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Bortezomib combined with pediatric AML chemotherapy
1 0.75 0.5 0.25 0
Figure 2. Event-free survival (EFS) and overall survival (OS) by treatment arm.
Several limitations of this clinical trial require acknowl- edgment. First, correlative biology data on the unfolded protein response and other biomarkers of bortezomib effi- cacy are currently ongoing and thus could not be included in this report. These ongoing studies may define subgroup populations who may benefit from bortezomib.25 Second, comprehensive molecular profiling of each individual AML case is ongoing but is still not complete.26 The com- pletion of this work will likely enable the next generation of risk prediction and therapy individualization. Finally, the ongoing analyses of changes in chemotherapy course sequence and use of allogeneic donor SCT will face the well documented challenges of limitations in chemothera- py toxicity reporting,27,28 and the challenges faced by all co- operative oncology groups to collect and account for vari- able supportive care practices and particular factors at the level of each individual center that may impact treatment outcomes.
In conclusion, the AAML1031 trial demonstrates that bortezomib can be combined safely with standard pedi- atric AML chemotherapy but that this combination does
not improve EFS or OS and is associated with increased toxicity. Thus, these data do not support the use of borte- zomib in pediatric AML therapy at this time. Despite this, the successful conduct of this very complex trial highlights the clinical trial capabilities of COG in partnership with the CTEP, and may serve as a paradigm for definitive effi- cacy clinical trials initiated in the setting of limited prelim- inary data. Finally, the AAML1031 clinical trial data set, in conjunction with ongoing biology studies, will serve as an invaluable data platform for future clinical and translation- al investigations.
Acknowledgments
The AAML1031 study team would like to acknowledge the patients and families who participated in the AAML1031 clinical trial.
Funding
This research was supported by NCTN Operations Center Grant (U10CA180886) and NCTN Statistics & Data Center Grant (U10CA180899).
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