Dr Duvall on Unanswered Questions Regarding the Optimal Role for Blinatumomab in B-ALL

"[Adding blinatumomab to chemotherapy as consolidation] makes a huge impact [on outcomes] and there is potentially an incredible benefit to using it, but we don't know the exact patient population that will truly benefit from it."

Adam DuVall, MD, MPH, assistant professor, medicine, pediatrics, University of Chicago Medicine, discusses the impact of blinatumomab (Blincyto) on the B-cell acute lympholastic leukemia (ALL) treatment paradigm, and remaining questions regarding its optimal use in the frontline setting.

The integration of blinatumomab into frontline treatment approaches for B-ALL has become increasingly common, though several unanswered questions remain regarding its optimal use, Duvall begins. The phase 3 ECOG ACRIN E1910 study (NCT02003222) evaluated the addition of blinatumomab as consolidation to chemotherapy in patients 30 to 70 years of age with newly diagnosed B-ALL who achieved a complete remission following induction chemotherapy, but representation was limited among those 30 to 40 years of age and those over 55 years of age, he notes. Notably, data from this study supported the June 2024 FDA approval of blinatumomab for the treatment of adult and pediatric patients aged 1 month or older with CD19-positive, Philadelphia chromosome–negative, B-cell precursor ALL in the consolidation phase, irrespective of measurable residual disease (MRD) status.

Although patients 40 to 55 years of age should generally receive blinatumomab in the frontline setting, it remains unclear whether certain individuals within this age group derive enough benefit from the agent, Duvall says. Notably, no clear benefit was observed with blinatumomab in the older cohort; however, the study lacked statistical power to confirm this finding, Duvall details.

Another key question is whether some patients with MRD-negative disease truly require consolidation blinatumomab, Duvall continues. Current data suggest that deeper MRD negativity, as detected by next-generation sequencing (NGS) with a sensitivity of 10⁻⁶, may help distinguish patients who may not require escalated therapy with the addition of consolidation blinatumomab, he adds.

Most ALL treatment centers do not use the E1910 regimen as their standard backbone, leading to challenges in extrapolating data when adding blinatumomab to other regimens, Duvall states. Pediatric-based approaches, which incorporate more asparaginase and intensive chemotherapy, often introduce blinatumomab without randomized data supporting its use in these settings, he explains. Similarly, pediatric patients with high-risk disease are receiving blinatumomab in some protocols without clear evidence to define its benefit in this population, Duvall notes. Ultimately, blinatumomab has demonstrated a significant impact on outcomes, but the precise patient populations that will derive the greatest benefit remain to be fully elucidated, Duvall concludes.