia-Manero said during his presentation of the results . “ We hypothesized that the addition of vorinostat to idarubicin plus HDAC is superior to 7 + 3 in younger patients with AML .”
The SWOG S1203 trial enrolled 738 patients with previously untreated AML who had preserved cardiac function and no severe comorbidities . Participants ’ median age was 49 years ( range = 18-60 years ), and most ( 75 %) were between 40 and 60 years of age .
Patients were randomly assigned to one of three treatment arms : 7 + 3 ( n = 261 ), idarubicin and high-dose cytarabine ( IA ; n = 261 ), or IA plus vorinostat ( IA + V ; n = 216 ).
Most patients had intermediate-risk cytogenetics ( 63 %), while
13 percent had favorable cytogenetics and 22 percent had highrisk cytogenetics . Among patients with known mutations , the most common was FLT3 ( 21 %), followed by NPM1 ( 20 %). Induction and consolidation treatment in each arm consisted of :
• 7 + 3 arm : Daunorubicin 90 mg / m 2 once daily on days 1-3 plus cytarabine 100 mg / m 2 continuous infusion on days 1-7 , followed by consolidation with cytarabine 3 g / m 2 every 12 hours on days 1 , 3 , and 5
• IA arm : Idarubicin 12 mg / m 2 once daily on days 1-3 plus cytarabine 1.5 g / m 2 continuous infusion on days 4-7 during induction , followed by consolidation with idarubicin 8 mg / m 2 once daily on days 4-5 plus cytarabine 0.75 g / m 2 continuous infusion on days 4-6
• IA + V arm : IA plus vorinostat 500 mg thrice daily on days 1-3 of induction and consolidation
Contrary to what investigators hypothesized , neither IA nor IA + V was superior to 7 + 3 on all survival endpoints , including EFS , RFS , and overall survival ( OS ). “ The arms were all neutral ,” Dr . Garcia-Manero reported . “ There was no evidence of superiority in the high-dose induction group or the high-dose induction plus vorinostat group .”
Rates of complete remission ( CR ) also were similar among all three treatment arms : 75 percent for 7 + 3 , 79 percent for IA , and 77 percent for IA + V ( p = 0.58 ).
There were no differences in outcomes for any standard-risk group ; however , in patients with favorable cytogenetics , outcomes were significantly better with 7 + 3 than with IA or IA + V , which the authors suggest is related to the use of lower doses of cytarabine during post-remission therapy .
The rates of adverse events ( AEs ) were similar among all
22 Focus on Myeloid Malignancies