Table 5:

Benefit-Risk Assessment

Dimension	Evidence and Uncertainties	Conclusions and Reasons
Analysis of Condition	The expected survival of patients with untreated newly diagnosed or relapsed BCP ALL is weeks.	BCP ALL is a fatal disease.
Current Treatment Options	The current standard of care for treatment of newly diagnosed or relapsed Ph-negative BCP ALL with curative intent is intensive multiphasic combination chemotherapy including at least induction and consolidation. With treatment for newly diagnosed disease, the survival is about 50% for adults and 85% for pediatric patients. With treatment with curative intent for relapsed disease, the survival is about 10% for adults and 50% for pediatric patients.	New treatments are needed to improve survival of patients with Ph-negative BCP ALL.
Benefit	E1910 was a randomized trial comparing chemotherapy alone to chemotherapy plus blinatumomab as consolidation in adults with new diagnosed Ph-negative BCP ALL. In the population identified as “MRD-negative”, the OS HR was 0.42 (95% CI: 0.24, 0.75; p=0.003). 20120215 was a randomized trial comparing chemotherapy vs blinatumomab as the third cycle of consolidation in pediatric patients with high risk first relapse of Ph-negative BCP ALL. The OS HR was 0.35 (95% CI: 0.17, 0.70). In a study-level meta-analysis of 6 comparisons from 4 trials for Ph-negative BCP ALL, the OS HR was 0.46 (95% CI: 0.33, 0.64), and the treatment effect was consistent across disease status and trial design. Although there was substantial heterogeneity in these trials, the results are considered supportive.	Use of blinatumomab was associated with a survival advantage when used in consolidation for the regimens employed in E1910 and 20120215 for treatment of Ph-negative BCP ALL.
Risks and Risk Management	The overall safety profile in patients treated with blinatumomab in consolidation was similar to that seen in patients with MRD-positive ALL or with advanced ALL treated with blinatumomab. While efficacy could be extrapolated across age groups, safety was supported by extant data available for patients at least 1 month old.	The safety profile of blinatumomab is acceptable for the intended population. Serious risks can be managed with labeling.

Source: FDA Analysis