What are the key considerations when determining the number and duration of blinatumomab treatment cycles?

The ALL Hub was pleased to speak with Sabina Chiaretti, Sapienza University of Rome, Italy. We asked, What are the key considerations when determining the number and duration of blinatumomab treatment cycles?

During this interview, Chiaretti discusses considerations when determining the number of blinatumomab cycles to administer in B-cell acute lymphoblastic leukemia (B-ALL), including Philadelphia chromosome (Ph) status, measurable residual disease (MRD), and genomic risk. She also highlights evidence from clinical trials and ongoing studies evaluating different blinatumomab treatment schedules. 

Key points 

• The optimal number of blinatumomab cycles needed as part of the treatment of patients with B-ALL remains an area of investigation, with several factors informing the number of cycles administered, including Ph status, MRD response, and genomic features. 
• For patients with newly diagnosed Ph− B-ALL, evidence from the ECOG-ACRIN E1910 phase III trial (NCT02003222) supports the use of 4 cycles of blinatumomab in consolidation.^1-3 Further evaluation of blinatumomab in newly diagnosed Ph− B-ALL is ongoing.^4,5 The phase III GOLDEN GATE study (NCT04994717) is investigating a treatment strategy incorporating 7 cycles of blinatumomab in older adults with newly diagnosed Ph− B-ALL, which may provide further insight into the use of blinatumomab in this patient population.^4,5 
• In patients with Ph+ B-ALL, current evidence suggests that additional cycles of blinatumomab may deepen molecular responses.⁶ For example, in the D-ALBA study, molecular response rates increased with successive cycles of blinatumomab, supporting the use of multiple treatment cycles in this setting.⁶ 
• MRD response may help inform treatment duration, and achieving and maintaining MRD negativity is an important consideration when determining the number of blinatumomab cycles. In the E1910 study, in adults with newly diagnosed Ph− B-ALL who achieved MRD-negative remission after initial treatment, the addition of 4 cycles of blinatumomab to consolidation was associated with improved 3-year overall survival (85% vs 68%; p = 0.002) and relapse-free survival (80% vs 64%) compared with chemotherapy alone.³ 
• Genomic characteristics may also be relevant when considering treatment strategies; advances in genomic and transcriptomic testing have identified molecular subgroups of B-ALL with differing disease characteristics, including Ph-like, MEF2D-rearranged, and KMT2A-rearranged subsets.⁷ 
• Overall, the available evidence supports the use of blinatumomab across different ALL settings, while ongoing studies continue to explore optimal treatment schedules and duration.

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